Read Specialty/Injectable Pharmacy Prior Authorization Criteria - Pharmacy - First Choice - Select Health of South Carolina text version

SELECT HEALTH SPECIALTY/INJECTABLE PHARMACY PRIOR AUTHORIZATION CRITERIA MAY 2012

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA ACTHAR H.P. (corticotrophin) Vials: 80u/ml available in 5 ml vials Formulary Status: Non-Formulary PA CRITERIA FOR DIAGNOSTIC TESTING FOR ADRENOCORTICAL FUNCTION · Documented trial and failure or documented medical reason for why the patient can not use generic cosyntropin. If all of the above conditions are met, the request will be approved for up a one time use; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR INITIAL APPROVAL FOR INFANTILE SPASMS aka WEST SYNDOME: · The medication is being prescribed by a pediatric neurologist and/or neurologist. · Documented trial and failure or documented medical reason for why the patient can not use one of the following therapeutic options: generic Topamax, generic Lamictal, prednisone or another corticosteroid (IV, IM or orally), a benzodiazepine, or Sabril (vigabartin). · Documentation of the patient's current weight (in kg) and height/length (in cm) or body surface area (BSA) If all of the above conditions are met, the request will be approved for one vial for a 1 month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR ALL FDA APPROVED CONDITIONS AND INDICATIONS: · Documented trial and failure or documented medical reason for why the patient can not use a generically available corticosteroid (either IV, IM, &/or orally). &/or · There is no formulary or plan preferred medication alternatives, OR there is a documented medical reason (i.e. medical intolerance, treatment failure, etc.) for why up to three formulary or plan preferred medication couldn't be used to treat the member's condition. · If all of the above conditions are met, the request will be approved for up a one time use; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. INDICATIONS: H.P. Acthar Gel is indicated: · As monotherapy for the treatment of infantile spasms in infants and children under 2 years of age. · For the treatment of acute exacerbations of multiple sclerosis in adults. · As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in: Psoriatic arthritis, Rheumatoid arthritis, Juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy), Ankylosing spondylitis. · During an exaverbation or as maintenance therapy in selected cases of: systemic lupus erythematosus, systemic dermatomyosistis (polymyositis). · Other indications where Acthar could be considered for treatment include: Dermatologic Diseases (i.e. severe erythema multiforme, stevens-johnson syndrome), allergic states (serum sickness), respiratory diseases (symptomatic sarcoidosis), edematous state (to induce a diuresis or a remission of proteinuria in the nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus), & ophthalmic diseases (i.e. those involving the eye and its adnexa such as: keratitis, iritis, iridocyclitis, diffuse posterior uveitis and chorodidits, optic neuritis, chorioretinits; anterior segment inflammation). DOSAGE AND ADMINISTRATION: Infantile Spasms in Infants and Children under 2 years of age: · Acthar Gel must be administered intramuscularly. The recommended regimen is a daily dose of 150 2 2 U/m (divided into twice daily IM injections of 75 U/m ) administered over a 2 week period. The dose should then be gradually tapered over a 2 week period. The following is one suggested tapering 2 2 schedule: 30 U/m2 in the morning for 3 days; 15 U/m in the morning for 3 days; 10 U/m in the morning 2 for 3 days; and 10 U/m every other morning for 6 days. · For calculation of body surface area, use the following formula:

o

BSA (m2) = [(weight(kg) x height (cm))/3600]

Acute Exacerbations in Adults with Multiple Sclerosis: · The recommended dose in is daily IM or SQ doses of 80-120 units for 2-3 weeks for acute exacerbations. For all other indications for adults and children over 2 years of age · The usually dose of H.P. Acthar Gel is 40-80 units given IM or SQ every 24-72 hours · Dosage should be individualized according to the disease under treatment and the general medical condition of each patient. Frequency and doe of the drug should be determined by considering severity of the disease and the initial response of the patient. ADDITIONAL INFORMATION: There are no published articles evaluating the use of ACTH gel compared to use of corticosteroids in corticosteroid-responsive conditions. The use of ACTH gel also has the potential to cause more adverse effects than corticosteroids. Given the lack of comparative data and increased risk to the patient, the clinical need to use ACTH gel for corticosteroid-responsive conditions has not been demonstrated. Unless there are medical contraindications or intolerance to corticosteroids, PHP considers the use of ACTH gel in the following steroidresponsive clinical situations not medically necessary including, but not limited to the following:

· · · · · · ·

Endocrine (nonsuppurative thyroiditis, hypercalcemia associated with cancer) Nervous system Respiratory diseases (e.g. Loeffler's syndrome) Hematologic disorders (e.g., acquired autoimmune hemolytic anemia) Neoplastic diseases (e.g., palliative treatment of leukemias and lymphomas in adults, acute leukemia of childhood) Gastrointestinal diseases (e.g., ulcerative colitis, regional enteritis) Miscellaneous (e.g., tuberculous meningitis, trichinosis with neurologic or myocardial involvement)

REFERENCES: 1. Mackay MT, Weiss SK, Adams-Webber S, et al. Practice Parameter: Medical Treatment of Infantile Spasms: Report of the American Academy of Neurology and the Child Neurology Society. Neurology 2004; 62: 1668-81. 2. Carmant, Loinel. Infantile Spasms: West Syndrome. Arch Neurol 2002; 59: 317-18. 3. Oguni H, Funatsuka M, Sasaki K, et al. Effect of ACTH Therapy for Epileptic Spasms without Hypsarrhythmia. Epilepsia 2005; 46(5): 709-15. 4. Zou LP, Ding CH, Fang F, et al. Prospective Study of First-choice Topiramate Therapy in Newly Diagnosed Infantile Spasms. Clin Neuropharmacology 2006; 29: 343-49. 5. Mikati MA, Lepejian GA, Holmes GL. Medical Treatment of Patients with Infantile Spasms. Clin Neuropharmacology 2002; 25(2): 61-70. 6. Baram TZ, Mitchell WC, Tournay A, et al. High-dose Corticotropin (ACTH) Versus Prednisone for Infantile Spasms: A Prospective, Randomized, Blinded Study. Pediatrics 1996; 97: 375-79. 7. H.P. Acthar Gel. Prescribing Information. Questcor Pharmaceuticals, Inc. October 2010. Revision/Review Date: 1/2011 Associated Policy: Prior Authorization of Medications 236.20 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA

TM AMPYRA (dalfampridine): 10 mg tablets, extended-release Formulary Status: Non-Formulary requiring prior authorization

PA CRITERIA FOR INITIAL AUTHORIZATION FOR USE IN MULTIPLE SCLEROSIS (MS): · Documentation submitted indicates that the member is an adult (18 y/o) and has a clinical diagnosis of multiple sclerosis. · Baseline diagnostic and/or clinical documentation was submitted (e.g. 12-item MS walking scale, timed 25-foot walk, Ashworth score for spasticity, lower extremity manual muscle test, quality of life etc.) that documents member's baseline walking dysfunction · For patients who have a clinical diagnosis of relapsing remitting multiple sclerosis (RRMS) or secondary progressive multiple sclerosis (SPMS) then that patient has documented (consistent with pharmacy claims data OR for new members to the health plan consistent with medical chart history) adequate trial (including dates, doses of 6 months or more of each therapy) of Avonex® (Interferon beta-1b), Betaseron® (Interferon beta-1b), Copaxone® (glatiramer acetate), Extavia® (Interferon beta-1b), Rebif® (Interferon beta-1a), or has a some other documented medical reason (intolerance, hypersensitivity, etc) for not utilizing one of these therapies to manage their medical condition. · AMPYRA is being prescribed or recommend by a neurologist at an FDA-approved dosage If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR REAUTHORIZATION FOR USE IN MS: · Diagnostic or clinical documentation was submitted (e.g. 12-item MS walking scale, timed 25-foot walk, Ashworth score for spasticity, lower extremity manual muscle test, quality of life etc.) indicating that member has demonstrated improvement in walking while receiving AMPYRA therapy · AMPYRA is being prescribed or recommend by a neurologist at an FDA-approved dosage If all of the above conditions are met, the request will be approved for up to a 12-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR INITIAL AUTHORIZATION FOR USE IN OTHER MEDICALLY ACCEPTED INDICATIONS: · The medication is recommended and prescribed by a specialist in the member's disease state · The medication is prescribed for a medically accepted use at a medically accepted dose per the medical compendia (i.e. Micromedex, Drug Points, AHFS drug information) as defined by the Social Security Act · Documentation was submitted indicating that the member has a documented (consistent with pharmacy claims data) adequate trial (including dates, doses of medications) of all first line medical therapies as recommended by the medical compendia and standard of care guidelines and/or has a documented medical reason (i.e. intolerance, contraindications, etc.) for not receiving or trying all first line medical treatment(s) If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR RE-AUTHORIZATION FOR USE IN OTHER MEDICALLY ACCEPTED INDICATIONS: · The medication is recommended or prescribed by a specialist in the member's disease state · Diagnostic and/or clinical documentation was submitted (e.g. improved disease activity index, quality of life, blood work, radiographic evidence) that indicates the member has significantly clinically benefited from receiving AMPYRA therapy · The medication is prescribed for a medically accepted use at a medically accepted dose per the medical compendia (i.e. Micromedex, Drug Points, AHFS drug information) as defined by the Social Security Act. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. FDA INDICATIONS: Multiple Sclerosis: AMPYRA (dalfampridine) is a potassium channel blocker indicated to improve walking in patients with multiple sclerosis (MS). This was demonstrated by an increase in walking speed.

The use of AMPYRA is contraindicated in the following conditions: history of seizure, moderate or severe renal impairment (CrCl 50 mL/minute). DOSAGE AND ADMINISTRATION: The maximum recommended dose of AMPYRA is one 10 mg tablet twice daily, taken with or without food, and should not be exceeded. Doses should be taken approximately 12 hours apart. Patients should not take double or extra doses if a dose is missed. No additional benefit was demonstrated at doses greater than 10 mg twice daily and adverse reactions and discontinuations because of adverse reactions were more frequent at higher doses. REFERENCES: 1. 2. 3. 4. Fischer JS, Jak AJ, Kniker JE, Rudick RA et al. Multiple sclerosis functional composite administration and scoring manual. National Multiple Sclerosis Society, Oct 2001. Hobart JC, Riazi A, Lamping DL, Fitzpatrick R. Measuring the impact of MS on walking ability. Neurology 2003;60:31-36. Katz RT. Spasticity. In: O'Young B, Young MA, Stiens SA. PM&R Secrets. Ed. Sara J Cuccurullo, MD. Philadelphia; Hanley & Belfus, 1997. Goodman AD, Brown TR, Krupp LB, Schapiro RT, Schwid SR, Cohen R, Marinucci LN, Blight AR; Fampridine MS-F203 Investigators. Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet. 2009 Feb 28;373(9665):732-8. Kachuck NJ. Sustained release oral fampridine in the treatment of multiple sclerosis. Expert Opin Pharmacother. 2009 Aug;10(12):2025-35. Thompson A, Polman C. Improving function: a new treatment era for multiple sclerosis? Lancet. 2009 Feb 28;373(9665):697-8. Bever CT, Judge SI. Sustained-release fampridine for multiple sclerosis. Expert Opin Investig Drugs. 2009 Jul;18(7):1013-24. Goodman AD, Brown TR, Cohen JA, Krupp LB, Schapiro R, Schwid SR, Cohen R, Marinucci LN, Blight AR; Fampridine MS-F202 Study Group. Dose comparison trial of sustained-release fampridine in multiple sclerosis. Neurology. 2008 Oct 7;71(15):1134-41. Kryscio RJ. Fampridine for MS responders: clinically relevant or hypothesis generating? Neurology. 2008 Oct 7;71(15):1130-1.

5. 6. 7. 8.

9.

Revision/Review Date: 5/2010 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary. APPENDIX 1: The 12-Item Multiple Sclerosis Walking Scale (MSWS-12) In the past two weeks, how much has your Not at all A little Moderately MS 1. Limited your ability to walk? 1 2 3 2. Limited your ability to run? 1 2 3 3. Limited your ability to climb up and 1 2 3 down stairs? 4. Made standing when doing things 1 2 3 difficult? 5. Limited your balance when standing or 1 2 3 walking? 6. Limited how far you are able to walk? 1 2 3 7. Increased the effort needed for you to 1 2 3 walk? 8. Made it necessary for you to use 1 2 3 support when walking indoors (e.g. holding onto furniture, using a stick, etc.)? 9. Made it necessary for you to use 1 2 3 support when walking outdoors (e.g. using a stick, a frame, etc.)? 10. Slowed down your walking? 1 2 3 11. Affected how smoothly you walk? 1 2 3 12. Made you concentrate on your 1 2 3 walking?

Quite a bit 4 4 4 4 4 4 4 4

Extremely 5 5 5 5 5 5 5 5

4

5

4 4 4

5 5 5

Adapted from: Hobart JC, Riazi A, Lamping DL, Fitzpatrick R. Measuring the impact of MS on walking ability. Neurology 2003;60:31-36. APPENDIX 2: The Timed 25-Foot Walk (T25FW) DESCRIPTION The Timed 25-Foot Walk (T25FW) is a quantitative measure of lower extremity function. The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The task is immediately administered again by having the patient walk back the same distance. Patients may use assistive devices when doing this task. In clinical trials, it is recommended that the treating neurologist select the appropriate assistive device for each patient. TIME LIMIT PER TRIAL 3 minutes (180 seconds) per trial. ADMINISTRATION Trial 1 The subject should be directed to one end of a clearly marked 25-foot course (clearly defined on the floor or on the wall) and instructed to stand just behind the starting line. Point out where the 25-foot course ends, then instruct the patient as follows: "I'd like you to walk 25 feet as quickly as possible, but safely. Do not slow down until after you've passed the finish line. Ready? Go." Begin timing when the lead foot is lifted and crosses the starting line. Stop timing when the lead foot crosses the finish line. Trial 2 After completing the first timed walk, position the patient just behind the line where s/he is now standing, repeat the same instructions, and have the patient complete the walk again. Assistive Devices In clinical trials and other serial studies, the goal is to use the same assistive device at each study visit. The treating neurologist should select an assistive device at the beginning of the study for each patient who needs one, keeping in mind that the patient may deteriorate modestly over the course of a trial. In general, patients should use their customary assistive device(s), NOT the least assistance possible to complete the test. For patients with significant gait impairment, the treating neurologist should have the patient use a rolling walker even if this is not the patient's customary device. In general, non-wheeled walkers should not be used. If a patient does use an assistive device, this should be noted on the Record Form. Completing the Record Form Record only the times for the two successfully completed trials of the Timed 25-Foot Walk. If the patient could not complete one or both of the trials of the Timed 25-Foot Walk, record this in the appropriate section of the Record Form. For example, if the patient's disease has progressed and/or physical limitations prohibit him or her from completing the trial, you should indicate "Unable to complete trial due to physical limitations", and record any specifics that you can observe (i.e., patient in a wheelchair now and unable to walk, etc.). If the patient did not complete a trial for any other reason, specify this as well (e.g., patient fell and was too fatigued to complete another trial; patient refused to complete trial). Adapted from: Fischer JS, Jak AJ, Kniker JE, Rudick RA et al. Mutiple sclerosis functional composite administration and scoring manual. National Multiple Sclerosis Society, Oct 2001. APPENDIX 3: The Modified Ashworth Scale (Bohannon & Smith, 1987) SCORE DESCRIPTION 0 No increase in muscle tone 1 Slight increase in muscle tone, manifested by a catch and release or minimal resistance at the end of the range of motion (ROM) when the affected part(s) is moved in flexion or extension 1+ Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM 2 More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved 3 Considerable increase in muscle tone, passive movement difficult 4 Affected part(s) rigid in flexion or extension Adapted from Katz RT. Spasticity. In: O'Young B, Young MA, Stiens SA. PM&R Secrets. Ed. Sara J Cuccurullo, MD. Philadelphia; Hanley & Belfus, 1997.

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA ARANESP® (darbepoetin alfa): 25 mcg/ml, 40 mcg/ml, 60 mcg/ml, 100 mcg/ml, 200 mcg/ml, 300 mcg/ml, 500 mcg/ml PA CRITERIA FOR APPROVAL: · The necessary lab work (listed below) is performed within 30 days of the date the request is submitted and is either documented on the PA form or submitted with the request -Hemoglobin -Hematocrit -Serum ferritin -Transferrin saturation (TSAT) -Serum iron -Total Iron Binding Capacity (TIBC) -Vitamin B12 level -Folate level -Erythropoietin level (for HIV related anemia) · Documentation submitted indicates the member has Chronic Kidney Disease related anemia and/or Chemotherapy related anemia, or anemia related to another specific medical condition.

If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. If all of the above conditions are met, place the member into one of the following categories based on diagnosis: Treatment of anemia of Pre-dialysis in chronic kidney disease patients: go to Section I Treatment of anemia in cancer patients undergoing chemotherapy: go to Section II Prescribed for anemia in HIV and/or Zidovudine-treated HIV disease: go to Section III Treatment of Ribavirin Induced anemia: go to Section IV Prescribed for other Medically Acceptable Indications: go to Section V

Section I: PA Criteria for Approval for anemia of Pre-dialysis chronic kidney disease Place the member into one of the following categories based on the members Aranesp® treatment history. Aranesp® treatment initial request (Part A) Reauthorization of Aranesp® (Part B)

Part A: Aranesp® treatment initial request · · · · · If the member has chronic renal failure, The member has a hemoglobin level < 10 g/dL OR if the member is new to the health plan and was receiving Aranesp® at the previous health plan the member has a documented (submitted lab result dated within 30 days of request) hemoglobin <12 g/dL Aranesp® ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) Documentation submitted indicates that the member is or will be prescribed maintenance iron therapy (>200 mg elemental iron orally daily or periodic IV supplementation), or if not receiving iron supplementation is having percentage transferrin saturation and ferritin levels checked every 2 months. If the member has low vitamin B12 levels and/or Folate levels, documentation submitted indicates that the member is or will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated. If the member is iron deficient (ferritin concentration <100 ng/mL and/or percentage transferrin saturation < 20%), the member is in the process of receiving either oral or IV iron supplementation or the treatment plan is to start iron therapy and will be having percentage transferrin saturation and ferritin levels monitored.

If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/mL and the transferrin saturation are > 20-55%) and not

vitamin B-12 deficient and not folate deficient, OR up to a 1 month temporary supply if the member is functionally iron deficient (ferritin concentration < 100 ng/mL and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient. If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Part B: Reauthorization Criteria for Aranesp® · If the member has chronic renal failure, and has been receiving therapy and their hemoglobin is <10 g/dL (submitted lab result dated within 30 days of request), AND if one of the following apply: a. Ordered dose of Aranesp® is reduced by 25% of previous dose if the member's Hgb is increasing by more than 1 g/dl in a 2 week period, b. Ordered dose of Aranesp® was increased and Hgb increase rate was < 1g/dL over the past 6 weeks AND the member has adequate iron stores c. No more than 1 dosage adjustment per 4 week intervals occurs If the member had normal vitamin B12 and Folate levels on the initial request OR had a low vitamin B12 and/or Folate level but has subsequently been placed on the appropriate supplementation then repeat vitamin B12 and Folate lab results are not needed until 1 year after the initial request. However if the patient was deficient in either vitamin B12 and/or Folate based on lab results from the initial request and are NOT receiving the appropriate supplementation then repeat vitamin B12 and Folate lab results must be submitted dated within 30 days of the request. The member's percentage transferrin saturation is greater than 20% and Ferritin is greater than 100 ng/ml and the member is receiving iron supplementation, if not receiving iron supplementation percentage transferrin saturation and Ferritin levels are being monitored every 2 months If the patient does no respond to treatment as measured by hemoglobulin levels or if RBC transfusions are still required after 8 weeks of therapy then the provider must submit a valid medical reason for continuation of therapy. Aranesp® ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section)

·

· · ·

If all of the above conditions are met, the request will be approved for up to a 3-month duration, if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/mL and the transferrin saturation are > 20-55%) and not vitamin B-12 deficient and not folate deficient, OR up to a 1 month temporary supply if the member is functionally iron deficient (ferritin concentration < 100 ng/mL and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient. If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section II: PA Criteria for Approval for anemia cancer patients on chemotherapy: Place the member into one of the following categories based on the members Aranesp® treatment history. Aranesp® treatment initial request (Part A) Reauthorization of Aranesp® (Part B)

Part A: Aranesp® treatment initial request · · · The member has a documented hemoglobin < 10g/dL OR if the member is new to the health plan and was receiving Aranesp® at the previous health plan and the member has a documented hemoglobin < 12g/dL Aranesp® ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) Documentation that the patient is currently receiving chemotherapy (along with documentation of the start and end date of the current course of chemotherapy). Treatment with Aranesp® should be discontinued at the completion of a course of chemotherapy.

If all of the above conditions are met, the request will be approved for up to a 6-month duration OR till the end of current course of chemotherapy (whichever comes first), if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested.

Part B: Reauthorization Criteria for Aranesp® · · · The member has been receiving therapy and their hemoglobin is < 12 g/dL Aranesp® ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) If the dose of Aranesp® is being increased and/or patient's hemoglobin level has decreased from the previous request then recent (within 30 days of the request) ferritin, percentage transferrin saturation, Vitamin B12 and Folate levels are to be submitted. In addition: o If the member is iron deficient (ferritin concentration <100 ng/mL and/or percentage transferrin saturation < 20%), AND in the process of receiving either oral or IV iron supplementation OR the treatment plan is to start iron therapy along with having the percentage transferrin saturation and ferritin levels monitored. o If the member has low Vitamin B12 levels and/or Folate levels, documentation submitted indicates that the member is OR will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated.

If all of the above conditions are met, and the member is not functionally iron (ferritin concentration is > 100-800 ng/mL and the transferrin saturation are > 20-55%), Vitamin B-12 and Folate deficient OR if the member is iron, vitamin B12 and/or folate deficient and receiving the proper supplementation, the request will be approved for up to a 6-month duration OR till the end of current course of chemotherapy (whichever comes first). However, up to a 1 month temporary supply will be approved if the member is functionally iron (ferritin concentration < 100 ng/mL and/or percentage transferrin saturation < 20%) and/or Vitamin B-12 or Folate deficient AND not receiving OR planning to start the proper supplementation. If the above criteria is not met, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section III: PA Criteria for Approval for Treatment of HIV and/or Zidovudine-treated HIV disease Place the patient into one of the following: - Aranesp® treatment initial request (Part A) - Reauthorization of Aranesp® (Part B) Part A: Aranesp® treatment initial request · · · · · · The member has a hemoglobin level < 11 g/dL OR if the member is new to the health plan and was receiving Aranesp® at the previous health plan the member has a documented (submitted lab result dated within 30 days of request) hemoglobin <12 g/dL. Patient has been receiving a highly reactive antiretroviral therapy (HAART) regimen for the past 35 days. Documentation, within 30 days of the request, that the patient has a erythropoietin level < 500 units/mL. If the member has low vitamin B12 levels and/or Folate levels then documentation submitted that indicates the member is or will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated. The requested dose is in accordance with the recommended dosing guidelines as outlined in the dosage and administration section for HIV patients below. If the member is iron deficient (ferritin concentration <100 ng/mL and/or percentage transferrin saturation < 20%), documentation was submitted indicating that the member is in the process of receiving either oral or IV iron supplementation (>200 mg elemental iron orally daily or periodic IV supplementation) or the treatment plan is to start iron therapy and then have the percentage transferrin saturation and ferritin levels monitored.

If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/mL and the transferrin saturation are > 20-55%) and not vitamin B-12 deficient and not folate deficient, OR a temporary supply of up to 1 month may be authorized if the member is functionally iron deficient (ferritin concentration < 100 ng/mL and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Part B: Reauthorization Criteria for Aranesp®

·

· · ·

· ·

If the member has been receiving therapy and their hemoglobin is < 11 g/dL(submitted lab result dated within 30 days of request), OR if hemoglobin (submitted lab result dated within 30 days of request) is > 11g/dL < 12 g/dL one of the following apply: a. The ordered dose of Aranesp® is reduced by 25% of previous dose if the rate of Hgb increase was > 1g/dL over a two week period OR the Hgb is increasing and approaching 12 g/dL. b. The ordered dose of Aranesp® is increased to 300 mcg every 2 weeks if the patient's Hgb improved < 1g/dL over a 4 weeks period (See Dosage and Administration section) and iron stores were adequate. c. An increase in dose does not occur more than once per month. The requested dose is in accordance with the recommended dosing guidelines as outlined in the dosage and administration section for HIV patients below. Patient is currently receiving HAART therapy. If the member had a normal vitamin B12 and Folate levels on the initial request OR had a low vitamin B12 and/or Folate level but has subsequently been placed on the appropriate supplementation then repeat vitamin B12 and Folate lab results are not needed until 1 year after the initial request. However if the patient was deficient in either vitamin B12 or Folate levels based on lab results from the initial request and is NOT receiving the appropriate supplementation then repeat vitamin B12 and Folate lab results must be submitted dated within 30 days of the request. If the member is iron deficient (ferritin concentration <100 ng/mL and/or percentage transferrin saturation < 20%), documentation was submitted indicating that the member is in the process of receiving either oral or IV iron supplementation or the treatment plan is to start iron therapy. Aranesp® ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section)

If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/mL and the transferrin saturation are > 20-55%) OR a temporary supply of up to 1 month may be authorized if the member is functionally iron deficient (ferritin concentration < 100 ng/mL and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section IV: PA Criteria for Approval for Ribavirin Induced Anemia Place the patient into one of the following: - Aranesp® treatment initial request (Part A) - Reauthorization of Aranesp (Part B) Part A: Aranesp® treatment initial request · · · · The member has a hemoglobin level < 11 g/dL OR if the member is new to the health plan and was receiving Aranesp® at the previous health plan the member has a documented (submitted lab result dated within 30 days of request) hemoglobin <12 g/dL Aranesp® ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) If the member has low vitamin B12 levels and/or Folate levels then documentation submitted that indicates the member is or will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated. If the member is iron deficient (ferritin concentration <100 ng/mL and/or percentage transferrin saturation < 20%), the member is in the process of receiving either oral or IV iron supplementation (>200 mg elemental iron orally daily or periodic IV supplementation) or the treatment plan is to start iron therapy and then have the percentage transferrin saturation and ferritin levels monitored. Patient is currently receiving ribavirin therapy and initiated therapy 20 weeks ago.

·

If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/mL and the transferrin saturation are > 20-55%) and not vitamin B-12 deficient and not folate deficient, OR a temporary supply of up to 1 month may be authorized if the member is functionally iron deficient (ferritin concentration < 100 ng/mL and/or percentage transferrin saturation < 20%) and/or

vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Part B: Reauthorization Criteria for Aranesp® · If the member has been receiving therapy and their hemoglobin is < 11 g/dL(submitted lab result dated within 30 days of request), OR if hemoglobin (submitted lab result dated within 30 days of request) is > 11g/dL < 12 g/dL one of the following apply: a. The ordered dose of Aranesp® is reduced by 25% of previous dose if the rate of Hgb increase was > 1g/dL over a two week period OR the Hgb is increasing and approaching 12 g/dL. b. The ordered dose of Aranesp® is increased to 300 mcg every 2 weeks if the patient's Hgb improved < 1g/dL over a 4 weeks period (See Dosage and Administration section) and iron stores were adequate. c. An increase in dose does not occur more than once per month. The member is currently receiving ribavirin therapy that was initiated 20 weeks ago, or if beyond week 20 of ribavirin therapy, documentation submitted indicates a dosage reduction of ribavirin to 600 mg/day after week 20 but the member still became anemic. If the member had a normal vitamin B12 and Folate levels on the initial request OR had a low vitamin B12 and/or Folate level but has subsequently been placed on the appropriate supplementation then repeat vitamin B12 and Folate lab results are not needed until 1 year after the initial request. However if the patient was deficient in either vitamin B12 or Folate levels based on lab results from the initial request and is NOT receiving the appropriate supplementation then repeat vitamin B12 and Folate lab results must be submitted dated within 30 days of the request. If the member is iron deficient (ferritin concentration <100 ng/mL and/or percentage transferrin saturation < 20%), documentation was submitted indicating that the member is in the process of receiving either oral or IV iron supplementation or the treatment plan is to start iron therapy. Aranesp® ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section)

· ·

· ·

If all of the above conditions are met, the request will be approved with a 3-month duration or up to the member completes Ribavirin therapy (24-48 weeks of treatment), if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section V: PA Criteria for Approval for Treatment of Other Medically Acceptable Indications Place the member into one of the following categories based on the members Aranesp® treatment history. Aranesp® treatment initial request (Part A) Reauthorization of Aranesp® (Part B)

Part A: Aranesp® treatment initial request · · · · · Documentation was forwarded indicating the medication (including dose) was prescribed or recommended by a hematologist or a specialist in the respective disease state associated anemia. The member has a hemoglobin level < 11 g/dL OR if the member is new to the health plan and was receiving Aranesp® at the previous health plan the member has a documented (submitted lab result dated within 30 days of request) hemoglobin <12 g/dL. The Aranesp® ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section. If the member has low vitamin B12 levels and/or Folate levels then documentation submitted that indicates the member is or will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated. If the member is iron deficient (ferritin concentration <100 ng/mL and/or percentage transferrin saturation < 20%), the member is in the process of receiving either oral or IV iron supplementation (>200 mg elemental iron orally daily or periodic IV supplementation) or the treatment plan is to start iron therapy and will be having percentage transferrin saturation and ferritin levels monitored.

If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/mL and the transferrin saturation are > 20-55%) and not vitamin B-12 deficient and not folate deficient, OR a temporary supply of up to 1 month may be authorized if the member is functionally iron deficient (ferritin concentration < 100 ng/mL and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Part B: Reauthorization Criteria for Aranesp® · If the member has been receiving therapy and their hemoglobin is < 11 g/dL (submitted lab result dated within 30 days of request), OR if hemoglobin (submitted lab result dated within 30 days of request) is > 11g/dL < 12 g/dL one of the following apply: a. The ordered dose of Aranesp® is reduced by 25% of previous dose if the rate of Hgb increase was > 1g/dL over a two week period OR the Hgb is increasing and approaching 12 g/dL. b. The ordered dose of Aranesp® is increased by 25% of the previous dose if the patient's Hgb improved < 1g/dL over a 4 weeks period (See Dosage and Administration section) and iron stores were adequate. c. An increase in dose does not occur more than once per month. If the member had a normal vitamin B12 and Folate levels on the initial request OR had a low vitamin B12 and/or Folate level but has subsequently been placed on the appropriate supplementation then repeat vitamin B12 and Folate lab results are not needed until 1 year after the initial request. However if the patient was deficient in either vitamin B12 or Folate levels based on lab results from the initial request and is NOT receiving the appropriate supplementation then repeat vitamin B12 and Folate lab results must be submitted dated within 30 days of the request. If the member is iron deficient (ferritin concentration <100 ng/mL and/or percentage transferrin saturation < 20%), documentation was submitted indicating that the member is in the process of receiving either oral or IV iron supplementation or the treatment plan is to start iron therapy and will be having percentage transferrin saturation and ferritin levels monitored. Aranesp® ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section)

·

·

·

If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/mL and the transferrin saturation are > 20-55%) OR a temporary supply of up to 1 month may be authorized if the member is functionally iron deficient (ferritin concentration < 100 ng/mL and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. FDA INDICATIONS: Aranesp is indicated for: Treatment of anemia associated with chronic renal failure, including patients on dialysis and patients not on dialysis. Treatment of anemia due to the effect of concomitantly administered chemotherapy based on studies that have shown a reduction in the need for RBC transfusions in patients with metastatic, non-myeloid malignancies. o Aranesp is not indicated for use in patients receiving hormonal agents, therapeutic biologic products, or radiotherapy unless receiving concomitant myelosuppressive chemotherapy o Aranesp is not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure due to the absence of studies that adequately characterize the impact of Aranesp on progression-free and overall survival. o Aranesp use has not been demonstrated in controlled clinical trials to improve symptoms of anemia, quality of life, fatigue, or patient well-being DOSAGE AND ADMINISTRATION: A. Pre-Dialysis CRF members: Therapeutic Guidelines in CRF Members for Aranesp®

Starting dose Reduce dose approximately 25% when If hemoglobin continue to increase despite a 25 % dosage reduction Dose should be temporarily withheld when Increase dose up to 25% of previous dose

0.75 mcg/kg/Q2week 1). Hemoglobin is increasing and approaching 12 g/dL OR 2). Hemoglobin increased by more than 1.0 g/dL in 2-week period Hold dose temporarily until hemoglobin begins to decrease, then restart at a dose 25% below the previous dose. Hemoglobin exceeds 12 g/dL and until hemoglobin falls to 11 g/dL. Therapy should be reinitiated at a dose approximately 25% below the previous dose. If hemoglobin increases by less than 1g/dL over a 4 week period AND The member is not functionally iron deficient (ferritin concentration <100 ng/mL and/or percentage transferrin saturation < 20%) nor deficient in vitamin B12 and folic acid. Functional iron deficiency and/or folic acid and/or vitamin B12 deficiency need to corrected prior to approval of any Aranesp® doses that exceed the initial starting dose (0.75 mcg/kg administered every 2 weeks) Must to be individualized to achieve and maintain the lowest Hgb level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dL. ­ Maintenance doses greater than the recommended initial starting dose (0.75 mcg/kg q2 weeks) will only be approved in members that do not have documented functional iron deficiency (ferritin concentration >100-800 ng/mL and percentage transferrin saturation>20-55%) nor deficient in vitamin B12 and folic acid. Between 10 g/dL and 12 g/dL or lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dL

Maintenance dose

Suggested target hemoglobin

B. Cancer members on chemotherapy, Anemia in HIV and/or Zidovudine-treated HIV disease, Ribavirin Induced anemia: Approvable Starting dose 200 mcg/Q2week Subcutaneous administration Reduce dose approximately 25% of previous dose when Dose should be temporarily withheld when 1). Hemoglobin is increasing and approaching 12 g/dL OR 2). Hemoglobin increased by more than 1.0 g/dL in 2-week period Hemoglobin exceeds 12 g/dL and until hemoglobin falls to 11 g/dL Therapy should be reinitiated at a dose approximately 40% below the previous dose. If hemoglobin increases by less than 1g/dL over a 6 week period AND The member is not functionally iron deficient (ferritin concentration <100 ng/mL and/or percentage transferrin saturation < 20%) nor deficient in Vitamin B12 and Folic acid. Functional iron deficiency and/or folic acid and/or Vitamin B12 deficiency need to be corrected prior to approval of any Aranesp® doses that exceed the initial starting dose Must be individualized ­ Maintenance doses greater than the recommended initial starting dose (200 mcg q2weeks) will only be approved in members that do not have documented functional iron deficiency (ferritin concentration >100-800 ng/mL and percentage transferrin saturation >20-55%) nor deficient in Vitamin B12 and Folic acid. ***Dose should be adjusted for each patient to maintain the lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dL. *** Target Hgb < 12 g/dL for cancer patients on chemotherapy and <12

Increase dose up to 300 mcg/Q2 week after initial 200 mcg q2week dosage Approvable Maximum Dose for Chemo Therapy induce Anemia: 4.5 mcg/kg/week

Maintenance dose

Suggested target Hemoglobin

g/dL for Anemia in HIV and/or Zidovudine-treated HIV disease or Ribavirin Induced anemia or lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dL. C. Other Medically Acceptable Indications Dosing Guidelines: · Based on the medical compendia (Drug Points, Micro Medex, AHFS) and standard of care clinical guidelines, the dose is appropriate for the medically acceptable indication being treated, or is equivalent to the recommended Procrit® dose as indicated below under "Conversion from epoetin alfa (Procrit®) to darbepoetin". If the member was receiving Procrit®, the ordered dose of Aranesp® is equal to the recommended dosage conversion as indicated below under "Conversion from epoetin alfa (Procrit®) to darbepoetin'. · Dosage adjustments: o Decrease dose by 25% when: Hgb increases by > 1.0 g/dL in a 2-week period Or Hemoglobin is increasing and approaching 12 g/dL o Temporarily hold dose when: Hgb exceeds 12 g/dL and until Hgb falls to below 11 g/dL Therapy can be reinitiated at a dose approximately 25% below the previous dose o Increase dose by 25%, if the member's Hgb does not increase by 1 g/dL after 4 weeks of therapy as long as the member is not iron, vitamin B12 and folate deficient · Target Hgb: <12 g/dL or lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dL D. Conversion from epoetin alfa (Procrit®) to darbepoetin: Estimate the starting weekly dose of darbepoetin based on the weekly epoetin alfa dose at the time of substitution. Titrate doses to maintain the target hemoglobin. Because of the longer serum half-life, administer darbepoetin less frequently than epoetin alfa. Administer once a week if member was receiving epoetin alfa 2 to 3 times weekly. Administer darbepoetin once every 2 weeks if the member was receiving epoetin alfa once per week. Maintain the route of administration (IV or SC). Estimated Darbepoetin Starting Doses Based on Previous Epoetin Alfa Dose Previous weekly epoetin alfa dose Every 2 weeks or weekly starting darbepoetin dose (units/week) (mcg) < 2500 25 every 2 weeks 2500 to 4999 25 every 2 weeks 5000 to 10,999 25 once weekly 11,000 to 17,999 40 once weekly 18,000 to 33,999 60 once weekly 34,000 to 89,999 100 once weekly 90,000 200 once weekly

REFERENCES: 1. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease, 2000. Am J Kidney Dis 37:S182-S238, 2001 (suppl 1) 1. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Cancer and Treatment-Related Anemia. Version 1.2008. 2. Rizzo JD, Lichtin AE, Woolf SH, Seidenfeld J, Bennett CL, Cella D, Djulbegovic B, Goode MJ, Jakubowski AA, Lee SJ, Miller CB, Rarick MU, Regan DH, Browman GP, Gordon MS. Use of Epoetin in Patients with Cancer: Evidence-Based Clinical Practice Guidelines of the American Society of Clinical Oncology and the American Society of Hematology. Journal of Clinical Oncology, Vol 20, No. 19 (October 1), 2002: pp 4083-4107. Available from URL: http://www.asco.org/asco/downloads/guidelines/2002EPO.pdf 3. Lichtin A. The ASH/ASCO clinical guidelines on the use of erythropoietin. Best Practice & Research Clinical Haematology. 2005; 18(3):433-438. 4. Suranyi M, Lindberg J, Navarro J, and Brenner R et al. Treatment of anemia with Darbepoetin Alfa Administered de novo Once Every Other Week in Chronic Kidney Disease. Am J Nephrology. 2003; 23:106-111. 5. Volberding PA, Levine AM, Dietrich D, et al. Anemia in HIV Infection: Clinical Impact and Evidence-Based Management Strategies. Clinical Infectious Diseases 2004;38:1459-68 6. HIV and AIDS Anemia and Fatigue. [resource on World Wide Web]. URL: http://www.hivandhepatitis.com/recent/lipo/071902_anemia.html#who 7. Schwartzberg L, Shiffman R, and Tomita D et al. A Multicenter Retrospective Cohort Study of Practice Patterns and Clinical Outcomes of the Use of Darbepoetin alfa and Epoetin Alfa for Chemotherapy-Induced Anemia. Clinical Therapeutics; vol.25, No.11: 2003.

8. 9. 10. 11. 12. 13.

Navarro J, roger S, and Churchill D et al. Aranesp Administered Once Every Other Week Treats Anemia in Patients with Chronic Kidney Disease Not Receiving renal Replacement Therapy. Journal of American Society of Nephrology.vol. 13, No. 9:2002 Patton, J, Wallace J. Darbepoetin alfa 200mcg Every 2 Weeks and Epoetin alfa 40,000 U Every Week in Chemotherapy Induced Anemia Patients Result in Similar Initial Hemoglobin Outcomes. ISPOR: 2003. Schwartzberg L, Yee L, and Senecal F et al. Darbepoetin 200mcg Every 2 Weeks vs Epoetin alfa 40,000 U Weekly in Anemic Patients Receiving Chemotherapy. American Society of Clinical Oncology Meeting Proceedings, Volume 23: 2004. Thames W, Smith S, and Scheifele A et al. Evaluation of the US Oncology Network's Recommended Guidelines for Therapeutic Substitution with Darbepoetin alfa 200mcg Every 2 Weeks in Both Naïve Patients and Patients Switched from Epoetin alfa. Pharmacotherapy 2004; 24(3):313-323. Agarwal A, Ling B, and Walczyk M et al. Aranesp administered once monthly maintains hemoglobin levels in patients with chronic kidney disease.2004 National Kidney Foundation Clinical Meeting: April 28-May 2, 2004.Chicago, IL. Poster# 86. Agarwal A, Ling B, and Walczyk M et al. Aranesp administered once monthly maintains hemoglobin levels in patients with chronic kidney disease. American Journal of Kidney Diseases;vol 43, No 4: April 2004. Aranesp® (darbepoetin alfa). Prescribing Information, Amgen. June 2011

14.

Review Date: 8/2011 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION PROTOCOL FOR BOTULINUM TOXINS A & B Abobotulinumtoxin A: (DysportTM): 500 units vials Onabotulinum toxin type A: (Botox®) 100 units vials Rimabotulinum toxin type B: (Myobloc®) 5,000 units/mL (in 0.5 mL, 1 mL, 2 mL single- use vials) Incobotulinum toxin A: (Xeomin®): 50 units, 100 unit vials PREFERRED PRODUCT: MYOBLOC® PREFERRED IN SELECT DISEASE STATES Initial Approval:

The request for the medication is for an Food and Drug Administration (FDA) approved indication, and/or is used for a medical condition (See Medically Accepted Uses section below) that is supported by the medical compendium (Micromedex, American Hospital Formulary Service (AHFS), United States Pharmacopeia Drug Information for the Healthcare Professional (USP DI) , Drug Package Insert) as defined in the Social Security Act 1927 and/or per Standard of Care Guidelines in each respective disease state. AND Documentation was submitted, that the patient has a (consistent with pharmacy claims data) adequate trial (including dates of treatment at maximum recommended doses of therapy) of standard conventional first line therapy for their respective disease state (where applicable) as recommended by the medical compendia and standard of care guidelines and/or has a documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not taking standard conventional first line therapy to treat their medical condition. AND If the medication request is for Botulinum toxin type A (Botox) for treating the following medical conditions: Spasmodic Torticollis (Cervical Dystonia), Severe Primary Axillary Hyperhidrosis, Spastic Dysphonia, the patient has a documented (consistent with pharmacy claims data) treatment failure after receiving an adequate trial (including dates, 3 months or more of therapy) of Botulinum toxin type B (Myobloc) and/or has a documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not utilizing Botulinum toxin type B (Myobloc) to manage their medical condition. **Note** Use of these medications for cosmetic purposes is not a covered benefit under the Medical Assistance Program. AND If the medication request is for Botulinum toxin type A (Botox) for treating Chronic Migraines, the patient has a documented (consistent with pharmacy claims data) treatment failure after receiving an adequate trial of beta blockers (e.g. metoprolol, atenolol, nadolol, propranolol, timolol), tricyclic antidepressants (e.g. amitriptyline), depakote, and topiramate. AND Prescribed dosing of medication is within FDA approved indications and/or is supported by the medical compendium as defined by the Social Security Act and/or per Standard of Care Guidelines in each respective disease state.

If all of the above conditions are met, the request will be approved for up to 3 months or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per Standard of Care Guidelines in each respective disease state; if all of the above criteria are not met, then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Reauthorization of Medication: The prescribing physician has provided documentation as to the clinical benefits of the medication supporting continued treatment, OR the medication is being continued in accordance with the recommended time as defined by FDA drug package insert, and/or per recommendations of the medical compendium as described above, and/or per Standard of Care Guidelines in each respective disease state. AND Prescribed dosing of medication is within FDA approved indications and/or supported by the medical compendium as defined by the Social Security Act and/or per Standard of Care Guidelines in each respective disease state.

If all of the above conditions are met, the request will be approved for up to 3 months or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per Standard of Care Guidelines in each respective disease state; if all of the above criteria are not met, then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Medically Accepted Uses and Dosing: Abobotulinumtoxin A: (DysportTM):

Spasmodic torticollis (cervical dystonia) - (FDA approved): 500 units given intramuscularly as a divided dose among affected muscles in patients with or without a history of prior treatment with botulinum toxin. Doses above 1000 units have not been systematically evaluated. Re-treatment, if needed, should not occur in intervals of less than 12 weeks. Botulinum toxin type B: (Myobloc®): Spasmodic torticollis (cervical dystonia) - (FDA approved): 2,500-5,000 units divided among affected muscles in patients with a prior history of tolerating botulinum toxin. Patients without a prior history of tolerating botulinum toxin should receive a lower initial dose. The duration of effect in patients who responded to treatment (of doses of 5,000 -10,000 units) in studies was between 12 and 16 weeks. Severe Primary Axillary Hyperhidrosis: - 200-250 units injected into 10 to 15 sites in each axilla. Doses as high as 2000-5000 units per axilla have been used. Response duration 2 to 8 months (avg 5 months). Excessive Salivation in Parkinson: 1000 units into each parotid gland and 250 units into each submandibular gland. Response duration of up to 20 weeks. Incontinence in Spinal Cord Injury: 5000 units into detrussor muscle sites (trigone typically exempt). Response duration of up to 1 month. Spastic Dysphonia: 500-750 units into thyroarytenoid muscles. 25-100 units to each vocal cord via the cricothyroid membrane. Response duration of up to 14 weeks. Upper Limb Spasticity from Cerebral Vascular Accidents or from Traumatic Brain Injury: 5000-17,500 total limb dose divided into specific muscles. Average of 375-2500 for arm muscles. Response duration from 4 to 12 weeks. Onabotulinum toxin type A: (Botox®) Spasmodic torticollis (cervical dystonia) (FDA approved): 100 to 300 Units (lower dose for patients without prior use of botulinum toxin to limit incidence of dysphagia) divided among affected muscles; limit total dose to 100 Units or less may decrease the incidence of dysphagia. Response duration up to 3 months. Blepharospasm (FDA approved) (Adult and Pediatric): 1.25-2.5 units into injected into the medial and lateral pre-tarsal orbicularis oculi of the upper lid and into the lateral pre-tarsal orbicularis oculi of the lower lid. The cumulative dose in a 30-day period should not exceed 200 units. Response duration up to 3 months. Repeat treatments needed prior to 3 months are considered insufficient and the dose can be increased up to two-fold up to 5 units per site. Strabismus (FDA approved): Initial doses: For vertical muscles and for horizontal strabismus of less than 20 prism diopters: 1.25 - 2.5 units in any one muscle. For horizontal strabismus of 20 prism diopters to 50 prism diopters: 2.5 - 5.0 units in any one muscle. For persistent VI nerve palsy of one month or longer duration: 1.25 - 2.5 units in the medial rectus muscle. Subsequent doses for residual or recurrent strabismus: It is recommended that patients be re-examined 7-14 days after each injection to assess the effect of that dose. Patients experiencing adequate paralysis of the target muscle that require subsequent injections should receive a dose comparable to the initial dose. Subsequent doses for patients experiencing incomplete paralysis of the target muscle may be increased up to two-fold compared to the previously administered dose. The cumulative dose in a 30-day period should not exceed 200 units. Subsequent injections should not be administered until the effects of the previous dose have dissipated as evidenced by substantial function in the injected and adjacent muscles. The maximum recommended dose, as a single injection for any one muscle, is 25 units. Severe Primary Axillary Hyperhidrosis Inadequately Managed by Topical Agents (FDA approved): The recommended dose is 50 units per axilla. Retreatment when clinical effect diminished. Chronic Migraine (FDA Approved): For prophylaxis of headaches in adult patients with chronic migraine (15 days per month with headache lasting 4 hours a day or longer). 155 Units administered intramuscularly (IM) as 5 units/0.1 mL per each site. Injections should be divided across 7 specific head/neck muscle areas: frontalis, corrugator, procerus, occipitalis, temporalis, trapezius, cervical paraspinal muscle group. All muscles should be injected bilaterally with half the number of injection sites administered to the left, and half to the right side of the head and neck. Retreatment should occur every 12 weeks. Bladder Muscle Dysfunction (overactive, neurogenic) (FDA approved): 200, as 1 ml injections across 30 sites into the detrusor.

Excessive Salivation in Parkinson, Multiple System Atrophy, Neulogical Disorders, Bulbar Amyotrophic Lateral Sclerosis (Adult and Pediatric): 5-30 units injected in divided doses into the parotid and submandibular glands at doses calculated by patient weight and rate of salivation. Response duration from 1 to 3 months. Incontinence in Spinal Cord Injury or Trauma: 80-100 units given as a single injection or monthly for 2-3 months. Single injection method response duration is about 2-3 months; monthly injection method response duration is 9-13 months. Spastic Dysphonia: Average dose of 10 units per side with higher doses up to 20 units required for abductor and adductor laryngeal involvement. Response duration up to 6 months. Upper Limb Spasticity from Cerebral Vascular Accident: 75-300 units divided among affected muscles. Response duration about 12 weeks. Upper Limb Spasticity from Traumatic Brain Injury: Dose depends on muscle injected. Doses range from 20 to 300 units injected in divided doses to affected muscles. Response duration about 4-6 months. Lower Limb Spasticity from Cerebral Vascular Accident or Traumatic Brain Injury: 20-500 units injected in divided doses to affected muscle group. Response duration 8-12 weeks. Lower limb spasticity has inconclusive evidence on efficacy. Abducens Nerve Palsy: 2.5 ­5 units injected into the medial rectus muscles. Response duration from 3-6 months. Achalasia: 80-100 units injected into the lower esophageal sphincter. Response duration 1 year. Auriculotemporal Syndrome (Frey's Syndrome): 1-2 units per 2.25 cm2 of hyperhidrotic skin as visualized by the iodine starch test. Total dose 21-65 units. 1-3 sessions necessary. Response duration from 6-12 months. Fibromyalgia: 80-200 units injected into affected muscles. Response duration up to 2 months. Hemifacial spasm: 15-30 units divided among affected muscles. Response duration from 3 to 5 months. Lower limb Spasticity in Multiple Sclerosis: 155-400 units divided among affected muscles per session. Response duration 1-3 months. Cerebral Palsy (CP): For lower-limb spacticity in pediatric CP: candidates for treatment with botulinum toxin include those with dynamic equines persistent throughout the gait cycle, equinovarus deformity, a dynamic knee flexion angle exceeding 20 degrees during the gait cycle or one that interferes with gait, or substantial scissoring and adduction at the hips. For upper-limb spacticity in adult (up to 21 y/o) and pediatric CP: candidates for treatment with botulinum toxin include those with persistent thumb in palm or thumb adduction, wrist posture that prevents effective use, or tight elbow flexion. Dose: 1-8 units/kg divided among affected muscles. Response duration typically 1 to 3 months. Myofascial Pain Syndrome: 50-150 units depending upon the injected muscle. Response duration is based on relief of pain. Documentation must be submitted that the patient failed first line therapy consisting of injections of local anesthetics and corticosteroids to trigger points as well as massage and physical therapy, and lifestyle changes to reduce stress. Oromandibular Dystonia: For jaw-closing type use 25-50 units into each masseter muscle. If satisfactory results are not obtained, 540 units may be injected into each temporalis muscle. Response duration 2-4 months. Incobotulinum toxin A: (Xeomin®): Spasmodic torticollis (cervical dystonia) (Adult) - (FDA approved): The recommended total dose is 120 Units per treatment session. Higher doses did not provide additional efficacy and were associated with an increased incidence of adverse reactions. Blepharospasm (FDA approved) (Adult): In patients who have been previously treated with onabotulinumtoxin A (Botox). When initiating treatment, the dose, number, and location of injections should be based on the previous dosing of onabotulinumtoxin A (Botox). If the previous dose of onabotulinumtoxin A (Botox) is not known, the recommended starting dose is 1.25 ­ 2.5 Units per injection site. In clinical trials, the mean dose per injection site was 5.6 Units, the mean number of injections per eye was 6, and the mean dose per eye was 33.5 Units. **Note** Use of these medications for cosmetic purposes is not a covered benefit under the Medical Assistance Program. References:

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21.

22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33.

34.

35. 36. 37. 38. 39. 40. 41. 42.

Factor S. Adler C. Brashear A. et al. Practical considerations for the clinical use of botulinum toxin type B. A self-study continuing medical education activity. We Move. Worldwide Education and Awareness for Movement Disorders. Release date 2/02. Blitzer A. Botulinum Toxin A and B: A comparative dosing study for spasmodic dysphonia. Otolaryngology 2005; 133:836-838. Costa J. Borges A. Espirito-Santo C. Ferreira J. Coelho M. Moore P. Sampaio C. Botulinum toxin A versus botulinum toxin type B for cervical dystonia. The Cochrane Library 2006; Volume (2). Thakker M. Rubin P. Pharmacology and clinical applications of botulinum toxins A and B. International Ophthalmology Clinics; Issue 3: Vol (44): p147-163. Barnes M. Botulinum toxin-mechanisms of action and clinical use in spasticity. J Rehabil Med 2003; Suppl. 41: 56-59. Cheng. Christine M. Chen. Jennifer S. Patel. Rosalie P. Unlabeled uses of botulinum toxins: A review, part 2. AM J Health, Vol 63(3). Feb 1,2006.225-232. Cheng. Christine M. Jennifer S. Chen. Rosalie P. Patel. Unlabeled uses of botulinium toxins: A review, part 1. AM J Health, Vol 63(3). Jan 15,2006.145-152. Bhidayasiri R. Truong D. Expanding use of botulinium toxin. Journal of the Neurological Sciences 2005; 235:1-9. Boyd R. Hays R. Current evidence for the use of botulinum toxin type A in the management of children with cerebral palsy: a systemic review. European Journal of Neurology 2001;8(Supply5): 1-20. Dodick D. Blumenfeld A. Silberstein S. Botulinum neurotoxin for the treatment of migraine and other primary headache disorders. Clinical in Dermatology 2004; 22:76-81. Watts C. Nye C. Whurr R. Botulinum toxin for treating spasmodic dysphonia(laryngeal dystonia): a systemic Cochrane review. Clinical Rehabilitation 2006; 20:112-122. Gage J. Novacheck T. An update on the treatment of gait problems in cerebral palsy. Journal of Pediatric Orthopaedics 2001; 10:265-274. Dutton J. White J. Richard M. Myobloc for the treatment of benign essential blepharospasm in the patients refractory to botox. Opthalmic Plastic and Reconstructive Surgery 2006; Vol.22, No. 3, pp 173-177. Berman B, Seeverger L, Kumar R. Long term safety and efficacy, dosing and development of resistance with botulinum toxin type B in cervical dystonia. Mov Disorders 2005; 20(2): 233-7 Brashear A, Lew MF, Dykstra DD, et al.: Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia. Neurology 1999 October 22;53(7):1439-45. Brin MF, Lew MF, Adler CH, et al.: Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia. Neurology 1999 October 22;53(7): 1431-8. Comella CL, Jankovic J.: Comparison of botulinum toxin serotype A and B for the treatment of cervical dystonia. Neurology 2005 November 65(9): 1423-29. Factor SA, Molho ES, Evans S, Reustel PJ. Efficacy and safety of repeated doses of botulinum type B in type A resistant and responsive cervical dystonia. Mov disorders 2005; 20(9): 1152-60. Fahn S edited by Jankovic J. Chapter 8 Dystonia. Therapy with Botulinum Toxin Textbook. Lew MF. Botulinum toxin type B. An effective treatment for alleviating pain associated with cervical dystonia. Journal of Back and Musculoskeletal Rehabilitation 2002; 16:3-9. Leong M, Royal M. A randomized double-blind study to compare the efficacy and safety of Neurobloc (MYOBLOC) botulinum toxin type-B with Botox (botulinum toxin type-A) in toxin-naïve subjects with cervical dystonia. Poster presentation at International Conference 2005 Basic and therapeutic aspects of botulinum and tetanus toxins, Denver, CO, June 23-25, 2005 (under auspices of the Neurotoxicity Society). Sunter W, Leong M, Royal M. The cervical dystonia subset of the mind registry database. Poster Presentation international conference 2005 basic therapeutic aspects of botulinum and tetanus toxins, Denver, CO, June 23-25, 2005 (under auspices of the Neurotoxicity Society). Bell K, Williams F. Use of Botulinum Toxin type A and type B for spasticity in upper a lower limbs. Phys ed rehabil Clin N Am. (2003) 14: 821-35. Brashear A, McAfee AL, Kuhn ER, Ambrosius WT. Treatment with botulinum toxin type B for upper-limb spasticity. Arch Phys Med Rehabil 2003:84(1): 103=07. Brashear A, McAfee AL, Kuhn ER, Fyffe J. Botulinum toxin type B in upper-limb poststroke spasticity: a double-bind placebo controlled trial. Arch Phys Med Rehabil 2004;85(5): 705-09. Brinke M. Combined treatment of spastic dysbalance of the hand with botulinum toxin type B followed by constrained-induced movement therapy. J Neurol Rehabil 2002;8(6):311-14. Fried GW, Fried KM. Spinal cord injury and use of botulinum toxin in reducing spasticity. Phys Med Rehabil Clin N Am. (2003) 14:901-10. McGuire J. Effective use of chemodenervation and chemical neurolysis on the management of poststroke spasticity. Topics in Stroke Rehab 2001; 8(1): 47-55. O'Brien CF. Treatment of spasticity with botulinum toxin. Clin J Pain 2002;Dec 18 (supp6): 182-90. Oechsner M. Treatment of hip adductor spasticity with botulinum toxin type B. Nervenarzt 2002;73(12): 1179-82 Fried Gw. Botulinum toxin type B improves spasticity and function in patients with quadriplegia. Archives of Pharmacology 2002; June 365 (supp2): R20 poster presented at toxins, June 8-11, 2002. Fried GW. Botulinum toxin type B improves pain and function in patients with spasticity due to quadriplegia. Archive of Pharmacology 2002; June 2002 (supp20): R42 poster presented at toxins, June 8-11, 2002. Hecht JS, Preston L, Harriman, MCPhee S. Effects of botulinum toxin type B on shoulder pain, hypertoina, and functioning adults with spastic hemiparesis. Arch Phys Med and Rehabil 2002; Nov. 83(11). Poster presented at 63rd Annual Assembly of the American Academy of Physical Medicine and Rehabilitation. Nov. 21-24, 2002. Jayasooriya S, Francisco GE, Healy W. Early experience with the use of MYOBLOC (botulinum toxin type B) for the treatment of upper limb spasticity hypertonia. Arch Phys Med Rehab 2002; Nov. 83(11); 1677. Poster presented at 63rd Annual Assembly of the American Academy of Physical Medicine and Rehabilitation, Nov. 21-24, 2002. Smith H, Dubin A, Tang J. Evaluation of botulinum toxin type B for a patient with painful muscle spasms. Archives of pharmacology2002; June 365 (supp2): R42. Poster presented at toxins June 8-11, 2002; and 21st Annual Scientific Meeting of the American Pain Society. March 14-17, 2002. Adler CH, Bansberg SF, Krein-Jones, Hentz JG. Safety and efficacy of botulinum toxin type B (MYOBLOC) in adductor spasmodic dysphonia. Movement Disorders 2004; Vol. 3, Issue 9: 1075-79. Gutinas-Lichius O. Injection of botulinum toxin type B for the treatment of otolaryngology patients with secondary treatment failure of botulinum toxin type A. Laryngoscope 2003 April; 113(4): 743-45. Baumann L, Slezinger A, Halem M, et al. Pilot study on the safety and efficacy of MYOBLOC (botulinum toxin type B) for the treatment of axillary hyperhidrosis. Int J Dermatol 2005 May; 44(5): 418-24. Baymann L, Slezinger, Halem M, et al. Double-blind, randomized, placebo-controlled pilot study of the safety and efficacy of MYOBLOC (botulinum toxin type B) for the treatment of palmar hyperhidrosis. Dermatol Surg 2005 March; 31(3): 263-70. Baumann L, Halem M. Botulinum toxin-B and the management of hyperhidrosis. Clinics and Dermatology 2004; 22: 60-65. Dressler D, Saberi FA, Benecke R. Botulinum toxin type B for the treatment of axillar hyperhidrosis. J Neurol. 2002; 249: 1729-32. Hecht MJ, Birklein F, Winterholler M. Successful treatment of axillary hyperhidrosis with very low doses of botulinum toxin B: A pilot study. Arch Dermatol Res 2004 February; 295(8-9): 318-19.

43. Winterholler M, Eisenbarth G, Erbguth, Briklein F. A systematic analysis of dose related local antihydrotic effects of NeuroBloc/MYOBLOC (botulinum toxin type-B) injected as measured sudometry, Movement Disorders 2002; 17(supp5): S41. Poster presentation toxins June 8-11, 2002. 44. Colosimo C, Chianese M, Giovannelli M, Contarino MF, Bentivogilo AR. Botulinum toxin type B in blepharospasm and hemifacial spasm (Letter) J Neurol Neurosurg Psychiatry 2003; 74: 687. 45. Samanta JE, Stacy MA. Efficacy of botulinum toxin type-B (MYOBLOC) in case of hemifacial spasm. Movement Disorders 2002; 17(supp): S286. Poster presentation at toxins, Hanover, Germany June 8-11, 2002. 46. Arezzo J. Possible mechanisms for the effect of botulinum toxin on pain. Clinic J of Pain; Vol 18, No. 6 Supplemental 2002; S125-S131. 47. Argoff CE. A focused review of the use of botulinum toxins for neuropathic pain. The Clinical J of Pain 2002; 18; S177 48. Fishman LM, Konnoth C, Rozner B. Botulinum neurotoxin type-B and physical therapy in the treatment of piriformis syndrome: A dose finding study. Am J Med Rehabilitation 2003; 83: 42-50. 49. Fadeyi MO. Adams QM. Uses of botulinum toxin type-B for migraine and tension type headaches. American Journal of Health System Pharmacists. 2002;13(3):79-85. 50. Loder E. Biondi D. Use of botulinum toxin for chronic headache: A focused review: Clinical Journal of Pain. 2002;18(supp 6):S169-S176. 51. Gooch JL. Patton CP. Combining botulinum toxin with phenol to manage spasticity in children. Archives of Physical Medicine and Rehabilitation. 2004;85(7):1121-1124. 52. Turk-Gonzales M. Odderson IR. Quantitative reduction of saliva production with botulinum toxin type-B injections into the salivary glands. Neurorehabilitation Neural Repair. 2005:19(1):58-61. 53. Critchfield J. Considering the immune response of botulinum toxin. Clinical Journal of Pain. 2002;18:S133-S141. 54. Schwartz M. Freund B. Treatment of temporomandibular disorders with botulinum toxin. Clinical Journal of Pain. 2002;Vol18 No 6 (supp): S198-S203. 55. Silberstein SD. Practice parameter: Evidence-based guidelines for migraine headache (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000;55;754. 56. Aurora SK, Dodick DW, Turkel CC, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia. 2010 Jul;30(7):793-803. 57. Diener HC, Dodick DW, Aurora SK, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia. 2010 Jul;30(7):804-14. 58. Package Labeling Botox®, Allergan Pharmaceuticals Ireland. 11/2011. 59. Package labeling. Myobloc® Solstice Neurosciences, Inc. San Francisco, CA 94080. 05/2010. 60. Package labeling. DysportTM. Ispen Biopharm Ltd. Brisbane, CA. 4/2010. 61. Package labeling. Xeomin®. Merz Pharmacueticals, LLC. Greensboro, NC 27410, 7/2011 Revision/Review Date: 05/2012 Associated Policy: Prior Authorization of Medications 236.200

NOTE: Clinical reviewer must override criteria when, in his/her professional judgement, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA

CINRYZETM (C1 Inhibitor (human)): Injection: 500 Units/vial PA CRITERIA FOR INITIAL AUTHORIZATION: · Documentation that the patient has clinical findings of hereditary angioedema (HAE) which include documented family history, onset of symptoms in childhood or young adulthood, recurrent angioedema without urticaria, and/or attacks that do not respond to treatment with antihistamines or corticosteroids. In addition, laboratory finding of HAE which include serum complement factor 4 (C4) level and the function of the C1-inhibitors are decreased and the level of antigenic C1-inhibitors are decreased or normal. AND · Documentation that the patient has experienced severe HAE (that patients has a history of 1 severe event per month, is disable more than 5 days per month, or has a history of airway compromise during a previous attack). AND · Documentation of a trial and failure or intolerance with Danazol®. If the above conditions are met, the request will be approved for a duration of 4 month; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR AUTHORIZATION FOR USE IN A NON-FDA APPROVED MEDICALLY ACCEPTED INDICATION: · · · The medication is recommended and prescribed by a specialist in the field to treat the member's respective medical condition. The medication is prescribed for a non-FDA approved indication but is considered to be a medically accepted use of the medication per the medical compendia (i.e. Micromedex, Drug Points, and AHFS drug information) as defined by the Social Security Act and/or the standard of care guidelines. Documentation was submitted indicating that the member has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates, doses of medications) of all first line medical therapies as recommended by the medical compendia and standard care guidelines and/or has another documented medical reason (intolerance, contraindications, etc.) for not receiving or trying all first line medical treatment(s). The medication is prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, Drug Points, and AHFS drug information) as defined by the Social Security Act and/or per the standard of care guidelines.

·

If the above conditions are met, the request will be approved for a duration of 4 month; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR RE-AUTHORIZATION FOR USE IN A NON-FDA APPROVED MEDICALLY ACCEPTED INDICATION: · The medication is recommended and prescribed by a specialist in the field to treat the member's respective medical condition. · The medication is being prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, Drug Points, and AHFS drug information) as defined by the Social Security Act and/or per the standard of care guidelines. · Documentation from medical charts indicating continuation of therapy due to the member significantly clinically benefited from the medication If the above conditions are met, the request will be approved for a duration of 4 month; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. FDA APPROVED INDICATIONS

Cinryze® is a C1 inhibitor indicated for routine prophylaxis against angioedema attacks in adolescent and adult patients with Hereditary Angioedema (HAE). DOSAGE AND ADMINISTRATION:

Routine prophylaxis against HAE attacks:

· A dose of 1,000 units of Cinryze can be administered every 3 or 4 days for routine prophylaxis against angioedema attacks in HAE patients. · Cinryze is administered at an injection rate of 1 ml per minute. Indication Total Dose Initial Infusion Rate Maintenance Infusion Rate (if tolerated) Routine prophylaxis 1,000 units IV every 3 1 ml/min (10 minutes) 1 ml/min (10 minutes) against HAE attacks or 4 days

REFERENCES: 1. Cinryze Prescribing Information, Lev Pharmaceutical Inc, 10/2008. 2. Bowen T, Cicardi M, Bork K, et al. Hereditary Angiodema: a current state-of-the-art review, VII: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Ann Allergy Asthma Immunol. 2008; 100(supl 2);S30-S40. 3. Bruce L Zuram. Hereditary Angioedema. N Engl J Med 2008;359:1027-36. 4. Timothy J Craig. Appraisal of danazol prophylaxis for hereditary angioedema. Allergy Asthma Proc 2008;29:225-31 5. Bork K, Bygum A, Hardt J. Benefits and risks of danazol in hereditary angioedema: a long-term survey of 118 patients. Ann Allergy Asthma Immunol. 2008;100:153-61 Revision/Review Date: 2/2009 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA EPOGEN® (epoetin alfa): 2,000 units/ml, 4,000 units/ml, 10,000 units/ml, 3,000 units/ml, 20,000 units/ml, 40,000 units/ml ® OMONTYS (peginesatide): single-use vials: 2mg, 3mg, 4mg, 5mg, 6mg single use pre-filled syringes: 1mg, 2mg, 3mg, 4mg, 5mg, 6mg multiple use vials: 10mg/ml and 20mg/2ml PA Criteria for Approval of Administration of Epogen in ESRD Patients Treated at Dialysis Centers). ESRD: End Stage Renal Disease Patient is being treated at a dialysis center. AND The necessary lab work (listed below) is documented on the PA form or submitted with request; -Hemoglobin ­ last 3 months results (to determine rolling Hgb) -Hematocrit ­ last 3 months results (to determine rolling Hct) -Reticulocytes ­ within past 2 months. -Serum ferritin ­ within past 2 months -Transferrin saturation ­ within past 2 months -Serum iron ­ within past 2 months. -Total Iron Binding Capacity (TIBC) ­ within past 2 months -Red cell indices (MCV, MCHC, RDW etc.) ­ within past month -Vitamin B12 and Folate levels ­ within past 2 months -History of Epogen usage If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. If all of the above conditions are met, place the patient into one of the following categories based on diagnosis: Place the patient into one of the following categories -Epogen treatment naïve with normal iron status (Section A) -Epogen treatment naïve with iron deficiency (Section B) -Receiving Epogen treatment with normal iron status (Section C) -Receiving Epogen treatment with iron deficiency (Section D) Section A: Epogen treatment naïve with normal iron status (TSAT > 20% and Ferritin > 100ng/ml) The patient has a hemoglobin <11g/dL and/or hematocrit <33%. Epogen dosing is being initiated at100 units/kg- 3 times a week (TIW) or less. The patient is receiving maintenance iron therapy (25-125 mg IV once weekly or >200 mg elemental iron orally daily). If the medication request is for Omontys or any other newly marketed erythropoiesis-stimulating agent (ESA), the patient has a documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not taking Epogen to treat their medical condition.

If all of the above conditions are met, the request will be approved with a 3-month duration, if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section B: Epogen treatment naïve with iron deficiency (TSAT < 20% and Ferritin < 100ng/ml) The patient has a hemoglobin <11g/dL and/or hematocrit <33%. The patient is in the process of receiving parental iron supplementation (100 mg IV every hemodialysis for 10 doses or 125 mg IV for 8 doses, maybe repeated if TSAT is less 20% and/or serum ferritin is less than 100 ng/ml, when TSAT >20% and Ferritin > 100 ng/ml then 50-100mg IV every week for 10 doses is recommended). The patient's Epogen dose is less than or equal to 100 units/kg- 3 times a week (TIW). If the medication request is for Omontys or any other newly marketed erythropoiesis-stimulating agent (ESA), the patient has a documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not taking Epogen to treat their medical condition.

If all of the above conditions are met, the request will be approved with a 2-month duration to allow follow up on outcome of iron supplementation; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section C: Existing therapy with Epogen with normal iron status (TSAT > 20% and Ferritin > 100ng/ml) The patient has a hemoglobin <12g/dL and/or hematocrit <36% The patient's hematocrit increased greater than 8 percentage points in the past month, or Hgb increased by more than 1g/dl in a two week period, after starting current dose and the Epogen dose has been reduced by at least 25% compared to the last course of therapy and therapy withheld for 1-2 weeks. If the patient's Hgb/Hct is below target range after receiving therapy for at least 4 weeks and the dose is the same as last month or was increased by no more than 25% of the previous dose. If the patient's current Epogen dose was started less than 8 week ago and their hematocrit has increased by less than 4 percentage points over the past 2 weeks or less than 8 percentage points over the last 4 weeks and the ordered dose of Epogen® is the same as last month or less. If the patient's Hgb/Hct is in target range (Hct. 33-36 and Hgb. 11-12) and the ordered dose is either reduced or the same dose as the previous month. The ordered dose is not an increase in dosage that is within 4 weeks of last dosage change or start of therapy with a medical reason being provided for an early increase. If the patient's hematocrit exceeds 36% or Hgb exceeds 12 gm/dl despite dose reduction, the Epogen dose was withheld until hematocrit dropped to 36% or less and the ordered Epogen dose was reduced by 25%. The patient is receiving maintenance iron therapy (25-125 mg IV once weekly or >200 mg elemental iron orally daily). If the dose is greater than 300 units/kg TIW, then documentation (within the past 2 months) was provided that maximum iron supplementation was attempted (despite TSAT > 20% and ferritin >100 ng/ml, the patient received 2 courses of iron supplementation at 50-100 mg per week x 10 doses to observe H/H response. After 2nd course, if no increase in H/H, but TSAT or ferritin increases, then weekly iron dose should be reduced to maintain TSAT > 20% and serum ferritin >100 ng/ml. If H/H did increase after 2nd course of iron, or remained stable after reduced Epogen dose, then a 3rd course of iron 100 mg/week x 10 dose is reasonable to achieve and maintain target H/H). Along with documentation of iron dosing, documentation (within the past 2 months) was submitted from a hematologist recommending the current dose if all reversible causes for Epogen resistance have been ruled out. If all of the above conditions are met, the request will be approved with a 3-month duration, if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section D: Existing therapy on Epogen with iron deficiency (TSAT < 20% and Ferritin < 100ng/ml) The patient has a hemoglobin <12g/dL and/or hematocrit <36% The patient is currently in the process of receiving iron supplementation (Ex:100 mg IV every hemodialysis for 10 doses, which may be repeated if TSAT is less 20% and/or serum ferritin is less than 100 ng/ml, when TSAT >20% and ferritin > 100 ng/ml then 50-100mg IV every week for 10 doses is recommended followed by maintenance dosing 25-125 mg/week) The ordered dose is an increase in dosage that is within one-month time of last dosage change or start of therapy, and a medical reason was provided for an early increase. The Epogen dose is less than or equal to 100 units/kg TIW. If all of the above conditions are met, the request will be approved with a 2-month duration to allow follow up on outcome of iron supplementation; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. FDA INDICATION: Epogen: Treatment of anemia of chronic renal failure patients Treatment of anemia in Zidovudine-treated HIV-infected patients Treatment of anemia due to the effect of concomitantly administered chemotherapy based on studies that have shown reduction in the need for RBC transfusion I patients with metastatic, non-myeloid malignancies receiving chemotherapy for a minimum of 2 months. o Epogen is not indicated for use in patients receiving hormonal agents, therapeutic biologic products, or radiotherapy unless receiving concomitant myelosuppressive chemotherapy.

Epogen is not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure due to the absence of studies that adequately characterize the impact of Epogen on progression-free and overall survival. o Epogen is not indicated for the treatment of anemia in cancer patients due to other factors such as iron or folate deficiencies, hemolysis, or gastrointestinal bleeding. o Procrit use has been demonstrated in controlled clinical trials to improve symptoms of anemia, quality of life, fatigue, or patient well-being Treatment of anemic patients (Hgb>10 to <13 g/dl) who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery to reduce the need for allogenic blood transfusion o

Omontys: Treatment of anemia of chronic kidney disease (CKD) in adult patients on dialysis Omontys is not indicated and is not recommended for use: o In patients with CKD not on dialysis o In patients receiving treatment for cancer and whose anemia is not due to CKD o As a substitute for RBC transfusions in patients who require immediate correction of anemia o Omontys has not been shown to improve symptoms, physical functioning or health-related quality of life

DOSAGE AND ADMINISTRATION: CRF patients: General Therapeutic Guidelines in CRF Patients for Epoetin Alfa Starting dose Adults: 50 to 100 Units/kg TIW Pediatric: 50 Units/kg TIW

Maximum dose ­ (with normal Iron stores) Intravenous administration

300 units/kg TIW

**Doses greater than maximum doses require hematologist consultation and recommendation. Reduce dose by 25% when

Dose should be temporarily withheld when

Increase dose up to 25% of previous dose if:

Maintenance dose

Suggested target hematocrit and hemoglobin

1) Hgb is increasing and approaching 12 g/dl and the rate of OR 2) Hgb increases by more than 1 g/dl in 2-week period Hgb exceeds 12 g/dl and until Hgb falls to 11g/dl. Therapy should be reinitiated at a dose approximately 25% below the previous dose. 1) Hgb is < 10 g/dl and has not increased by 1 g/dl after 4 weeks of therapy OR 2) Hgb decreases below 10 g/dl Individualize to achieve and maintain the lowest Hgb level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dl. 33% to 36% or 11 to 12 gm/dl

Dose adjustment should not be made more frequently than once a month, unless clinically indicated. After any dose adjustment, determine the hematocrit twice weekly for at least 2 to 6 weeks. If the hematocrit is increasing and approaching 36%, reduce the dose to maintain the suggested target hematocrit range. If the reduced dose does not stop the rise in hematocrit and it exceeds 36%, temporarily withhold doses until the hematocrit begins to decrease, then reinitiate at a lower dose. At any time, if the hematocrit increases by > 4 points in a 2-week period, immediately decrease the dose. After the dose reduction, monitor the hematocrit twice weekly for 2 to 6 weeks and make further dose adjustments as outlined in the maintenance dose section.

If a hematocrit increase of 5 to 6 points is not achieved after an 8-week period and iron stores are adequate (see Delayed or diminished response), the dose may be incrementally increased. Further increases may be made at 4- to 6week intervals until the desired response is attained.

Omontys: Initiate Omontys treatment when the hemoglobin level is less than 10 g/dl The recommended starting dose for the treatment of anemia in patients who are not currently treated with an ESA is 0.04 mg/kg body weight administered as a single intravenous or subcutaneous injection once monthly.

Estimated Omontys Starting Doses for Patients Based on Previous Weekly ESA Dose Previous Total Weekly Epoetin Alfa Dose (U/week) Less than 2,500 2,500 to less than 4,300 4,300 to less than 6,500 6,500 to less than 8,900 8,900 to less than 13,000 13,000 to less than 19,000 19,000 to less than 33,000 33,000 to less than 68,000 greater than or equal to 68,000 Previous Weekly Darbepoetin Alfa Dose (mcg/week) Less than 12 12 to less than 18 18 to less than 25 25 to less than 35 35 to less than 45 45 to less than 60 60 to less than 95 95 to less than 175 greater than or equal to 175 OMONTYS Dose Once Monthly (mg/month) 2 3 4 5 6 8 10 15 20

REFERENCES: 1. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease, September 2007. Am J Kidney Dis Vol 50 (3): pgs. 462-530. 2. Coyne DW, Kapoain T, Suki W, et al. Ferric Gluconate is Highly Efficacious in Anemic Hemodialysis Patients with High Serum Ferritin and Low Transferrin Saturaion: Results of the Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) Study. American Society of Nephrology 2007: 18; 975-84. 3. Amgen Inc. Epogen® (Epoetin Alfa). Prescribing Information, April 2009. 4. Takeda Pharmaceuticals. Omontys ® (peginesatide ). Prescribing Information, March 2012 Revision/Review Date: 05/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgement, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA FUZEON® (Enfuvirtide): 90mg vial

FOR ADULTS:

PA CRITERIA FOR INITIAL APPROVAL: · The patient has documented treatment failure to at least one sensitivity-assisted antiretroviral therapy regimen and at least two drug regimens that included two different NRTIs and two or more PIs (see table 1), or the patient has a documented medical reason for not trying two drug regimens that included two different NRTIs and two or more PIs. Refer to Fuzeon® Medication History Form and any other documentation sent by prescriber. Failure may be defined as: 1. Less than a one-log drop in viral load after 12 weeks therapy on a regimen 2. Repeated viral detection in plasma after initial suppression 3. A viral load of > 400 copies/mL after 24 weeks of continued treatment OR > 50 copies/mL after 48 weeks of continued treatment. 4. A decrease in CD4 count to less than baseline. 5. A failure to increase CD4 count by 25 ­ 50 cells/mm3 above the baseline count over the first year of therapy. 6. Clinical deterioration: defined as new AIDS-defining illness concurrent with a virological response (greater than a one-log drop) on current regimen · Recent (within 30 days or while patient was on current medication regimen) genotype and phenotype testing result was submitted with request for Fuzeon® to determine optimal regimen of at least two sensitive and tolerated anti-retroviral medications and to eliminate previously ineffective anti-retroviral medications, or there are less than two effective medications based on sensitivity testing and the patient is at risk for opportunistic infection or death. · The patient has a documented adherence level on taking anti-retroviral therapy of greater than 80% and any issue that may have caused a decrease in adherence in the past (i.e. drug or alcohol abuse, difficulty of dosing schedule, etc.) has been addressed. · Documentation of pretreatment CD4 count and viral RNA was submitted with request. If all of the above conditions are met, the request will be approved with a 16-week duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR RE-APPROVAL: · Documentation of current background drug therapy was submitted with request (Fuzeon® is not recommended as monotherapy or to be used without optimal oral therapy). · For the initial reauthorization: documentation submitted of a viral load drop of at least a one-log decrease from baseline after 12 weeks of starting therapy for requests to continue therapy beyond 16 weeks, or there is documentation provided that the patient has documented clinical improvement (i.e. increased CD4 count) with treatment. · After the initial reauthorization: documentation submitted of current (within the past 30 days) CD4 count and HIV RNA viral load. · If the patient has been on Fuzeon® therapy AND there is an increase of at least 2 log in viral load and/or a 30% decline in CD4 counts from baseline then current phenotype/genotype testing (within the past 30 days) must be submitted to indicate continued susceptibility of the HIV virus to Fuzeon®. If all of the above conditions are met, the request will be approved for up to a 6 month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested.

FOR CHILDREN:

PA CRITERIA FOR INITIAL APPROVAL: · Documentation that the patient is pre-pubertal. · The patient has documented treatment failure to at least two drug regimens that included two different NRTIs and two or more PIs (see table 1), or the patient has a documented medical reason for not trying two drug regimens that included two different NRTIs and two or more PIs. Refer to Fuzeon® Medication History Form and any other documentation sent by prescriber. Failure may be defined as: 1. For previously naïve patients or those with limited antiretroviral experience: Less than a one-log drop in viral load after 8-12 weeks therapy on a regimen. 2. For patients with more extensive antiretroviral experience: Less than a one-log drop in viral load after 6 months of continued treatment. 3. Repeated viral detection in plasma after initial suppression

·

·

4. A failure to increase CD4 count by 5% above the baseline or, for children over age of 4 -6 years old, to increase their CD4 cell count by at least 50 cells/mm3 above baseline over the first year of therapy. 5. Clinical deterioration: defined as progressive neurodevelopemental deterioration (i.e. the presence of two or more of the following findings documented on repeated assessments: impairment in brain growth, decline of cognitive function documented by psychometric testing, or clinical motor dysfunction), growth failure (i.e. persistent decline in weight-growth velocity despite adequate nutritional support and without other explanation), or severe or recurrent infection or illness (i.e. recurrence or persistence of AIDS-defining conditions or other serious infections). Recent (within 30 days or request or while patient was on current medication regimen) genotype and phenotype testing result was submitted with request for Fuzeon® to determine optimal regimen of at least two sensitive and tolerated antiretroviral medications and to eliminate previously ineffective anti-retroviral medications, or there are less than two effective medications based on sensitivity testing and the patient is at risk for opportunistic infection or death. The patient has a documented adherence level on taking anti-retroviral therapy of greater than 80% and any issue that may have caused a decrease in adherence in the past (i.e. difficulty of dosing schedule, etc.) has been addressed.

If all of the above conditions are met, the request will be approved with a 16-week duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR RE-APPROVAL: · Documentation of current background drug therapy (Fuzeon® is not recommended as monotherapy or to be used without optimal oral therapy). · For the initial reauthorization: documentation submitted of a viral load drop of > 0.7 log decrease from baseline after 12 weeks of starting therapy for requests to continue therapy beyond 16 weeks, or there is documentation provided that the patient has documented clinical improvement (i.e. increased CD4 count) with treatment. · After the initial reauthorization: documentation submitted of current (within the past 30 days) CD4 count and HIV RNA viral load. · If the patient has been on Fuzeon® therapy AND there is an increase of at least 2 log in viral load and/or a 30% decline in CD4 counts from baseline then current phenotype/genotype testing (within the past 30 days) must be submitted to indicate continued susceptibility of the HIV virus to Fuzeon®. If all of the above conditions are met, the request will be approved for up to a 6 month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. FDA INDICATION: Fuzeon® in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection in treatmentexperienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy. DOSAGE AND ADMINISTRATION: The recommended dose of Fuzeon® is 90 mg (1mL) twice daily injected subcutaneously into the upper arm, anterior thigh, or abdomen. In pediatric patients 6 through 16 years of age, the recommended dosage of Fuzeon® is 2mg/kg twice daily up to a maximum dose of 90mg twice daily injected subcutaneously into the upper arm, anterior thigh, or abdomen.

Table 1: NRTIs Generic (Brand; abbreviation) Zidovudine (Retrovir®; AZT, ZDV) NNRTIs Generic (Brand) Nevirapine (Viramune®) under study in neonates Delavirdine (Rescriptor®) Efavirenz (Sustiva®) no data available in children less than 3 years old Etravirine (Intelence®) PIs Generic (Brand) Indinavir (Crixivan®) Misc. Classification Generic (Brand) ENRTY INHIBITORS Celsentri, Maraviroc (Selzentry®) INTEGRASE INHIBITOR Raltegravir (Isentress®)

Didanosine (Videx®; ddI) Zalcitabine (HIVID®; ddC) neonatal dose unknown Tenofovir disoproxil (Viread®) Stavudine (Zerit®; d4T) under study in neonates

Ritonavir (Norvir®) under study in neonates Nelfinavir (Viracept®) under study in neonates Saquinavir (Invirase®-HGC) Lopinavir + Ritonavir (Kaletra®) no data for infants less than 6 months old. For those not receiving concimitant nevirapine or efavirenz Atazanivir (Reyataz®) Tipranavir (Aptivus®)

Lamivudine (Epivir®; 3TC) Abacavir (Ziagen®; ABC) not

approved for infants < 3 months Abacavir/Lamivudine/Zidovudine (Trizivir®) Lamivudine/Zidovudine (Combivir®) Emtriva/Viread (Truvada®)

·

Darunavir (Prezista®)

Indinavir and Saquinavir (PI's) are not FDA approved but have been used in children. Neonatal doses are unknown for both drugs Delavirdine (NNRT) is not approved for use in children. Neonatal and pediatric doses are unknown

·

1. 2. 3. 4. 5. 6. 7. 8.

REFERENCES:

www.aidsinfo.nih.gov. Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents. October 10, 2006. www.aidsinfo.nih.gov. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV-Infected. October 10, 2006. Lalezari J, Henry K, O'Hearn M, et al. Enfuvirtide, and HIV-1 Fusion Inhibitor, for Drug-Resistant HIV Infection in North and South America. New England Journal of Medicine 2003. CDC. MMWR 194; 43(No. RR-12): p. 1-10 www.righto.com/theories/aidsdef.html. 1997 CDC AIDS Definition. www.PAHO.org. Pan American Health Organization (part of WHO). Case Definition-Acquired Immunodeficiency Syndrome (AIDS) NIH Guidelines. Guidelines for the Use of Antiretroviral Agents in HIV Infected Adults and Adolescents. Available from www.hivpositive.com/fDrugAdvisories/NIHguidlinesJune/plasmatesting.html Fuzeon® Prescribing Information, Roche Laboratories, Inc., January 2007.

Revision/Review Date: 2/2009 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgement, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA

GILENYA (fingolimod hcl) capsules: 0.5mg FORMULARY STATUS: Non-formulary PA CRITERIA FOR INITIAL APPROVAL: The member is an adult ( 18 y/o) member with relapsing/remitting MS (RRMS) or secondary progressive MS (SPMS) with a relapsing element. Documentation must be submitted that the patient has had a documented treatment failure to three of the currently marketed Self-Injectable Disease-Modifying Immunomodulating MS Agent (see Box 1 in Glossary for definition of treatment failure) which is consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history, indicating they had received an adequate trial (including dates, doses of 6 months or more of each therapy) or has another documented clinically significant medical reason (intolerance, hypersensitivity, contraindication, etc. Please note that "needle phobia is not an acceptable medical reason) for not taking three out of the following: Copaxone, Rebif , Avonex, Betaseron, or Extavia for a minimum of 6 months each to treat their medical condition. The medication is being recommended and/or prescribed by a neurologist at an FDA approved dosage. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. REAUTHORIZATION CRITERIA: Documentation indicating the member has clinically benefited from therapy. The medication was prescribed at an FDA approved dosage. Medication was recommended by a neurologist and/or prescribed by a neurologist. If all of the above conditions are met, the request will be approved for up to a 12-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. FDA INDICATIONS: Gilenya is indicated for the treatment of patients with relapsing forms of multiple sclerosis (MS) to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability. DOSAGE AND ADMINISTRATION: The recommended dose of Gilenya of 0.5 mg orally once daily. Doses of higher than 0.5 mg are associated with a greater incidence of adverse reactions without additional benefits. BOX 1: TREATMENT FAILURE: A member may be considered to have failed treatment if any of the following are documented: 1. 2. 3. Member who has an attack rate (relapse) of more than 1 per year, fails to show a reduction in relapse rate, or continues to experience attacks (relapses) at a rate similar to that found before starting therapy** Member who has incomplete recovery (cumulative residual abnormalities sustained for 6 months) from repeated attacks, particularly as the EDSS score increases. ** Member experiences an annual increase in the EDSS (Expanded Disability Status Scale) of 1 point from a previous score of 3 to 5.5, or 0.5 point increase from a previous score of 6.0 or greater in the absence of clinical attacks or other documentation of clinically significant disability progression. ** Member who develops new or recurrent brainstem or spinal cord lesions as seen on MRI. ** Members experiencing relapses affecting multiple neurologic symptoms, and those accumulating residual impairments in multiple neurologic systems. ** Members who have progressive motor, cognitive or sensory impairment sufficient to disrupt their daily activities irrespective of changes on neurologic examination, provided the influence of depression, medications or superimposed concurrent disease is ruled out. Examples include: loss of endurance in sustaining activity, forced alterations in activities of daily living, muddled thinking, impaired concentration and mental processing and fatigue. ** Members who have new or enlarging T2 lesions, increase in brain atrophy on MRI, or new T1 Gd enhancing lesions on MRI accompanied by changes in the ability to perform daily activities.**

®

4. 5. 6.

7.

** These are members who have a documented treatment failure after receiving a minimum of 6 months each of a self injectable agent. Diagnostic and/or clinical documentation of treatment failure will be required for the last therapy the member received. This requires that the member has failed a minimum of 6 months of a self-injectable agent or has a documented medical reason (i.e. intolerance) for not utilizing each of these therapies for a minimum of 6 months.

Kurtzke Expanded Disability Status Scale (EDSS) Rating Status Normal Neurological Exam No Disability, minimal symptoms No disability, minimal signs in more than one area Slightly more disability in one area Slightly greater disability in two areas Moderate disability in one area but still walking independently Walking independently but with moderate disability in one area and more than minimal disability in several others 4.0 Walking without aid, self-sufficient, up and about some12 hours a day despite relatively severe disability; able to walk without aid or rest some 500 meters 4.5 Walking without aid, up and about much of the day, able to work a full day, may have some limitation of full activity or require some help, relatively severe disability but able to walk without aid or rest some 300 meters. 5.0 Walking without aid or rest for about 200 meters, disability severe enough to impair full daily activities, can work a full day without special provisions 5.5 Ambulatory without aid or rest for about 100 meters; disability severe enough to prevent full daily activities 6.0 Intermittent or unilateral constant assistance (cane, crutch, brace) required to walk about 100 meters with or without resting 6.5 Needs canes, crutches, braces to walk for 20 meters without resting 7.0 Unable to walk beyond five meters even with aid; mostly confined to a wheelchair; wheels self in standard wheelchair and transfers alone; up and about in wheelchair some 12 hours a day 7.5 Unable to take more than a few steps; restricted to wheelchair; may need aid in transfer; wheels self but cannot carry on in standard wheelchair a full day; may require motorized wheelchair 8.0 Essentially restricted to bed, chair, or wheelchair, but may be out of bed itself much of the day; retains many self-care functions; generally has effective use of arms 8.5 Essentially restricted to bed much of day; has some effective use of arms; retains some self-care functions 9.0 Helpless bed patient; can communicate and eat 9.5 Totally helpless bed patient; unable to communicate effectively or eat/swallow 10.0 Death due to MS Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology.1983;33:1444-1452. REFERENCES: 1. National Multiple Sclerosis Society. Expert Opinion Paper. Medical advisory board of the National MS Society. Treatment recommendations for physicians. Changing therapy in relapsing multiple sclerosis: Considerations and recommendations of a task force of the National MS Society.2004. Available at www.nationalmssociety.org/PRC.asp 2. National Multiple Sclerosis Society. Expert Opinion Paper. Medical advisory board of the National MS Society. Treatment recommendations for physicians. Disease management consensus statement.2005. Available at www.nationalmssociety.org/PRC.asp 3. Cohen BA. Khan O. Jeffery DR. et al. Identifying and treating patients with suboptimal responses. Neurology.2004; 63(Suppl 6):S33-S40. 4. Cohen JA, Barkhof F, Comi Giancarlo C. et al. Oral Fingolimod or Intramuscular Interferon for Relapsing Multiple Sclerosis. The New England Journal of Medicine.2010; 362: 402-15. 5. Kapps L, Antel J, Comi G. Et al. Oral Fingolimod (FTY720) for relapsing Multiple Sclerosis. The New England Journal of Medicine.2006; 355:1124-40. 6. Kappos L, Radue EW, O'Connor P, Et al. A Placebo-Controlled Trial of Oral Fingolimod in Relapsing Multiple Sclerosis. The New England Journal of Medicine. 2010; 362: 387-401. 7. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology.1983;33:1444-1452. 8. Rovaris M. Comi G. Filippi M. MRI markers of destructive pathology in multiple sclerosis-related cognitive dysfunction. Journal of the Neurological Sciences.2006; 245:111-116. 9. Rudick, RA. Lee JC. Simon J. Fisher E. Significance of T2 lesions in multiple sclerosis: A 13-year longitudinal study. Annals of Neurology.2006;60:236-242. 10. Rieckmann P. Toyka KV. Escalating immunotherapy of multiple sclerosis. New aspects and practical application. Multiple Sclerosis Therapy Consensus Group (MSTCG). Journal of Neurology. 2004;251:1329-1339. 11. Leary SM. Porter B. Thompson AJ. Multiple sclerosis: diagnosis and the management of acute relapses. Postgraduate Medicine Journal. 2005;81:302-308. 12. Rio J. Nos C. Tintore M. et al. Assessment of different treatment failure criteria in a cohort of RRMS patients treated with interferon : implications for clinical trials. Annals of Neurology. 2002;52:400-406. 13. Gilenya® Prescribing Information. Novartis, Inc. 9/2010 14. Rosalind C. Kalb, Ph.D., Director, Professional Resource Center, National Multiple Sclerosis Society, "MS Guidelines" 11 August 2004, personal email (11 August, 2004). 0 1.0 1.5 2.0 2.5 3.0 3.5

15. Disease modifying therapies in multiple sclerosis: Report of the Therapeutics and Technology, Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology. 58(2):169-178, January 22, 2002. 16. Morrow T, Brown J, Smith C, Thrower B. Considerations for the treatment of multiple sclerosis in the managed care setting. Formulary 2003; 38 (11). Revision/Review Date: 5/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA FOR GROWTH HORMONE GENOTROPIN CARTRIDGE® 5.8mg (15 units)/vial, and 13.8mg (36 units)/vial GENOTROPIN MINIQUICK® 0.2mg/vial, 0.4mg/vial, 0.6mg/vial, 0.8mg/vial, 1.0mg/vial, 1.2mg/vial, 1.4mg/vial, 1.6mg/vial, 1.8mg/vial , and 2.0mg/vial HUMATROPE® 5mg/vial HUMATROPE CARTRIDGE® 6mg/cartridge, 12mg/cartridge, 24mg/cartridge NORDITROPIN® 4mg/vial, 8mg/vial NORDITROPIN CARTRIDGE® 5mg/1.5ml, 15mg/1.5ml NORDITROPIN NORDIFLEX® 5mg/1.5ml, 10mg/1.5ml, 15mg/1.5ml OMNITROPETM 1.5mg/vial, 5.8mg/vial NUTROPIN® 5mg/vial, 10mg/vial NUTROPIN AQ® 5mg/vial, 10mg/vial SAIZEN® 5mg/vial, 8.8mg/vial, 8.8mg/cartridge TEV-TROPIN® 5mg/vial PA CRITERIA FOR APPROVAL: · The physician has written for a FDA approved indication or other medically accepted use as per compendia (Drug Points, Micro Medix, American Hospital Formulary System, Package Insert). AND · For patients with growth hormone deficiency states (adult and pediatric) either the appropriate information, diagnosis &/or laboratory information has been provided with the request. This includes Growth Hormone (GH) level in response to the preferred stimulatory test (i.e. Insulin Tolerance Test or Glucagon or Arginine) and Insulin Growth Factor 1 level indicative of GH deficiency. In addition, for pediatric patients, documentation of his or her growth velocity (below 4.5 cm/year), their height percentile for age and gender, how far below the standard deviation (SD) their height is for their age (at least 2 SD below normal), or how far below the SD their height is from their mid-parent height percentile (at least 2 SD below) (please see table below for additional information). AND · · · The medication is recommended and prescribed by an endocrinologist AND The medication is being prescribed at an appropriate dose AND If the patient is 17 or older and was diagnosed with childhood onset growth hormone deficiency, and documentation was provided that GH therapy is still medically necessary despite a 1-3 month trial off the medication (GH therapy discontinued for 1-3 months and resulting GH/IGF-1 levels are low). AND · If the patient is 17 or older and still requires GH therapy and is receiving childhood dosing versus lower adult dosing, appropriate documentation was provided (i.e. patient has not reached maximum predicted height or is still having clinical response) documenting the medical necessity of childhood GH dosing. AND · If the request for is not for Genotropin or Norditropin brand growth hormone, the provider submitted a documented medical reason (i.e. intolerance) why it is medically necessary to utilize some other brand formulation (Humatrope, Nutropin, Omnitrope etc.) of Growth Hormone.

If all of the above conditions are met, the request will be approved with a 12-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested.

DIAGONOSIS AND TESTING INFORMATION: Diagnosis Turner's Syndrome, Prader-Willi Syndrome, & Noonan Syndrome Children with Chronic Renal Insufficiency Information Required Documented short statue for age and sex Documented short statue for age and sex. For patients with short statue or growth failure associated with chronic renal insufficiency in patients with chronic renal failure or end-state renal disease up to the time of renal transplantation. Documented short statue for age and sex. The patients is at least 2 years old and documentation of the patient's birth weight being less than 2500g at a gestational age of 37 weeks or more OR a birth weight or length below the 3rd percentile for gestational age Growth Hormone Testing Required N/A N/A

Children who are Small for Gestation Age (SGA)

N/A

MEDICALLY ACCEPTED INDICATIONS: ADULTS For the replacement of endogenous growth hormone in adults with growth hormone deficiency who meet either of the following 2 criteria: · · Adult onset: Patients who have growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. Childhood onset: Patients who were growth hormone deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes.

CHILDREN: · Growth failure due to an inadequate secretion of endogenous growth hormone. · Growth failure due to Prader-Willi syndrome. Confirm the diagnosis of Prader-Willi syndrome by appropriate genetic testing (Genotropin & Omnitrope Only). · Growth failure in children born small for gestational age who fail to manifest catch-up growth by 2 years of age. · Growth failure associated with Noonan syndrome and Turner syndrome in patients who have open epiphyses. · For the treatment of idiopathic short stature, also called non­growth-hormone-deficient short stature, defined by height standard deviation score less than or equal to -2.25, and associated with growth rates unlikely to permit attainment of adult height in the normal range, in children whose epiphyses are not closed and for whom diagnostic evaluation excludes other causes associated with short stature that should be observed or treated by other means. · For the treatment of growth failure associated with chronic renal function impairment up to the time of renal transplantation. · For the treatment of short stature or growth failure in children with short stature homeoboxcontaining gene (SHOX) deficiency whose epiphyses are not closed DOSAGE AND ADMINISTRATION: ADULTS: up to 0.15-0.30 mg/day or up to 0.0125 mg/kg/day CHILDREN: Chronic renal insufficiency (CRI): up to 0.35 mg/kg/week divided into daily SC injections is recommended. Therapy may be continued up to the time of renal transplantation. Growth Hormone deficiency: up to 0.3mg/kg/week Noonan's Syndrome: up to 0.066 mg/kg/day Prader-Willi syndrome: up to 0.24mg/kg/week Short for gestational age: up to 0.48mg/kg/week

Turner syndrome: up to 0.375 mg/kg/week (1.125 IU/kg) of body weight administered by SC injection is recommended. Divide into equal doses given either daily or on 3 alternate days. REFERENCES: 1. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for Growth Hormone Use in Adults and Children- 2009 Update. Endocrine Practice Vol 15 (Suppl 2) September/October 2009. Facts and Comparisons. Growth Hormone Product information, 2002 Genotropin Package Insert. Pharmacia & Upjohn Co, Pfizer Inc. New York, NY, August 2009. Humatrope Package Insert. Eli Lilly and Company. Indianapolis, IN. August 2009. Norditropin Package Insert. Novo Nordisk Inc. Princeton, NJ. November 2008. Nutropin Package Insert. Genetech Inc. San Francisco, CA. January 2008. Omnitrope Package Insert. Sandoz Inc. Princeton, NJ. June 2010. Saizen Package Insert. EMD Serono Inc. Rockland, MA. September 2007. Tev-Tropin Package Insert. Gate Pharmaceuticals. Sellersville, PA. October 2007.

2. 3. 4. 5. 6. 7. 8. 9.

Revision/Review Date: 12/2011 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgement, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION PROTOCOL FOR GONADOTROPIN RELEASING HORMONE AGONISTS (GnRH)

Leuprolide Acetate (Lupron®) injection 5 mg/mL (2.8 mL) Lupron Depot®: 3.75 mg, 7.5 mg Lupron Depot®-3 Month: 11.25 mg, 22.5 mg Lupron Depot®-4 Month: 30 mg Lupron Depot-Ped®: 7.5 mg, 11.25 mg, 15 mg Leuprolide Acetate (Eligard®) 7.5 mg, 22.5 mg, 30 mg, 45 mg Firmagon®: 80mg and 120mg vial Goserlin (Zoladex®): 3.6 mg, 10.8 mg Triptorelin Pamoate (Trelstar Depot®/Trelstar LA®) 3.75 mg(Trelstar Depot) and 11.25 mg(Trelstar LA) Histrelin Acetate (Vantas Implant®) 50 mg Supprelin® LA 50 mg Degarelix® (Degarelix Acetate) 80 mg, 120 mg Newly Marketed Gondaotropin Releasing Hormone Agonist:

Initial Approval: · The request for the medication is for an Food and Drug Administration (FDA) approved indication, and/or is used for a medical condition that is supported by the medical compendium (Micromedex, American Hospital Formulary Service (AHFS), Drug Points, Drug Package Insert) as defined in the Social Security Act 1927 and/or per the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), The American College of Obstetricians and Gynecologists (ACOG), or the American Academy of Pediatrics (AAP) standard of care guidelines. If the medication request is for the treatment of central precocious puberty (CPP) patient may be authorized either Lupron-Depot Ped® OR Supprelin LA® for the treatment of the condition as long as there is a clinical diagnosis of CPP with onset of secondary sexual characteristics less than age 8 in females and age 9 in males and ALL of the following apply to the patient: 1. Diagnosis is confirmed by a pubertal response to a GnRH stimulation test, bone age advanced 1 year beyond chronicle age. 2. There are documented baseline evaluations (including ultrasound, CT, MRI, and laboratory levels) to rule out a tumor. For all other indications, if the medication request is for any other GnRH agonist other than Lupron®, the patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) treatment failure after receiving an adequate trial (including dates of 3 months or more of therapy) of Lupron® and/or has another documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not utilizing Lupron® to treat their medical condition. If the medication request is for the treatment of advanced prostate cancer (Stage III or Stage IV) then the patient most be an adult male (18 y/o). If the medication request is for the treatment of a confirmed diagnosis of endometriosis, the patient is an adult female (18 y/o) who does not have documented Osteoporosis. If the medication request is for the treatment of fibroids, the patient is an adult female (18 y/o) and ONE of the following apply to the patient: 1. The patient is anemic (Hgb < 10.2 g/dl or Hct of < 30%) attributed to fibroids and the patient has had a one to three month trial of iron therapy alone which is (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) to try and correct the anemia or there is a medical reason (intolerance, hypersensitivity, contraindication, etc) for not using iron alone to manage the anemia. 2. The patient requires the medication to decrease uterine volume as a result of uterine fibroids to manage symptoms (i.e. pelvic pressure, pelvic fullness, urinary frequency, nocturia, constipation and/or anemia) and for shrinkage of size to allow surgical intervention.

·

·

· · ·

· ·

If the medication request is for the treatment of endometrial thinning, documentation was submitted indicating the patient is scheduled for endometrial ablation for dysfunctional uterine bleeding. Prescribed dosing of GnRH agonist is within FDA approved indications and/or is supported by the medical compendium as defined by the Social Security Act and/or per the NCCN, ASCO, ACOG or AAP standard of care guidelines. The medication is recommended and prescribed by a specialist in the field to treat the patient's respective medical condition

·

If all of the above conditions are met, the request will be approved for up to 6 months for treatment of prostate/breast cancer or central precocious puberty and up to 3 months or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per the NCCN, ASCO, ACOG or AAP standard of care guidelines; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Reauthorization of Medication: · The prescribing physician has provided documentation as to the clinical benefits of the medication supporting continued treatment, OR the medication is being continued in accordance with the recommended time as defined by FDA drug package insert, and/or per recommendations of the medical compendium as described above, and/or per the NCCN, ASCO, ACOG or AAP standard of care guidelines. If the medication reauthorization is for endometriosis ALL of the following apply to the patient: 1. If the request is for a continuation of treatment exceeding 6 months, the patient is receiving or will be prescribed "add back" hormonal therapy (norethindrone acetate 5 mg daily or conjugated estrogen therapy) {consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history}, OR if the patient has a documented medical reason for not being able to take "add back" therapy, the patient is receiving or is intended to receive anti-osteoporosis therapy (e.g. alendronate or risedronate) {consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history}. 2. If the patient received > 6 to 11 months cumulative doses of the GnRH agonist a Dexa scan was performed and the results were submitted with the medication request, indicating that the patient does not have documented Osteoporosis AND the patient is receiving calcium supplementation (1200 mg/day) and vitamin D (400-800 units/day), which is (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history). 3. The patient has not received cumulative doses of the GnRH agonist up to or greater than 12 months of therapy. If the medication reauthorization is for fibroids, the patient has not received cumulative doses of the GnRH agonist up to or greater than 6 months of therapy. If the medication reauthorization is for central precocious puberty, the child is male and < 12 years or female and < 11 years of age OR the child is male and is > 12 years of age or a female that is > 11 years of age, and has an acceptable documented medical reason to continue treatment. The medication is recommended and prescribed by a specialist in the field to treat the member's respective medical condition Prescribed dosing of medication is within FDA approved indications and/or supported by the medical compendium as defined by the Social Security Act and/or per the NCCN, ASCO, ACOG or AAP standard of care guidelines.

·

· ·

·

·

If all of the above conditions are met, the request will be approved for up to 6 months for treatment of prostate/ breast cancer or central precocious puberty and up to 3 months or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per the NCCN, ASCO, ACOG or AAP standard of care guidelines; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. FDA Approved Indications and Dosing:

Leuprolide Acetate (Lupron®), Lupron Depot®, Lupron Depot-Ped®: · Endometriosis (decrease pain/lesions): 11.25mg IM Q 3months x 6 months; 3.75mg IM Q month x 6 months · Prostate Cancer-Advanced: 1mg SC once a Day (available generically); 22.5mg IM Q3months o 30mg IM Q4months; 7.5mg IM once a month · Uterine Leiomyoma (Fibroids): 11.25mg IM 3 months depot x 1; 3.75mg IM once a month x 3mos · Central Precocious Puberty (CPP): For injection: 50mcg/kg/day SC x 1 dose, if down regulation is not achieved, repeat by titrating dose up by 10mcg/kg/day to final titrated maintenance dose. May be administered by a patient/parent or health care professional; For depot: give 300mcg/kg (Min dose 7.5mg) IM Q4 wks as depot x 1 injection, if down regulation is not achieved, repeat by titrating dose up by 3.75mg Q4wks, the final titrated dose is the maintenance dose). Must be administered under physician supervision.

Leuprolide Depot Starting Dose for CPP Weight (kg) Dose (mg) <= 25 > 25 to 37.5 > 37.5 7.5 11.25 15

·

Breast Cancer: 3.75mg IM once a month; 11.25mg IM Q3months

Leuprolide Acetate (Eligard®) · Prostate Cancer-Advanced: 7.5mg SC once a month; 22.5mg SC Q3months; 30mg SC Q4months; 45mg SC Q6months Firmagon®: · Advanced Prostate Cancer: 240mg given once (as two injections of 120mg each) followed by a single 80mg injection once every 28 days. Goserlin (Zoladex®) · Breast Cancer: 3.6mg SC Q28 days long term · Endometriosis (decrease pain/lesions): 3.6mg SC Q28 days x 6months · Hypoplasia of Endometrium (thinning agent): 3.6mg SC 4 wks prior to ablation surgery; 3.6mg SC given 4 wks apart w/2nd inject given 2-4wks before ablation · Prostate Cancer- Advanced: 3.6mg SC Q28 days, 10.8mg SC Q3mos long term · Prostate Cancer-stageB2-C local: 3.6mg SC then in 28days 10.8mg SC 8 wks prior to XRT in combination with flutamide; 3.6mg Q28 days x 4 (2 prior/2 during XRT) Triptorelin Pamoate (Trelstar Depot®/Trelstar LA®) · Prostate Cancer- Advanced: 3.75mg IM Q month; 11.75mg IM Q84 days Histrelin Acetate (Vantus Implant®) · Prostate Cancer- Advanced: 50mg SC Q12 months Supprelin® LA · Central precocious puberty: 1 implant (50mg) every 12 months Degarelix® · Advance Prostate Cancer: a starting dose of 240 mg injection (given as two 120 mg shots) then followed by 80 mg every 28 days. * Note: Use of these medications to promote fertility, is not a covered benefit under the Medical Assistance Program, except when prescribed for certain diagnosis, such as regulation of menstrual cycle. References:

1. The American College of Obstetricians and Gynecologists. ACOG Practice Bulletin: Medical management of endometriosis. International Journal of Gynecology & Obstetrics. 2000;71:183-196. Bulletin Number 11, December 1999 (Replaces Technical Bulletin Number 184, September 1993. The American College of Obstetricians and Gynecologists Committee on Adolescent Health Care. Committee Opinion: Endometriosis in Adolescents. Obstetrics & Gynecology. 2005;105:921-927. ACOG Committee Opinion Number 310, April 2005. Kohn B. Julius JR. Blethen SL. Combined use of growth hormone and gonadotropin-releasing hormone analogues: the National Cooperative Growth Study Experience. National Cooperative Growth Study: Guidance in Growth: Proceedings of the National Cooperative Growth Study Twelfth Annual Investigators Meeting in New Orleans, LA. American Academy of Pediatrics. 1999;104(4)Supplement to Pediatrics, Part2 of 2:1014-1017. Walvord EC. Pescovitz OH. Combined use of growth hormone and gonadotropin-releasing hormone analogues in precocious puberty: theoretic and practical considerations. National Cooperative Growth Study: Guidance in Growth: Proceedings of the National

2. 3.

4. 5.

6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26.

Cooperative Growth Study Twelfth Annual Investigators Meeting in New Orleans, LA. American Academy of Pediatrics. 1999;104(4)Supplement to Pediatrics, Part2 of 2:1010-1014. Elders MJ. Scott CR. Frindik JP. Kemp SF. Clinical workup of precocious puberty. The Lancet.1997;350(9076):457-458. Kaplowitz PB. Oberfield SE. The Drug and Therapeutics and Executive Committees of the Lawson Wilkins Pediatric Endocrine Society. Special Article. The American Academy of Pediatrics. Pediatrics. 1999;104(4, Part 1 of 2): 936-941. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Breast Cancer. Version 2.2006. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Prostate Cancer. Version 2.2005. Hall MC. Fritzsch RJ. Sagalowsky AI. Et al. Prospective determination of the hormonal response after cessation of luteinizing hormone-releasing hormone agonist treatment in patients with prostate cancer. Urology. 1999:53(5):898-902. Kimura K. Markowski M. Bowen C. Gelmann EP. Androgen blocks apoptosis of hormone-dependent prostate cancer cells. Cancer Research.2001;61:5611-5618. Shahidi M. Norman AR. Gadd J. et al. Recovery of serum testosterone, LH and FSH levels following neoadjuvant hormone cytoreduction and radical radiotherapy in localized prostate cancer. Clinical Oncology. 2001;13:291-295. Seidenfeld J. Samson DJ. Hasselblad V. et al. Single therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis. Annals of Internal Medicine.2000;132:566-577. Lupron Product Information. TAP Pharmaceutical Products Inc. 12/07. Lupron Depot-Ped Product Information. TAP Pharmaceutical Products Inc. 12/07. Lupron Depot-4 Month 30mg Product Information. TAP Pharmaceutical Products Inc. 12/07. Lupron Depot-3 Month 22.5mg Product Information. TAP Pharmaceutical Products Inc. 12/07. Lupron Depot-3 Month 11.25mg Product Information. TAP Pharmaceutical Products Inc. 12/07. Lupron Depot 3.75mg Product Information. TAP Pharmaceutical Products Inc. 12/07. Lupron Depot 7.5mg Product Information. TAP Pharmaceutical Products Inc. 12/07. Firmagon® Package Insert. Ferring Pharmaceuticals. Parsippany, NJ. February 2009. Eligard® Package Insert. Sanofi-Aventis. Fort Collins, CO. 2.2008. Zoladex® 3.6 mg and 10.8mg Package Insert. Astra Zeneca. Wilmington, DE. August 2009. Telestar® LA and Telestar® Depot Package Insert. Watson Pharma, Inc. Corona, CA. August 2006. Vantus® Package Insert. Indevus Pharmaceuticals, Inc. Lexington, MA. May 2009. Supprelin® Package Insert. Indevus Pharmaceuticals, Inc. Lexington, MA. June 2009.

Revision/Review Date: 05/2010 Associated Policy: Prior Authorization of Medications 236.200

NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION PROTOCOL FOR HEPATITIS B & C TREATMENT Pegasys® (peginterferon alfa-2a): 180mcg/ml single use glass vials or prefilled syringe PegIntron® (peginterferon alfa-2b): 50mcg/0.5mL, 80mcg/0.5mL, 120mcg/0.5mL powder for injection in Redipens® or glass vials Copegus® (ribavirin): 200mg tablet Rebetol® (ribavirin): 200mg capsule IncivekTM (telaprevir): 375mg tablets Victrelis® (boceprevir): 200mg capsule FORMULARY STATUS: PEGASYS® and RIBAVIRIN TABLETS PREFERRED PA CRITERIA FOR APPROVAL FOR THE TREATMENT OF HEPATITIS C OR HEPATITIS B INFECTION: Place the patient into one of the following categories: Treatment naïve for Hepatitis C infection go to Section A Treatment naïve using the three medicine treatment regimen for Hepatitis C infection go to Section B Monotherapy with peginterferon alfa for patients who failed previous treatment regimens go to Section C Reauthorization after 12 - 16 weeks of treatment for Hepatitis C go to Section D Reauthorization after 12 - 16 weeks of treatment with three medicine regimen (using Incivek) for Hepatitis C go to Section E Reauthorization after 28 weeks of treatment with three medicine regimen (using Incivek) for Hepatitis C go to Section F Reauthorization after 8 -12 weeks of treatment with three medicine regimen (using Victrelis) for Hepatitis C go to Section G Patient failed standard non-pegylated interferon alpha combined with ribavirin for the treatment of Hepatitis C go to Section H Patient using a three medicine regimen who has failed standard non-pegylated interferon alpha combined with ribavirin for the treatment of Hepatitis C go to Section I Reauthorization after 12 - 16 weeks of treatment with three medicine regimen (with Incivek) for patients who failed interferon alpha combined with ribavirin for the treatment of Hepatitis C go to Section J Reauthorization after 28 weeks of treatment with three medicine regimen (with Incivek) for patients who failed interferon alpha combined with ribavirin for the treatment of Hepatitis C go to Section K Reauthorization after 8 -12 weeks of treatment with three medicine regimen for patients who failed interferon alpha combined with ribavirin for the treatment of Hepatitis C go to Section L Treatment of Hepatitis B go to Section M

-

Section A: PA Criteria for authorization for treatment naïve patients with Hepatitis C · · · · · The appropriate lab-work was provided with the request including HCV RNA viral load (result within one month of starting therapy), liver function studies (result within one month of starting therapy) and genotype. The patient's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are abnormal or the patient has a liver biopsy result (greater than Ishak stage 0-2 or Metavir, IASL, and Batts-Ludwig stage 0-1-see table 10) or another noninvasive procedure that shows the patients has advanced to severe fibrosis. If the patient has HIV co-infection and ONE of the following apply then documentation of that patient's CD4+ T cell count and HIV RNA must be submitted (lab results within one month of starting therapy) The patient does not have a history of kidney, heart, or other solid-organ transplant (excluding liver transplant). The dose that has been prescribed for the patient is consistent with the dosing recommendations listed below and is prescribed by a hepatologist, gastroenterologist, infectious disease specialist, or other specialist experienced in the treatment of Hepatitis C.

·

If the medication request is for a pegylated interferon alpha product other than Pegasys®, the patient has a documented medical reason (pediatric patient, intolerance, hypersensitivity, contraindication, etc) other than treatment failure for not using Pegasys® to treat their medical condition.

If all of the above conditions are met, and the patient has Genotype 1, 4 or 6 or the patient has Genotype 2 or 3 and is co-infected with HIV, the request will be approved for a 16-week duration; if the patient has Genotype 2 or 3 and is not co-infected with HIV, the request will be approved for 24 weeks of therapy, if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section B: PA Criteria for authorization for treatment naïve patients with Hepatitis C and will be treated with triple combination therapy: · · · · · The patient is an adult (> 18y/o) and the appropriate lab-work was provided with the request including HCV RNA viral load (result within one month of starting therapy), liver function studies (result within one month of starting therapy) and genotype 1 infection. The patient's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are abnormal or the patient has a liver biopsy result (greater than Ishak stage 0-2 or Metavir, IASL, and Batts-Ludwig stage 0-1-see table 10) or another noninvasive procedure that shows the patient has advanced to severe fibrosis. The patient does not have a history of kidney, heart, or other solid-organ transplant. If the medication request is for a pegylated interferon alpha product other than Pegasys®, the patient has a documented medical reason (pediatric patient, intolerance, hypersensitivity, contraindication, etc) other than treatment failure for not using Pegasys® to treat their medical condition. The dose that has been prescribed for the patient is consistent with the dosing recommendations listed below and is prescribed by a hepatologist, gastroenterologist, infectious disease specialist or other specialist experienced in the treatment of Hepatitis C.

If the request is for triple combination therapy with Incivek and all of the above conditions are met, and the request for peginterferon alfa and ribavirin request will be approved for a 16-week duration and Incivek will be approved for an 12 week duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. or If the request is for triple combination therapy with Victrelis and all of the above conditions are met, and the request for peginterferon alfa and ribavirin request will be approved for a 16-week duration and Victrelis will be approved for an 12 week duration. If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section C: PA Criteria for authorization of monotherapy with peginterferon alfa for patients who failed previous treatment regimens for Hepatitis C · · · The patient has failed up to 48 weeks of interferon or peg-interferon alpha therapy alone and has a medical reason for not receiving combination therapy with a peginterferon alpha and ribavirin, or the patient failed combination therapy with ribavirin and interferon or ribavirin and peginterferon alpha. The appropriate lab-work was provided with request including HCV RNA viral load (result within one month of starting therapy), liver function studies (result within one month of starting therapy) and genotype. The patient's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are abnormal and/or the patient has a liver biopsy result (greater than Ishak stage 0-2 or Metavir, IASL, and Batts-Ludwig stage 0-1-see table 10) or another noninvasive procedure that shows the patients has advanced to severe fibrosis. The provider submitted documentation that the patient has advanced liver disease (stage 3 or 4 fibrosis and/or cirrhosis) and had documented clinical benefit (improvement in extra-hepatic signs and symptoms) while receiving an interferon (pegylated or non-pegylated interferon) based therapy and upon stopping therapy resulted in clinical worsening of extra-hepatic signs and symptoms OR

·

· · ·

documentation was submitted that the patient has clinical extra-hepatic signs or symptoms (cryoglobulinemia, glomerulonephritis ­ see table 2) that improved while on interferon based therapy and worsened while off therapy despite not eradicating the Hepatitis C virus. The patient does not have a history of kidney, heart, or other solid-organ transplant (excluding liver transplant) The dose that has been prescribed for the patient is consistent with the dosing recommendations listed below and is prescribed by a hepatologist, gastroenterologist, infectious disease specialist, or other specialist experienced in the treatment of Hepatitis C. If the medication request is for a pegylated interferon alpha product other than Pegasys®, the patient has a documented medical reason (pediatric patient, intolerance, hypersensitivity, contraindication, etc) other than treatment failure for not using Pegasys® to treat their medical condition.

If all of the above conditions are met, the request will be approved for a 16-week duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section D: PA Criteria for authorization for patients who received treatment for 12-16 weeks of therapy for Hepatitis C · · · Appropriate lab work was forwarded with the request (repeat HCV load, liver function test including ALT/AST) dated 12 weeks after starting therapy to evaluate initial response to medication. The patient has responded to treatment (complete eradication of HCV RNA levels or > 2 log decrease in HCV RNA viral load after receiving 12-16 weeks of therapy) The patient is a non-responder (less than 2 log drop in HCV RNA levels after 12-16 weeks of therapy) and the patient has documented advanced liver disease (stage 3 or 4 fibrosis or cirrhosis) and the prescribing physician provided documentation of improvement and benefit of treatment (normalization of liver ALT/AST levels if levels were abnormally elevated prior to starting treatment and/or improvement in clinical signs/symptoms of Hepatitis C infection). The patient does not have a history of kidney, heart, or other solid-organ transplant (excluding liver transplant). The dose that has been prescribed for the patient is consistent with the dosing recommendations listed below and is prescribed by a hepatologist, gastroenterologist, infectious disease specialist, or other specialist experienced in the treatment of Hepatitis C.

· ·

If all of the above conditions are met, the request will be approved for up to a 48-week total duration for Genotypes 2 and 3 HIV co-infected, Genotype 1, 6 and 4; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section E: PA Criteria for reauthorization for treatment naïve patients who received treatment with the three medicine regimen (with Incivek) after 12-16 weeks of therapy for Hepatitis C · · Appropriate lab work was forwarded with request (repeat HCV load, liver function test including ALT/AST) dated 4 and 12 weeks after starting therapy to evaluate initial response to medication. If the patient has a detectable HCV-RNA level (but less than 100 IU/ml) at treatment week 4 or 12 then an additional 12 weeks of peginterferon alfa and ribavirin treatment will be approved and repeat laboratory results will need to be submitted. · PLEASE NOTE: a confirmed `detectable but below limit of quantification' HCV-RNA result should not be considered equivalent to an "undetectable" HCV-RNA result. Please see the Laboratory Test section in the dosage and administration section of Incivek for more information. and · Please see the table entitled "Recommended Treatment Duration" for additional information. If the patient has a detectable HCV-RNA level (greater than 100 IU/ml) at treatment week 4 or 12 then both Incivek and the peginterferon alfa and ribavirin therapy must be discontinued and NO FURTHER TREATMENT WILL BE APPROVED.

·

·

The dose that has been prescribed for the patient is consistent with the dosing recommendations listed below and is prescribed by a hepatologist, gastroenterologist, infectious disease specialist, or other specialist experienced in the treatment of Hepatitis C.

If all of the above conditions are met, and the patient has undetectable HCV-RNA levels after 4 and 12 weeks of treatment the request for the peginterferon and ribavirin will be approved with 8-week duration (or a total of 24 weeks of treatment), OR a detectable levels (but a HCV-RNA level of less than 1000 IU/mL) after 4 or 12 weeks of treatment, the request for the peginterferon and ribavirin will be approved with a 12-week duration (or a total of 28 weeks of treatment), NO FURTHER TREATMENT WITH INCIVEK WILL BE APPROVED. If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section F: PA Criteria for reauthorization for treatment naïve patients who received treatment with the three medicine regimen (with Incivek) after 28 weeks of therapy for Hepatitis C · · Appropriate lab work was forwarded with the request (repeat HCV load, liver function test including ALT/AST) dated 24 weeks after starting therapy to evaluate response to medication. If the patient has a detectable HCV-RNA level at treatment week 24 then the peginterferon alfa and ribavirin therapy must be discontinued and NO FURTHER TREATMENT WILL BE APPROVED. · PLEASE NOTE: a confirmed `detectable but below limit of quantification' HCV-RNA result should not be considered equivalent to an "undetectable" HCV-RNA result. Please see the Laboratory Test section in the dosage and administration section of Incivek for more information. and · Please see the table entitled "Recommended Treatment Duration" for additional information. The dose that has been prescribed for the patient is consistent with the dosing recommendations listed below and is prescribed by a hepatologist, gastroenterologist or other specialist experienced in the treatment of Hepatitis C.

·

If all of the above conditions are met, and the patient has undetectable HCV-RNA levels after 24 weeks of treatment, the request for the peginterferon and ribavirin will be approved for a 20-week duration (or a total of 48 weeks of treatment). If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section G: PA Criteria for reauthorization for treatment naïve patients who received treatment with the three medicine regimen (with Victrelis) for 12-16 weeks of therapy for Hepatitis C · · Appropriate lab work was forwarded with the request (repeat HCV load, liver function test including ALT/AST) dated 8, 12 and 24 weeks after starting therapy to evaluate the initial response to medication. If the patient has a HCV-RNA level greater than 100 IU/ml at week 12 of treatment or a detectable HCVRNA at treatment week 24 the three medicine regimen will be discontinued and no further reauthorizations will be given. · PLEASE NOTE: a confirmed `detectable but below limit of quantification' HCV-RNA result should not be considered equivalent to an "undetectable" HCV-RNA result. Please see the Laboratory Test section in the dosage and administration section of Victerlis for more information. and · Please see the table entitled "Duration of Therapy Using Response-Guided Therapy Guidelines in Patients without cirrhosis" for additional information. The dose that has been prescribed for the patient is consistent with the dosing recommendations listed below and is prescribed by a hepatologist, gastroenterologist, infectious disease specialist, or other specialist experienced in the treatment of Hepatitis C.

·

If all of the above conditions are met, and the patient has undetectable HCV-RNA levels after 8 and 12 weeks of treatment, the request will be approved for a 12-week duration (or a total of 28 weeks of treatment) OR if the patient has cirrhosis then the request for all three medications will be approved for a 32 week duration (or a total of 48 weeks). NO FURTHER APPROVALS WILL BE NEEDED. If the patient has detectable levels after 8 weeks of treatment but then a HCV-RNA level of less than 100 IU/mL after 12 weeks of treatment, then the

three medicine regimen will be approved for the 16 weeks of therapy (or a total of 28 weeks of treatment). THEN If these patients then have an undetectable HCV-RNA level after 24 weeks of treatment then Victrelis will be approved for 8 weeks of therapy (or a total of 36 weeks of treatment) and the peginterferon alfa and ribavirin therapy will be approved for 20 weeks of treatment (or a total of 48 weeks of treatment) OR if the patient has cirrhosis then the request for all three medications will be approved for a 20 week duration (or a total of 48 weeks). NO FURTHER APPROVALS WILL BE NEEDED. If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section H: PA Criteria for authorization for peginterferon alfa and ribavirin for Patients who failed standard interferon combined with ribavirin for Hepatitis C · The patient was treated with standard interferon and ribavirin and had an end of treatment response (complete viral eradication) and subsequently relapsed after therapy, or the member was a nonresponder to interferon and ribavirin but has genotype 2 or 3 HCV or the patient has documented advanced liver disease (stage 3 or 4 fibrosis or cirrhosis) with clinical symptoms and/or extrahepatic manifestations of Hepatitis C infection. The appropriate lab-work was provided with the request including HCV RNA viral load (result within one month of starting therapy), liver function studies (result within one month of starting therapy) and genotype. The patient's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are abnormal and/or the patient has a liver biopsy result (greater than Ishak stage 0-2 or Metavir, IASL, and Batts-Ludwig stage 0-1-see table 10) or another noninvasive procedure that shows the patients has advanced to severe fibrosis. The patient does not have a history of kidney, heart, or other solid-organ transplant (excluding liver transplant) The dose that has been prescribed for the patient is consistent with the dosing recommendations listed below and is prescribed by a hepatologist, gastroenterologist, infectious disease specialist, or other specialist experienced in the treatment of Hepatitis C. If the medication request is for a pegylated interferon alpha product other than Pegasys®, the patient has a documented medical reason (pediatric patient, intolerance, hypersensitivity, contraindication, etc) other than treatment failure for not using Pegasys® to treat their medical condition.

· ·

· · ·

If all of the above conditions are met, the request will be approved for a 16-week duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section I: PA Criteria for authorization for the three medicine regimen for Patients who failed standard interferon combined with ribavirin for Hepatitis C · The patient is an adult (> 18y/o) and has genotype 1 infection and was treated with standard interferon and ribavirin and had an end of treatment response (complete viral eradication) and subsequently relapsed after therapy, partial response, or failed previous treatment. Including documentation of the patient's HCV-RNA levels to confirm either relapse, partial response, or failure on previous treatment The appropriate lab-work was provided with the request including HCV-RNA viral load (result within one month of starting therapy), liver function studies (result within one month of starting therapy) and genotype 1 infection. The patient's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are abnormal and/or the patient has a liver biopsy result (greater than Ishak stage 0-2 or Metavir, IASL, and Batts-Ludwig stage 0-1-see table 10) or another noninvasive procedure that shows the patients has advanced to severe fibrosis. The patient does not have a history of kidney, heart, or other solid-organ transplant. If the medication request is for a pegylated interferon alpha product other than Pegasys®, the patient has a documented medical reason (pediatric patient, intolerance, hypersensitivity, contraindication, etc) other than treatment failure for not using Pegasys® to treat their medical condition.

· ·

· ·

·

The dose that has been prescribed for the patient is consistent with the dosing recommendations listed below and is prescribed by a hepatologist, gastroenterologist, infectious disease specialist or other specialist experienced in the treatment of Hepatitis C.

If the request is for triple combination therapy with Incivek and all of the above conditions are met, and the request for peginterferon alfa and ribavirin request will be approved for a 16-week duration and Incivek will be approved for an 12 week duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. or If all of the above conditions are met, then the request for peginterferon alfa and ribavirin request will be approved for a 16-week duration and Victrelis will be approved for an 12 week duration. If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section J: PA Criteria for reauthorization for treatment experienced patients who received treatment with a three medicine regimen (with Incivek) after 12-16 weeks of therapy for Hepatitis C · · Appropriate lab work was forwarded with the request (repeat HCV load, liver function test including ALT/AST) dated 4 and 12 weeks after starting therapy to evaluate initial response to medication. If the patient has a detectable HCV-RNA level (but less than 1000 IU/ml) at treatment week 4 or 12 then an additional 8 weeks of peginterferon alfa and ribavirin treatment will be approved and repeat laboratory results will need to be submitted. · PLEASE NOTE: a confirmed `detectable but below limit of quantification' HCV-RNA result should not be considered equivalent to an "undetectable" HCV-RNA result. Please see the Laboratory Test section in the dosage and administration section of Incivek for more information. and · Please see the table entitled "Recommended Treatment Duration" for additional information. If the patient has a detectable HCV-RNA level (greater than 1000 IU/ml) at treatment week 4 or 12 then both Incivek and the peginterferon alfa and ribavirin therapy must be discontinued and NO FURTHER TREATMENT WILL BE APPROVED. The dose that has been prescribed for the patient is consistent with the dosing recommendations listed below and is prescribed by a hepatologist, gastroenterologist, infectious disease specialist, or other specialist experienced in the treatment of Hepatitis C.

· ·

If all of the above conditions are met, and the patient has undetectable HCV-RNA levels after 4 and 12 weeks of treatment the request for the peginterferon and ribavirin will be approved for an 8-week duration (or a total of 24 weeks of treatment), OR a detectable level(but a HCV-RNA level of less than 1000 IU/mL) after 4 or 12 weeks of treatment, the request for the peginterferon and ribavirin will be approved for a 12-week duration (or a total of 28 weeks of treatment), NO FURTHER TREATMENT WITH INCIVEK WILL BE APPROVED. If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section K: PA Criteria for reauthorization for treatment experience patients who received treatment the three medicine regimen (with Incivek) after 28 weeks of therapy for Hepatitis C · · Appropriate lab work was forwarded with request (repeat HCV load, liver function test including ALT/AST) dated 24 weeks after starting therapy to evaluate response to medication. If the patient has a detectable HCV-RNA level at week treatment week 24 then the peginterferon alfa and ribavirin therapy must be discontinued and NO FURTHER TREATMENT WILL BE APPROVED. · PLEASE NOTE: a confirmed `detectable but below limit of quantification' HCV-RNA result should not be considered equivalent to an "undetectable" HCV-RNA result. Please see the Laboratory Test section in the dosage and administration section of Incivek for more information. and · Please see the table entitled "Recommended Treatment Duration" for additional information.

·

The dose that has been prescribed for the patient is consistent with the dosing recommendations listed below and is prescribed by a hepatologist, gastroenterologist, infectious disease specialist, or other specialist experienced in the treatment of Hepatitis C.

If all of the above conditions are met, and the patient has undetectable HCV-RNA levels after 24 weeks of treatment, the request for the peginterferon and ribavirin will be approved for a 20-week duration (or a total of 48 weeks of treatment). If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section L: PA Criteria for reauthorization for treatment experienced patients who received treatment with the three medicine (with Victrelis) regimen for 12-16 weeks of therapy for Hepatitis C · · Appropriate lab work was forwarded with the request (repeat HCV load, liver function test including ALT/AST) dated 8, 12 and 24 weeks after starting therapy to evaluate the initial response to medication. If the patient has a HCV-RNA level greater than 100 IU/ml at week 12 of treatment or a detectable HCVRNA at treatment week 24 the three medicine regimen will be discontinued and no further reauthorizations will be given. · PLEASE NOTE: a confirmed `detectable but below limit of quantification' HCV-RNA result should not be considered equivalent to an "undetectable" HCV-RNA result. Please see the Laboratory Test section in the dosage and administration section of Victerlis for more information. and · Please see the table entitled "Duration of Therapy Using Response-Guided Therapy Guidelines in Patients without cirrhosis" for additional information. The dose that has been prescribed for the patient is consistent with the dosing recommendations listed below and is prescribed by a hepatologist, gastroenterologist or other specialist experienced in the treatment of Hepatitis C.

·

If all of the above conditions are met, and the patient has undetectable HCV-RNA levels after 8 and 12 weeks of treatment, the request will be approved for a 24-week duration (or a total of 36 weeks of treatment) OR if the patient has cirrhosis then the request for all three medications will be approved for a 32 week duration (or a total of 48 weeks). NO FURTHER APPROVALS WILL BE NEEDED. If the patient has detectable levels after 8 weeks of treatment but then a HCV-RNA level of less than 100 IU/mL after 12 weeks of treatment, then the three medicine regimen will be approved for 16 weeks of therapy (or a total of 28 weeks of treatment). If these patients then have an undetectable HCV-RNA level after 24 weeks of treatment then Victrelis will be approved for 8 weeks of therapy (or a total of 36 weeks of treatment) and the peginterferon alfa and ribavirin therapy will be approved for 20 weeks of treatment (or a total of 48 weeks of treatment) OR if the patient has cirrhosis then the request for all three medications will be approved for a 20 week duration (or a total of 48 weeks). NO FURTHER APPROVALS WILL BE NEEDED. If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section M: PA Criteria for authorization for peginterferon alfa-2a for Hepatitis B · The medication is prescribed by a hepatologist, gastroenterologist or other specialist experienced in the treatment of Hepatitis B at an FDA approve or medically accepted dosing. · The patient is an adult (> 18 y/o) · The appropriate lab-work was provided with the request including HBV DNA level by polymerase chain reaction (PCR) assay (result within two months of starting therapy), HBeAg lab results, liver function studies including ALT (result within two months of starting therapy) and if liver function studies are within normal limits before starting therapy a liver biopsy report was submitted, two serial HBsAg results that were completed at least 6 months apart. · Documentation submitted that the patient has compensated liver disease and persistent HBsAg for > 6 months based on 2 serial lab results completed a minimum of 6 months apart. · If the patient is HBeAg positive and ONE of the following apply: A. Documentation was submitted that indicates that the patient has been HBeAg positive for > 3 months unless they have documented icteric ALT flares and ALT (lab result completed within 30 days of request) greater than 2 times normal and/or moderate to severe necroinflammation or significant

fibrosis noted on submitted liver biopsy and HBV DNA > 20,000 IU/mL (completed within 30 days of request). B. Documentation was submitted that indicates that the patient has been HBeAg positive for > 3 months and has ALTs that are persistently normal or high normal (2xULN) and moderate to severe necroinflammation or significant fibrosis noted on submitted liver biopsy and a HBV DNA > 20,000 IU/mL (lab result completed within 30 days of request). · If the patient is HbeAg negative, ONE of the following apply: A. ALT greater than 2 times normal and/or and moderate to severe necroinflammation or significant fibrosis noted on submitted liver biopsy and HBV DNA > 20,000 IU/mL (lab result completed within 30 days of request). B. ALT 1 to > 2xULN and moderate to severe necroinflammation or significant fibrosis noted on submitted on liver biopsy and HBV DNA > 2,000 IU/mL (lab result completed within 30 days of request). If all of the above conditions are met, the request will be approved for a 48-week duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Table 1. Contraindications to Hepatitis-C Therapy · Unstable angina or severe cardiac disease · (CABG, MI, Arrhythmias) in past 12 months. · · Severe COPD · · Uncontrolled autoimmune disorder · · Women who are pregnant and men whose · female partners are pregnant. · · Non-compliance · Inability to self-inject medications · Patients with hemoglobinopathies (e.g. · thalassemia major, sickle-cell anemia)

Severe uncontrolled Psychiatric disease, especially depression with current suicidal risk IVDA Alcohol abuse Inability to use birth control Autoimmune hepatitis Hepatic decompensation(Child-Pugh score >6) in cirrhotic patients or >6 in CHC patients co-infected with HIV before or during treatment Combination with ribavirin if creatinine clearance < 50mL/min

Table 2. Extra-hepatic Signs and Symptoms associated with hepatitis C infection Glomerulonephritis * Joint and muscle aches Porphyria cutanea tarda * Skin rash * Kidney disease Thrombocytopenic purpura * Neuropath Cryoglobulinemia (1-2% of Lichen planus patients Mooren's corneal ulcer Sjögren's syndrome Polyarteritis nodosa Cutaneous Vasculitis Autoantibody formation * Cryoglobulins, Rheumatoid factor, and low complement levels

* Associated with cryoglobulinemia

FDA INDICATIONS: Boceprevir (Victrelis) Chronic Hepatitis C (CHC): Is indicated for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa ribavirin, in adult patients (18 years and older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy. The following points should be considered when initiating Victrelis for treatment for treatment of chronic hepatitis C infection, Victrelis: · Must not be used as monotherapy and should only be used in combination with peginterferon alfa and ribavirin · Efficacy has not been studied in patients who have previously failed therapy with a treatment regimen that included Victrelis or over HCV NS3/4A protease inhibitors · In combination with peginterferon alfa and ribavirin has not been studied in patients documented to be historical null responders (less than a 2log10 HCV-RNA decline by treatment week 12) during prior therapy with peginterferon alfa and ribavirin. The clinical studies included subjects who were poorly

·

interferon responsive. Subjects with less than 0.5log10 HCV-RNA decline in viral load at Treatment Week 4 with peginterferon alfa plus ribavirin alone are predicted to have a null response (less than 2log10 viral load decline at treatment week 12) to peginterferon alfa and ribavirin therapy Poorly interferon responsive patients who were treated with Victrelis in combination with peginterferon alfa and ribavirin have a lover likelihood of achieving a sustained virologic response (SVR), and a higher rate of detection or resistance-associated substitutions upon treatment failure, compared to patient with a greater response to peginterferon alfa and ribavirin.

Telaprevir (Incivek) Chronic Hepatitis C (CHC): Is indicated for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa ribavirin, in adult patients (18 years and older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy. The following points should be considered when initiating Incivek for treatment for treatment of chronic hepatitis C infection, Incivek: · Must not be used as monotherapy and should only be used in combination with peginterferon alfa and ribavirin · Efficacy has not been established in patients who have previously failed therapy with a treatment regimen that included Incivek or over HCV NS3/4A protease inhibitors · A high proportion of previous null responders (particularly those with cirrhosis) did not achieve a Sustained Virologic Response (SVR) and had telaprevir resistance-associated substitutions emerge on treatment with Incivek combination treatment Peginterferon alfa-2a (Pegasys) Chronic Hepatitis C (CHC): Pegasys and Ribavirin are indicated for the treatment of chronic hepatitis C. Pegasys can be used alone or in combination with ribavirin tablets for the treatment of chronic hepatitis C in adult patients (> 18 y/o) with compensated liver disease and who have not been previously treated with interferon alpha. Efficacy has been demonstrated in patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A) and with HIV disease that is clinically stable (e.g. antiretroviral therapy not required or stabilized on antiretroviral therapy) Chronic Hepatitis B: Pegasys is indicated for the treatment of adult patients (> 18 y/o) with HbeAg positive and HbeAg negative chronic hepatitis B who have compensated liver disease and evidence of viral replication and liver inflammation. Peginterferon alfa-2b (PegIntron) Chronic Hepatitis C (CHC): Combination Therapy: PegIntron and ribavirin are indicated for the treatment of chronic hepatitis C in patients 3 years of age and older with compensated liver disease. The following points should be considered when initiating therapy with PegIntron in combination with ribavirin: · These indications are based on achieving undetectable HCV RNA after treatment for 24 or 48 weeks and maintaining a sustained virologic response (SVR) 24 weeks after the last dose. · Patients with the following characteristics are less likely to benefit from retreatment after failing a course of therapy: previous nonresponse, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, and genotype 1 infection · No safety and efficacy data are available for treatment of longer than one year Monotherapy (for patients who are intolerant to ribavirin): PegIntron is indicated for use alone for the treatment of chronic hepatitis C in patients with compensated liver disease previously untreated with interferon alpha and who are at least 18 years of age. The following points should be considered when initiating therapy with PegIntron alone: · Combination therapy with ribavirin is preferred over PegIntron monotherapy unless there contraindications to or significant intolerance of ribavirin. Combination therapy provides substantially better response rates than monotherapy. FDA INDICATIONS: Boceprevir (Victrelis)

Chronic Hepatitis C (CHC): Is indicated for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa ribavirin, in adult patients (18 years and older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy. The following points should be considered when initiating Victrelis for treatment for treatment of chronic hepatitis C infection, Victrelis: · Must not be used as monotherapy and should only be used in combination with peginterferon alfa and ribavirin · Efficacy has not been studied in patients who have previously failed therapy with a treatment regimen that included Victrelis or over HCV NS3/4A protease inhibitors · In combination with peginterferon alfa and ribavirin has not been studied in patients documented to be historical null responders (less than a 2log10 HCV-RNA decline by treatment week 12) during prior therapy with peginterferon alfa and ribavirin. The clinical studies included subjects who were poorly interferon responsive. Subjects with less than 0.5log10 HCV-RNA decline in viral load at Treatment Week 4 with peginterferon alfa plus ribavirin alone are predicted to have a null response (less than 2log10 viral load decline at treatment week 12) to peginterferon alfa and ribavirin therapy · Poorly interferon responsive patients who were treated with Victrelis in combination with peginterferon alfa and ribavirin have a lover likelihood of achieving a sustained virologic response (SVR), and a higher rate of detection or resistance-associated substitutions upon treatment failure, compared to patient with a greater response to peginterferon alfa and ribavirin. Telaprevir (Incivek) Chronic Hepatitis C (CHC): Is indicated for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa ribavirin, in adult patients (18 years and older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy. The following points should be considered when initiating Incivek for treatment for treatment of chronic hepatitis C infection, Incivek: · Must not be used as monotherapy and should only be used in combination with peginterferon alfa and ribavirin · Efficacy has not been established in patients who have previously failed therapy with a treatment regimen that included Incivek or over HCV NS3/4A protease inhibitors · A high proportion of previous null responders (particularly those with cirrhosis) did not achieve a Sustained Virologic Response (SVR) and had telaprevir resistance-associatedsubstitutions emerge on treatment with Incivek combination treatment Peginterferon alfa-2a (Pegasys) Chronic Hepatitis C (CHC): Pegasys and Ribavirin are indicated for the treatment of chronic hepatitis C. Pegasys can be used alone or in combination with ribavirin tablets for the treatment of chronic hepatitis C in adult patients (> 18 y/o) with compensated liver disease and who have not been previously treated with interferon alpha. Efficacy has been demonstrated in patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A) and with HIV disease that is clinically stable (e.g. antiretroviral therapy not required or stabilized on antiretroviral therapy) Chronic Hepatitis B: Pegasys is indicated for the treatment of adult patients (> 18 y/o) with HbeAg positive and HbeAg negative chronic hepatitis B who have compensated liver disease and evidence of viral replication and liver inflammation. Peginterferon alfa-2b (PegIntron) Chronic Hepatitis C (CHC): Combination Therapy: PegIntron and ribavirin are indicated for the treatment of chronic hepatitis C in patients 3 years of age and older with compensated liver disease. The following points should be considered when initiating therapy with PegIntron in combination with ribavirin: · These indications are based on achieving undetectable HCV RNA after treatment for 24 or 48 weeks and maintaining a sustained virologic response (SVR) 24 weeks after the last dose. · Patients with the following characteristics are less likely to benefit from retreatment after failing a course of therapy: previous nonresponse, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, and genotype 1 infection

·

No safety and efficacy data are available for treatment of longer than one year

Monotherapy (for patients who are intolerant to ribavirin): PegIntron is indicated for use alone for the treatment of chronic hepatitis C in patients with compensated liver disease previously untreated with interferon alpha and who are at least 18 years of age. The following points should be considered when initiating therapy with PegIntron alone: · Combination therapy with ribavirin is preferred over PegIntron monotherapy unless there contraindications to or significant intolerance of ribavirin. Combination therapy provides substantially better response rates than monotherapy. DOSAGE AND ADMINISTRATION: Boceprevir (Victrelis) Chronic Hepatitis C (CHC): The dose is 800mg (four 200mg capsules) three times daily (every 7-9 hours) with food [a meal or lack snack]. The following dosing recommendations are based on the response-guided therapy guidelines: · Patients without cirrhosis who are previously untreated or who are previous partial responders or relapsers to interferon and ribavirin therapy o Initiate therapy with peginterferon alfa and ribavirin for 4 weeks o Add Victrelis 800mg orally three times daily to peginterferon alfa and ribavirin regimen after 4 weeks of treatment. Based on the patient's HCV-RNA levels at treatment week 8, 12, and 24. Use the following response-guided therapy guidelines to determine duration of treatment. Duration of Therapy Using Response-Guided Therapy Guidelines in Patients without cirrhosis Assessment (HCV-RNA Results) Recommendation At Treatment At Treatment week 8 week 24 Undetectable Undetectable Complete three-medicine regimen at TW28 Previously 1. Continue all three medicines and Untreated finish through TW36; and then Patients Detectable Undetectable 2. Administer peginterferon alfa and ribavirin and finish through TW48 Undetectable Undetectable Complete three-medicine regimen at Previous Partial TW36 Responders or Relapsers 1. Continue all three medicines and finish through TW36; and then Undetectable 2. Administer peginterferon alfa and Detectable ribavirin and finish through TW48 · Patients with Cirrhosis o Patients with compensated cirrhosis should receive 4 weeks peginterferon alfa and ribavirin followed by 44 weeks of Victrelis 800mg three times a day in combination with peginterferon alfa and ribavirin.

Treatment Futility for all patients · If the patient has HCV-RNA results greater than or equal to 100 IU/ml at TW12, then discontinue three-medicine regimen. If the patient has confirmed, detectable HCV-RNA at TW24, then discontinue three-medicine regimen Laboratory Tests: use of a sensitive real-time reverse-transcription polymerase chain reaction (RT-PCR) assay for monitoring HCV-RNA levels during treatment is recommended. The assay should have a lower limit of HCV-RNA quantification of equal to or less than 25 IU/ml, and a limit of HCV-RNA detection of approximately 10-15 IU/ml. For the purpose of assessing Response-Guided Therapy milestones, a confirmed

`detectable but below limit of quantification' HCV-RNA result should not be considered equivalent to an "undetectable" HCV-RNA result. Telaprevir (Incivek) Chronic Hepatitis C (CHC): The recommendeddose is 750mg (two 375mg tablets) three times daily (every 7-9 hours) with food [not low fat]. · The recommended duration of treatment with Incivek is 12 weeks in combination with peginterferon alfa and ribavirin. HCV-RNA levels should be monitored at weeks 4 and 12 to determine combination treatment druation and assess for treatment futility. Recommeded Treatment Duration Treatment-Naïve and Prior Relapse Patients HCV-RNA Triple Therapy Dual Therapy Incivek + peginterferon alfa peginterferon alfa and ribavirin and ribavirin Undetectable at First 12 weeks Additional 12 weeks Weeks 4 and 12 Detectable (1000 First 12 weeks Additional 36 weeks IU/mL or less) at weeks 4 &/or 12 Prior Partial and Null Responder Patients All Patients First 12 weeks Additional 36 weeks

Total Treatment Duration

24 weeks 48 weeks

48 weeks

Discontinuaton of Dosing: · Patients with inadequate viral responses are unlikely to achieve SVR, and may develop treatmentemergent resistance substitutions Discontinuation of therapy is recommended in all patients with (1) HCV-RNA levels of greater than or equal to 1000 IU/mL at treatment week 4 or 12; or (2) confirmed detectable HCV-RNA levels at treatment week 24 HCV-RNA Week 4 or Week 12: Greater than 1000 IU/mL Week 24: Detectable Action Discontinue Incivek and peginterferon alfa and ribavirin (Incivek treatment complete at 12 weeks) Discontinue peginterferon alfa and ribavirin

Laboratory Tests: In clinical trials, HCV-RNA in plasma was measured using a COBAS TaqMan assay with a lower limit of HCV-RNA quantification of equal to or less than 25 IU/ml, and a limit of HCV-RNA detection of approximately 10 IU/ml. For the purpose of assessing Response-Guided Therapy eligibility at weeks 4 and 12, a confirmed `detectable but below limit of quantification' HCV-RNA result should not be considered equivalent to an "undetectable" HCV-RNA result.

For Peginterferon alfa-2a (Pegasys) Chronic Hepatitis C (CHC), CHC with HIV co-infection or Chronic Hepatitis B Monotherapy: There is no safety and efficacy data on treatment of chronic hepatitis C or hepatitis B for longer than 48 weeks. For patients with hepatitis C, consideration should be given to discontinuing therapy after 12 to 24 weeks of therapy if the patient has failed to demonstrate an early virologic response defined as undetectable HCV RNA or at least a 2 log 10 reduction from baseline in HCV RNA titer by 12 weeks of therapy. CHC Combination Therapy: The recommended dose of Pegasys when used in combination with ribavirin is 180mcg once weekly and is administered up to 24 weeks for genotype 2 and 3 and up to 48 weeks for all other

genotypes depending on 12-16 week clinical response to therapy. The recommended dose of ribavirin depends upon viral genotype. (See Table 5 for ribavirin dosing). CHC with HIV co-infection Combination Therapy: The recommended dose of Pegasys when used in combination with ribavirin is 180mcg once weekly for a total of 48 weeks regardless of genotype. The recommended dose of ribavirin depends upon viral genotype. (See Table 5 for ribavirin dosing). Chronic Hepatitis B Monotherapy: The recommended dose of Pegasys when used as monotherapy for hepatitis B is 180mcg once weekly for a total of 48 weeks. For Peginterferon alfa-2b (PegIntron) CHC Monotherapy: The recommended dose of PegIntron monotherapy is 1 mcg/kg once a week for 48 weeks. (See table 4 for dosing guide) Body weight (kg) Table 4 PegIntron (peginterferon alfa-2b) monotherapy* PegIntron Vial Amount of PegIntron Volume (mL) of Strength PegIntron to (g) to Administer Administer 40 0.4 50 g per 0.5 mL 50 0.5 64 0.4 80 g per 0.5 mL 80 0.5 96 0.4 120 g per 0.5 mL 120 0.5 150 0.5 150 g per 0.5 mL

< 45 46-56 57-72 73-88 89-106 107-136 137-160

CHC Combination Therapy: The recommended dose of PegIntron when used in combination with ribavirin is 1.5 mcg/kg once weekly and is administered up to 24 weeks for genotype 2 and 3 and up to 48 weeks for all other genotypes depending on 12-16 week clinical response to therapy. (See table 5 for dosing PegIntron and ribavirin) Body weight (kg) Table 5 PegIntron (peginterferon alfa-2b) combination therapy PegIntron Vial Amount of PegIntron Volume (mL) of Strength PegIntron to (g) to Administer Administer 50 0.5 50 g per 0.5 mL 64 0.4 80 g per 0.5 mL 80 0.5 96 0.4 120 g per 0.5 mL 120 0.5 120 g per 0.5 mL 120 0.5 120 g per 0.5 mL 150 0.5 150 g per 0.5 mL ** ** ** Ribavirin Daily Dose

< 40 800 mg/day 40-50 800 mg/day 51-60 61-75 800 mg/day 76-80 1000 mg/day 81-85 1200 mg/day 86-105 1200 mg/day >105 1400 mg/day ** For patients weighing greater than 105 kg (greater than 231 pounds), the PegIntron dose of 1.5 mcg/kg/week should be

calculated based on the individual patient weight. Two vials of PegIntron may be necessary to provide the dose.

CHC with HIV co-infection Combination Therapy: The recommended dose of PegIntron when used in combination with ribavirin is 1.5 mcg/kg once weekly. (See table 4 for dosing PegIntron). The recommended dose of ribavirin depends upon viral genotype. (See Table 5 for ribavirin dosing). CHC Combination Therapy for Pediatrics (ages 3 to 17 years old): The recommended dose of PegIntron is 60mcg,/m2/week subcutaneously in combination with ribavirin 15 mg/kg/day divided into 2 doses (or 800 mg/day divided into 2 doses). Patients who reach their 18th birthday while receiving PegIntron/Ribavirin should remain on the pediatric dosing regimen. The treatment duration for patients with genotype 1 is 48 weeks and for patients with genotype 2 or 3 is 24 weeks.

Body Weight (kg) <47 47 ­ 59 60 ­ 73 >73

Ribavirin Daily dose 15 mg/kg/day** 800 mg/day 1000 mg/day 1200 mg/day

** = patients <47 kg can use oral solution however any patient, regardless of body weight, can use the oral solution

DOSE MODIFICATIONS: Table 6.Pegasys Hematological Dose Modifications Guidelines Laboratory Values Pegasys Dose Adjustment Discontinue Pegasys if: ANC < 750/mm3 Reduce to 135 mcg ANC < 500/mm3 treatment should be suspended until ANC values return to more than 1000/mm3 Then reinstate at 90 mcg and monitor ANC. Platelet <50,000/mm3 Reduce to 90 mcg Platelet count < 25,000/mm3 Table 7. Pegasys Renal and Hepatic Dose Modifications Guidelines Condition Pegasys Dose Adjustment End stage renal disease on dialysis. Reduce to 135 mcg CHC with progressive ALT increases above baseline values. Chronic Hepatitis B with ALT >5 x ULN Persistent severe Hepatitis B flares with ALT > 10x ULN Reduce to 135 mcg Reduce to 135 mcg or temporarily discontinue treatment until flare subsides. Consider discontinue treatment

Table 8. Ribavirin Dose Modifications Guidelines when used with Pegasys Laboratory Values Reduce Only Ribavirin Dose Discontinue Ribavirin if: to 600 mg/day* if: Hemoglobin in patients with Hemoglobin < 10 g/dL Hemoglobin < 8.5 g/dL no cardiac disease Hemoglobin in patients with 2 g/dL decrease in <12 g/dL despite 4 weeks at reduced history of stable cardiac hemoglobin during any 4 dose disease week treatment period *if dose of Ribavirin has been withheld may attempt to restart at 600mg/day and further increase to a maximum of 800mg/day upon

physician's judgement.

General Dose Modifications for Pegasys (peginterferon alfa-2a): may be required for moderate to severe adverse reactions. Initial dose reduction to 135 mcg. In some cases dose reduction to 90 mcg may be needed. Examples: moderate depression reduce dose to 135 mcg and provide psychiatric consultation, if stable continue reduced dose or if improves consider returning to 180 mcg. If no improvement reduce to 90 mcg. Severe depression discontinue Pegasys permanently. Table 9. PegIntron Hematological Dose Modifications Guidelines Laboratory Values PegIntron

Ribavirin

Adults

Hgb < 10 g/dl For patients with cardiac disease reduce by 50%

Pediatrics

See footnote* 1st reduction to 40mcg/m2/week 2nd reduction to 20mcg/m2/week

Adults

Decrease by 200 mg/day

Pediatrics

1st reduction to 12 mg/kg/day 2nd reduction to 8 mg/kg/day

WBC < 1.5 x 109/L Neutrophils < 0.75 x 109/L Platelets < 80 x 109/L (Adults) Platelets < 70 x 109/L (Pediatrics)

Reduce by 50%

No Dose Change

No Dose Change

Hgb < 8.5 g/dL WBC < 1.0 x 109/L Permanently Permanently Permanently Permanently Neutrophils < 0.50 x 109/L Discontinue Discontinue Discontinue Discontinue 9 Platelets < 50 x 10 /L Creatinine > 2 mg/dL (Pediatrics) *For adult patients with a history of stable cardiac disease receiving PegIntron in combination with ribavirin, the PegIntron dose should

be reduced by half and the ribavirin dose by 200 mg/day if a > 2 g/dL decrease in hemoglobin is observered in any 4-week period. Both PegIntron and ribavirin should be permanently discontinued if patients have hemoglobin levels < 12 g/dL after this ribavirin dose reduction. Pediatric patients who have pre-existing cardiac conditions and experience a hemoglobin decrease > 2 g/dL any 4 week period during treatment should have weekly evaluations and hematology testing.

Table 10. Comparison of Scoring System for a Liver Biopsy (Histological Stage) Stage IASL Batts-Ludwig Metavir Ishak No Fibrosis No Fibrosis No Fibrosis No Fibrosis 0 Mild Fibrosis Fibrous portal expansion Periportal portal Fibrous expansion of 1

expansion some portal areas with or without short fibrous septa Fibrous expansion of most portal areas with or without short fibrous septa Fibrous expansion of most portal areas with occasional portal to portal bridging Fibrous expansion of most portal areas with marked bridging Marked bridging with occasional nodules Cirrhosis

2

Moderate Fibrosis

Rate bridges or septae

Periportal septae 1

3

Severe Fibrosis

Numerous bridges or septae

Porto-central septae

4 5 6

Cirrhosis

Cirrhosis

Cirrhosis

IASL = International Association for the Study of the liver

REFERENCES: 1. Yee HS. Currie SL. Darling JM. Et al. Management and treatment of hepatitis C viral infection: Recommendations from the Department of Veterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program Office. Practice Guidelines. American Journal of Gastroenterology. 2006;101:2360-2378. 2. National Institutes of Health. Chronic Hepatitis C: Current Disease Management. National Institute of Diabetes and Digestive and Kidney Diseases. U.S. Department of Health and Human Services. Available at: http://digestive.niddk.nih.gov/ddiseases/pubs/chronichepc/chronichepc.pdf. Last updated November 2006. Accessed May 9, 2007. 3. Ghany MG, Strader DB, Thomas DL, Seef LB. Diagnosis, management and treatment of Hepatitis C: An Update. American Association for the Study of Liver Diseases Practice Guideline. Hepatology. 2008; 49(4): 1335-74. 4. Lok ASF. McMahon BJ. Chronic Hepatitis B. American Association for the Study of Liver Diseases Practice Guidelines. Hepatology. 2007;45(2):507-539. 5. NIH Consensus Development Program: National Institutes Health Consensus Conference Statement June 10-12, 2002. Management of Hepatitis C. guidelines. Available from URL: http://consensus.nih.gov/cons/116/Hepc091202.pdf. 6. Department of Veterans Affairs. A Supplement to Federal Practitioner. VA recommendations version 5.0. Patients with chronic Hepatitis C. 2003;20(5):1-33. 7. Alberti A. Clumeck N. Collins S. et al. Short statement of the first European Consensus Conference on the treatment of chronic Hepatitis C and B in HIV Co-infected patients. March 1-2, 2005. Paris, France. Published in the Journal of Hepatology in May 2005. Available at http://www.hivandhepatits.com. Accessed May 14, 2007. 8. Soriano V. Highlights of the 2nd International Workshop on HIV and Hepatitis Co-infection. January 12-14, 2006. Amsterdam, The Netherlands. Medscape HIV/AIDS. 2006;12(1). Available at http://www.medscape.com. Accessed May 14, 2007. 9. Soriano V. Puoti M. Sulkowski M. et al. Care of patients with Hepatitis C and HIV co-infection. AIDS. 2004;18:1-12. 10. Swan T. Raymond D. Sherman KE. Et al. Hepatitis C Virus and HIV/HCV Co-infection. A critical review of research and treatment. Treatment Action Group (TAG). July 2004. Available at: http://www.aidsinfonyc.org/tag/coinf/hcv2004. Accessed May 14, 2007. 11. Department of Veterans Affairs. Hepatitis C Resource Centers. Management and treatment of Hepatitis C virus infection in HIV-infected adults: Recommendation from the Veterans Affairs Hepatitis C Resource Center Program and National Hepatitis C Program Office. American Journal of Gastroenterology. 2005;100(10):2338-2354. Also available online at: http://www.hepatitis.va.gov/pdf/va01-pr/prtop-06/2005_coinf_recs.pdf. Accessed May 14, 2007. 12. Pegasys and Copegus package information. Roche Pharmaceuticals. June 2010. 13. PegIntron and Rebetrol package information. Schering Corporation. June 2011. 14. Victrelis prescribing information. Schering Corporation. May 2011 15. Incivek prescribing information. Vertex Pharmaceuticals Inc. May 2011

Revision/Review Date: 6/2011

Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgement, the requested item is medical ry

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA FOR HYALURONIC ACID DERIVATIVES EUFLEXXA®(hyaluronate sodium): 20 mg/2ml syringe HYALGAN®(hyaluronate sodium): 20mg/2ml syringe SYNVISC®(hylan G-F 20): 16mg/2ml syringe SYNVISC® One (hylan G-F 20): 48mg/6ml syringe SUPARTZ®(hyaluronate sodium): 25mg/2.5ml syringe ORTHOVISC®(hyaluronate sodium): 30mg/2ml syringe ANY NEWLY MARKETED hyaluronic acid deriviative PA CRITERIA FOR INITIAL APPROVAL: · There is a diagnosis of mild to moderate Osteoarthritis (OA)/Degenerative joint disease (DJD) of the knee · There is documentation that the patient recently (over the past 4 months) has had adequate trials on simple analgesics (acetaminophen containing products or topical capsaicin cream) & NSAIDS (including 2 different prescription strength NSAIDS) on a continuous basis for 3 months without success or has a medical reason (intolerance, hypersensitivity, contraindication, etc) for not being able to utilize simple analgesic products and NSAIDS · The patient has recently (within past 2 months) tried steroid injections and aspiration for effusion without success, per affected knee or has a medical reason for not being able to utilize steroid injections · If the medication request is for Hyalgan, Synvisc, Synvisc-One, Supartz, Orthovisc or any other newly marketed hyaluronic acid derivative (HAD), the patient has a documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not taking Euflexxa to treat their medical condition. If all of the above conditions are met, the request will be approved for a 3 to 5-week duration (based the FDA labeled dose of the HAD requested); if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR RE-AUTHORIZATION: · At least 6 months have elapsed since the previous course of HAD therapy for the treated knee(s). · Documentation was submitted that the patient had an objective response to the treated knee (s) that lasted for > 6 months to previous HAD therapy, as documented by at least ONE of the following: · Decreased joint pain or stiffness · Improvement in standard indices such as WOMAC osteoarthritis index or Lequesne's functional index · Improved knee range of motion · Decrease in midpatellar knee circumference in millimeters · Synovial effusion absent or volume decreased · Decrease in the need for intra-articular agents (anesthetics, corticosteroids), knee aspiration, analgesics or anti-inflammatory medications for the management of the treated knee(s) following the previous course of HAD that is consistent with pharmacy claims data. · Documentation was submitted that the patient has a return of symptoms of osteoarthritis. If all of the above conditions are met, the request will be approved for a 3 to 5-week duration (based the FDA labeled dose of the HAD requested); if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested.

FDA INDICATION: Euflexxa, Hyalgan, Synvisc, Synvisc-One, Supartz and Orthovisc are all indicated for the treatment of pain in osteoarthritis (OA) of the knee in patients who have failed to respond to conservative non-pharmacologic therapy and simple analgesics. DOSAGE AND ADMINISTRATION: Euflexxa: Give a dose of 20 mg in 2 mL at weekly intervals for 3 weeks for a total of 3 injections. Hyalgan: Give a dose of 20 mg in 2 mL at weekly intervals for 5 weeks for a total of 5 injections. Synvisc: Give a dose of 16 mg in 2 mL at weekly intervals for 3 weeks for a total of 3 injections. Synvisc One: Given as one intra-articular injection. Supartz: Give a dose of 25 mg in 2.5 mL at weekly intervals for 5 weeks for a total of 5 injections. Orthovisc: Give a dose of 30 mg in 2 mL at weekly intervals for 3 or 4 weeks for a total of 3 to 4 injections. **All hyaluronic acid derivatives are injected intra-articularly into the affected knee. Remove joint effusion if present before injecting any hyaluronic acid derivative. Injection of a local anesthetic (eg, lidocaine) subcutaneously prior to administration can be performed.**

REFERENCES: 1. Altman RD. Hochberg MC. Moskowitz RW. Et al Recommendations for the Medical Management of Osteoarthritis of the Hip and Knee ­ American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis & Rheumatism. 2000; 43:1905-1915. 2. Kotz R, Kolarz G. Intra-articular Hyaluronic Acid: Duration of Effect and Results of Repeated Treatment Cycles. Amer Journ of Orthop. 1999; 28(11 Suppl): 5-7. 3. American Academy of Orthopaedic Surgeons. [resource of the World Wide Web]. www.aos.org. Accessed 2002 October 23. 4. Anonymous. Managing Osteoarthritis: New ACR Guidelines. Women's Health. 2001; 4:97-99. 5. Evanich, J. et al. Efficacy of Intraaticular Hyaluronic Acid injections in knee osteoarthritis. Clinical Othopaedics and related research. 2001; 390:173-181 6. Raynauld J-P et al. Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee. A randomized, double-blind, placebo- controlled trial. Arthritis Rheum 2003 Feb;48:370-7 7. Leopold SS et al. Corticosteroid compared with hyaluronic acid injections for the treatment of osteoarthritis of the knee: A prospective, randmized trial. J Bone Joint Surg Am 2003 Jul; 85:1197-203. 8. Hochberg MC. Altman RD. Brandt KD. Et al. American College of Rheumatology. Guidelines for the medical management of osteoarthritis. Arthritis & Rheumatism. 1995;38(11):1541-1546. 9. American Academy of Orthopaedic Surgeons step approach to treating adult patients with osteoarthritis of the Knee.Phase I,II. Version 1.0. 2003. 10. Scali JJ. Intra-articular hyaluronic acid in the treatment of osteoarthritis of the knee: a long term study. European journal of Rheumatology and Inflammation. 1995;15(1):1-6. 11. Kirchner M. Marshall K. A double-blind randomized controlled trial comparing alternate forms of high molecular weight hyaluronan for the treatment of osteoarthritis of the knee. OsteoArthritis and Cartilage.2005;1-9. 12. Hanson EC. Sodium hyaluronate-Application in a community practice. A supplement to the American Jounal of Orthopedics.November 1999.pp11-12. 13. Felson DT. Anderson JJ. Hyaluronate sodium injections for osteoarthritis: hope, hype and hard truths. Archives of Internal Medicine. 2002;162(3):245-247. 14. Brandt KD. Block JA. Michalski JP. Et al. Efficacy and safety of intraarticular sodium hyaluronate in knee osteoarthritis. Clinical Orthopaedics and Related Research. 2001;1(385):130-143. 15. Petrella RJ. DiSelvestro MD. Hildebrand C. Effects of hyaluronate sodium on pain and physical functioning in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled clinical trial. Archives of Internal Medicine. 2002;162(3):292-298. 16. Day R. Brooks P. Conaghan PG. Et al. A double-blind, randomized, multicenter, parallel group study of the effectiveness and tolerance of intraarticular hyaluronan in osteoarthritis of the knee. The Journal of Rheumatology.2004;31:775-782. 17. Niethard FU. Pathogenesis of osteoarthritis--Approaches to specific therapy. A supplement to the American Journal of Orthopedics. Novemer 1999.pp8-10. 18. Medical Policy Synvisc, Supartz, Hyalgan: Blue Cross California 19. Aetna Coverage Policy Bulletins. Subject Sodium hyaluronate and Hylan G-F20.4/26/02 20. Schwenk TL. Journal Watch. Hyaluronic acid is minimally effective in osteoarthritis. 1/23/04. 21. Brett AS. Journal Watch. Intra-articulr hyaluronic acid vs. steroids for knee osteoarthritis. 7/29/03. 22. Rapp SM. Hyaluronic acid meta-analysis results, methodology questioned. Orthopedics Today. 2004. 23. Brett AS. Journal Watch. Repeated steroid injections for knee osteoarthritis: beneficial or harmful? 3/21/03. 24. Euflexxa® product information. 2/06. 25. Hyalgan® product information. 1/09. 26. Orthovisc® product information 6/05. 27. Synvisc® product information 12/06. 28. Synvisc® One product information 3/09 29. Supartz® product information 1/2007

Revision/Review Date: 8/2011 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgement, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA Infergen® (interferon alfacon-1): 15 mcg/0.5 ml vial, 9 mcg/0.3 ml vial Ribavirin: 200mg tablet Section A: PA Criteria for authorization of combination treatment with Infergen and ribavirin in patients who have failed treatment with either a pegylated interferon or standard interferon with or without ribavirin. · · · · The appropriate lab-work was provided with request including HCV RNA viral load (result within one month of starting therapy), liver function studies (result within one month of starting therapy) and genotype, if liver function studies are within normal limits before starting therapy a liver biopsy report was submitted. The patient's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are abnormal or the patient has a liver biopsy result (greater than Ishak stage 0-2 or Metavir, IASL, and Batts-Ludwig stage 0-1-see table 3) or another noninvasive procedure that shows the patients has advanced to severe fibrosis. The patient does not have a history of kidney, heart, or other solid-organ transplant (excluding liver transplant). The patient has a documented trial and failure (non-responder or relapsed) of at least two of the listed therapeutic options, with or without Ribavirin, OR has a documented medical reason for not being able to tolerate any of the listed therapeutic options. The therapeutic options include: pegylated interferons (Peg Intron® or Pegasys®) or non-pegylated interferon (Intron A®). The patient does not have a medical condition or other risk factors (see table 1) in which treatment is contraindicated If the patient has a history of a co-morbid condition that could be a contraindication, the prescribing physician submitted adequate documentation that indicates the condition is either clinically resolved or is being appropriately medically managed and stable. The dose that has been prescribed for the patient is consistent with the FDA recommended dosing.

· · ·

If all of the above conditions are met, and the patient has Genotype 1, 4 or 6 or the patient has Genotype 2 or 3 and is co-infected with HIV, the request will be approved with 16-week duration; if the patient has Genotype 2 or 3 and not co-infected with HIV, the request will be approved for the 24 weeks of therapy, if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section B: PA Criteria for authorization of monotherapy with Infergen for patients who failed previous treatment with pegylated interferon or standard interferon · · · · · · · · The patient has a documented trial and failure (non-responder or relapsed) of at least two of the listed therapeutic options as monotherapy OR has a documented medical reason for not being able to tolerate any of the listed therapeutic options. The therapeutic options include: pegylated interferons (Peg Intron® or Pegasys®) or non-pegylated interferon (Intron A®). The patient has a documented medical reason (i.e. ESRD, etc.) for not receiving Ribavirin. The appropriate lab-work was provided with request including HCV RNA viral load (result within one month of starting therapy), liver function studies (result within one month of starting therapy) and genotype, if liver function studies are within normal limits before starting therapy a liver biopsy report was submitted. The patient's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are abnormal or the patient has a liver biopsy result (greater than Ishak stage 0-2 or Metavir, IASL, and Batts-Ludwig stage 0-1-see table 3) or another noninvasive procedure that shows the patients has advanced to severe fibrosis. The provider submitted documentation that the patients had clinical signs or symptoms or extra-hepatic (cryoglobulinemia, glomerulonephritis ­ see table 2) symptoms that improved while on interferon therapy or worsened while off therapy despite not eradicating the Hepatitis C virus. The patient does not have a medical condition or other risk factors (see table 1) in which treatment is contraindicated If the patient has a history of a co-morbid condition that could be a contraindication, the prescribing physician submitted adequate documentation that indicates the condition is either clinically resolved or is being appropriately medically managed and stable. The dose that has been prescribed for the patient is consistent with the FDA recommended dosing.

If all of the above conditions are met, and the patient has Genotype 1, 4 or 6 or the patient has Genotype 2 or 3 and is co-infected with HIV, the request will be approved with 16-week duration; if the patient has Genotype 2 or 3 and not co-infected with HIV, the request will be approved for the 24 weeks of therapy, if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section C: PA Criteria for re-authorization for patients who received treatment for 12-16 weeks of therapy · Appropriate lab work was forwarded with request (repeat HCV load, liver function test including ALT/AST) dated 12 weeks after starting therapy to evaluate initial response to medication.

· · · ·

The patient has responded to treatment (complete eradication of HCV RNA levels or > 2 log decrease in HCV RNA viral load after receiving 12-16 weeks of therapy) and the dose that has been prescribed for the patient is consistent with the FDA dosing recommendations listed below. The patient does not have a medical condition or other risk factors (see table 1) in which treatment is contraindicated If the patient has a history of a co-morbid condition that could be a contraindication, the prescribing physician submitted adequate documentation that indicates the condition is either clinically resolved or is being appropriately medically managed and stable. The dose that has been prescribed for the patient is consistent with the FDA recommended dosing.

If all of the above conditions are met, the request will be approved for up to a 48-week total duration for Genotypes 1 and other genotypes except for 2 and 3, if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. · · · · · · Table 1. Contraindications to Hepatitis-C Therapy Unstable angina or severe cardiac disease · Severe uncontrolled Psychiatric disease, (CABG, MI, Arrhythmias) in past 12 especially depression with current suicidal risk months. · IVDA Severe COPD Uncontrolled autoimmune disorder · Alcohol abuse · Inability to use birth control Pregnancy Non-compliance Inability to self-inject medications

Table 2. Extra-hepatic Signs Symptoms associated with hepatitis C infection Glomerulonephritis * Joint and muscle aches Porphyria cutanea tarda * Skin rash * Kidney disease Thrombocytopenic purpura * Neuropath Cryoglobulinemia (1-2% of Lichen planus patients Mooren's corneal ulcer Sjögren's syndrome Polyarteritis nodosa Cutaneous Vasculitis Autoantibody formation * Cryoglobulins, Rheumatoid factor, and low complement levels

* Associated with cryoglobulinemia

Stage 0 1

Table 3. Comparison of Scoring System for a Liver Biopsy (Histological Stage) IASL Batts-Ludwig Metavir Ishak

No Fibrosis Mild Fibrosis No Fibrosis Fibrous portal expansion No Fibrosis Periportal portal expansion No Fibrosis Fibrous expansion of some portal areas with or without short fibrous septa Fibrous expansion of most portal areas with or without short fibrous septa Fibrous expansion of most portal areas with occasional portal to portal bridging Fibrous expansion of most portal areas with marked bridging Marked bridging with occasional nodules Cirrhosis

2

Moderate Fibrosis

Rate bridges or septae

Periportal septae 1

3

Severe Fibrosis

Numerous bridges or septae

Porto-central septae

4 5 6

Cirrhosis

Cirrhosis

Cirrhosis

IASL = International Association for the Study of the liver

FDA INDICATION: Infergen is indicated for the treatment of chronic hepatitis C viral (HVC) infection in patients 18 years of age or older with compensated liver disease. The following points should be considered when initiating treatment with Infergen:

o o o

o

Use of monotherapy with an interferon such as Infergen for the treatment of hepatitis C is not recommended unless a patient is unable to take ribavirin. The safety and efficacy of the combination of Infergen/ribavirin in treatment-naïve patients or in patients co-infected with HBV or HIV-1 have not been evaluated Patients with the following any or a combination of the following characteristics are less likely to benefit from retreatment with combination therapy o Response of <1 log10 drop HCV RNA on previous treatment o Genotype 1 o High viral load (> 850,000 IU/ml) o African-American race o Presence of cirrhosis No safety and efficacy data are available for treatment of longer than one year Table 4. Dosing of Ribavirin when combined with Infergen Ribavirin combination therapy Body weight (kg) Amount of Ribavirin (mg) to administer BW < 75 kg 1000 mg/day for 48 weeks BW > 75 kg 1200 mg/day for 48 weeks All 800 mg/day for 24 weeks

Genotypes Genotype 1, 4 Genotype 1, 4 Genotype 2, 3

DOSAGE AND ADMINISTRATION: The FDA recommended dosing of Infergen: o As Monotherapy: For the treatment of chronic HCV infection the dose is 9 mcg three times a week (TIW) administered as a SC single injection for 24 weeks. At least 48 hours should elapse between doses of Infergen. Patients who tolerated previous interferon therapy and did not respond or relapsed following its discontinuation may be subsequently treated with 15 mcg of Infergen TIW administered as a SC single injection for up to 48 weeks. o As Combination Therapy: The recommended dose is 15 mcg daily administered as a single SQ injection in combination with weight-based ribavirin at 1,000mg-1,200mg (<75kg and >75kg) orally in two divided doses for up to 48 weeks. DOSE REDUCTION: For patients who experience a severe adverse reaction during treatment the Infergen and/or ribavirin should be discontinued or the dose modified until the adverse event ends or decreases in severity. If persistent or recurrent serious adverse events develop despite adequate dosage adjustments then treatment must be discontinued. Dose Modifications on Monotherapy: Dose reduction to 7.5 mcg may be necessary following a serious adverse reaction Dose Modifications on Combination: Therapy: A stepwise dose reduction from 15 mcg to 9mcg and from 9 mcg to 6 mcg may be necessary for serious adverse reactions.

REFERENCES: 1. Centers for Disease Control and Prevention, Workowski KA. Berman SM. Hepatitis C. Sexually transmitted diseases treatment guidelines 2006. MMR Morbidity Mortality Weekly Report. 2003 Aug 4;55(RR-11):76-78. Available at http://www.guideline.gov/summary/summary.aspx?view_id=1&doc_id=9685. Accessed 11/7/06. 2. Rigsby M. Burgess J. Davey V. et al. VA treatment recommendations (version 5.0). Patients with chronic hepatitis C. Federal Practitioner. 2003;20(suppl 5):1-33. 3. Ghany MG, Strader DB, Thomas DL, Seef LB. Diagnosis, management and treatment of Hepatitis C: An Update. American Association for the Study of Liver Diseases Practice Guideline. Hepatology. 2008; 49(4): 1335-74. 4. Centers of Excellence in Hepatitis C Research and Education, http://www.va.gov/hepatitisc (June 20, 2003) 5. National Digestive Diseases Information Clearinghouse. A service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Chronic Hepatitis C: Current Disease Management. Available from www.niddk.nih.gov (February 2003) 6. NIH Consensus Development Program. Management of Hepatitis C:2002. Available from URL: http://consensus.nih.gov/cons/116/Hepc091202.pdf. 7. Fattovich G. Zagni I. Minola E. et al. A randomized trial of consensus interferon in combination with ribavirin as initial treatment for chronic hepatitis C. Journal of Hepatology. 2003;39:843-849. 8. Infergen® package information. Valeant Pharmaceuticals North America 7/2010. 9. Bacon BR, Shiffman ML, Mendes F, et al. Retreating Chronic Hepatitis C with Daily Interferon Alfacon-1/Ribavirin After Nonresponse to Pegylated Interferon/Ribavirin: DIRECT Results. Hepatology 2009; 49.

Revision/Review Date: 1/2011 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION PROTOCOL FOR INJECTABLE BISPHOSPHONATES & SKELETAL-RELATED EVENTS MEDICATIONS Preferred Agent Pamidronate disodium (Aredia®): 3mg/ml, 6 mg/ml, 9 mg/ml liquid in10 ml vials, 30 mg, 90 mg vials Non-preferred Agents (requires prior authorization) Zoledronic Acid (Zometa ®): 4 mg/5 ml vial Denosumab (Xgeva®): 120mg/1.7ml

PREFERRED STATUS: Generic Pamidronate Preferred

Initial Approval: The request for the medication is for an Food and Drug Administration (FDA) approved indication, or is used for a medical condition that is supported by the medical compendium (Micromedex, American Hospital Formulary Service (AHFS), United States Pharmacopeia Drug Information for the Healthcare Professional (USP DI) , Drug Package Insert) as defined in the Social Security Act 1927 or per the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), or the National Institutes of Health (NIH) Consensus Panel standard of care guidelines. If the medication request is for Denosumab (Xgeva), Zolederonic Acid (Zometa), or any other brand only available injectable bisphosphonate or agent indicated for the prevention or treatment of skeletalrelated events in patients with bone metastases for treating a medical condition other than postmenopausal osteoporosis, the patient has a documented (consistent with pharmacy claims data) treatment failure after receiving an adequate trial (including dates, 3 months or more of therapy) of generic Pamidronate (Aredia) or has a documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not utilizing these agents to manage their medical condition. Prescribed dosing of medication is within FDA approved indications or is supported by the medical compendium as defined by the Social Security Act or per the NCCN, ASCO, or NIH standard of care guidelines.

If all of the above conditions are met, the request will be approved for 3 months or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per the NCCN, ASCO, NOF or NIH standard of care guidelines; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Reauthorization of Medication: The prescribing physician has provided documentation as to the clinical benefits of the medication supporting continued treatment, OR the medication is being continued in accordance with the recommended time as defined by FDA drug package insert, and/or per recommendations of the medical compendium as described above, and/or per the NCCN, ASCO, or NIH standard of care guidelines. Prescribed dosing of medication is within FDA approved indications and/or supported by the medical compendium as defined by the Social Security Act and/or per the NCCN, ASCO, or NIH standard of care guidelines.

If all of the above conditions are met, the request will be approved for up to 3 months or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per the NCCN, ASCO, or NIH standard of care guidelines; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested.

FDA APPROVED INDICATIONS AND DOSING: Pamidronate disodium (Aredia): Hypercalcemia of Malignancy ­ in conjunction with adequate hydration, is indicated for the treatment of moderate or severe hypercalcemia associated with malignancy, with or without bone metastases. o For patients with moderate hypercalcemia (corrected serum calcium of approximately 12-13.5 mg/dL) the recommended dose is 60 to 90 mg given as a single dose, intravenous infusion over 2 ­ 24 hours. Longer infusions (i.e. > 2hours) may reduce the risk for renal toxicity, particularly in patients with preexisting renal insufficiency. o For patients with severe hypercalcemia (corrected serum calcium >13.5 mg/dL) the recommended dose is 90 mg given as a single dose intravenous infusion over 2 ­ 24 hours. Longer infusions (i.e. > 2hours) may reduce the risk for renal toxicity, particularly in patients with preexisting renal insufficiency. o A limited number of patients have received more than one treatment for hypercalcemia. Retreatment with Aredia, in patients who show complete or partial response initially, may be carried out if serum calcium does not return to normal or remain normal after initial treatment. It is recommended that a minimum of 7 days elapse before retreatment, to allow for full response to the initial dose. The dose and manner of retreatment is identical to that of the initial treatment. Paget's Disease ­ is indicated for the treatment of patients with moderate to severe Paget's disease of bone. The effectiveness of Aredia was demonstrated primarily in patients with serum alkaline phosphatase > 3 times the upper limit of normal. o The recommended dose is 30 mg daily, administered as a 4 hour infusion on 3 consecutive days for a total dose of 90mg. A limited number of patients have received more than one treatment in clinical trials. When clinically indicated, patients should be retreated at the dose of initial therapy. Osteolytic Bone Metastases of Breast Cancer and Osteolytic Lesions of Multiple Myeloma ­ in conjunction with standard antineoplastic therapy is indicated for the treatment of osteolytic bone metastases of breast cancer and osteolytic lesions of multiple myeloma. o The recommended dose for patients with osteolytic bone lesions of multiple myeloma is 90 mg administered as a 4 hour infusion given on a monthly basis. Limited information is available on the use of Aredia in patients with a serum creatinine > 3.0g/dL. o The recommended dose for patients with osteolytic bone metastases of bone cancer is 90 mg administered over a 2 hour infusion given every 3 -4 weeks.

Denosumab (Xgeva): Bone Metastasis from Solid Tumors ­ is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors o The recommended dose is 120 mg administered as a subcutaneous injection every 4 weeks in the upper arm, upper thigh, or abdomen.

Zoledronic Acid (Zometa): Hypercalcemia of Malignancy ­ is indicated for the treatment of hypercalcemia of malignancy defined as an albumin-corrected calcium (cCa) of >12 mg/dl {3.0 mmol/L] using the formula: cCa in mg/dl = Ca in mg/dl + 0.8 (mid-rang of measure albumin in mg/dl). o The maximum recommended dose is 4 mg. The 4 mg dose must be given as a single-dose intravenous infusion over no less than 15 minutes. Patients who receive Zometa should have their serum creatinine assessed prior to each treatment. Dose adjustments are not necessary in treating patients with hypercalcemia of malignancy presenting with mild-to-moderate renal impairment prior to initiation of therapy (serum creatinine < 4.5mg/dL). Multiple Myeloma and Bone Metastases of Solid Tumor ­ is indicated for the treatment of patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy.

o

The recommended dose for patients with a CrCl > 60 mL/min is 4 mg infused over no less than 15 minutes every 3 -4 weeks. The optimal duration of therapy is not known. Patients should also be administered an oral calcium supplement of 500mg and a multiple vitamin containing 400 IU of vitamin D daily. Upon initiation of treatment the recommended dose for patients with reduced renal function should be: Reduced Doses for Patients with a Baseline CrCl < 60ml/min Baseline Creatinine Clearance (mL/min) Recommended Dose of Zometa > 60 4 mg 50 ­ 60 3.5 mg 40 ­ 49 3.3 mg 30 ­ 39 3 mg

Definition of Hypercalcemia Normal serum calcium (Ca) level is 8-10 mg/dL (2-2.5 mmol/L) Mild: Total Ca 10.5-11.9 mg/dL (2.5-3mmol/L) Moderate: Total Ca 12-13.9 mg/dL (3-3.5 mmol/L) Hypercalcemia is defined as a serum calcium level greater than 10.5 mg/dL (>2.5 mmol/L) Hypercalcemic crisis: Total Ca 14-16 mg/dL (3.5-4 mmol/L) For every 1 g/dL (1 g/L) drop in serum albumin below 4 g/dL (40 g/L), measured serum calcium decreases by 0.8 mg/dL (0.02 mmol/L). Therefore, if albumin level < 4 g/dL (40 g/L) need to correct calcium based on the following formulas: Corrected Ca = (4g/dL - (plasma albumin) X 0.8 + serum calcium, g/dL) or Corrected Ca = serum calcium, mmol/L = {(40-[plasma albumin]) X 0.02}

References:

1. Murphy KC. Nakashima L. Khoo K. BCCA Protocol Summary Guidelines for the diagnosis and management of malignancy related hypercalcemia. BC Cancer Agency: Care and Research web site: http://www.bccancer.bc.ca. Accessed on March 2, 2005 Novartis Pharmaceutical Corporation. Zometa (zoledronic acid) injection prescribing information. Updated 2/2011. Novartis Pharmaceutical Corporatin. Aredia(pamidronate disodium) injection prescribing information. Updated 2/2006. Xgeva Prescribing Information. Amgen November 2010 National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Breast Cancer. Prostate Cancer. Multiple Myeloma Available at http://www.nccn.org/patients/patient_gls/_englis/_prostate/4_treatment.asp Berenson, JR, Hillner BE, Kyle RA, et al. American society of clinical oncology clinical practice guidelines: the role of bisphosphonate in multiple myeloma. J Clin Oncol 2002; 20(17): 3719-36. Coleman RE. Efficacy of zoledronic acid and pamidronate in breast cancer patients: a comparative analysis of randomized phase III trials. Am J of Clin Oncol 2002; 25(suppl 1): S25-S31. Widler L, Jaeggi KA, Glatt M et al. Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa). J of Med Chem 2002; 45(17): 3721-38 (Abstract). Rosen LS, Gordon D, Kaminski M, et al. Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer. 2003; 98:1735-44. Rosen LS, Gordon DH, Dugan W Jr, et al. Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion. Cancer 2004; 100:36-43. Major P, Lortholary A, Hon J, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol 2001; 19(2): 558-67. Clinical Policy Bulletins. Pamidronate (Aredia). http://www.aetna.com/cpb/data/CPBA0672.html . Accessed on March 14, 2005. Magnuson WG. Daniels CE. Calis KA. Et al. National Institute of Health. Pharmacy Update. Zoledronic Acid for Injection. Special Issue. March/April 2002. Kellinsalmi M. Monkkonen H. Monkkonen J. et al. In vitro comparison of Clodronate, Pamidronate and Zoledronic Acid effects on rate osteoclasts and human stem cell-derived osteoblasts. Basic & Clinical Pharmacology & Toxicology. 2005;97:382-391. Brown JE. Neville-Webbe H. Coleman RE. The role of bisphosphonates in breast and prostate cancers. Endocrine-Related Cancer. 2004;11: 207-224. Reed SD. Radeva JI. Glendenning A. et al. Economic evaluation of zoledronic acid versus pamidronate for the prevention of skeletal-related events in metastatic breast cancer and multiple myeloma. American Journal of Clinical Oncology. 2005;28 (1):8-16. Parker, CC. The role of bisphosphonates in the treatment of prostate cancer. BJU International.2005;95:935-938.

2. 3. 4. 5. 6. 7. 8. 9.

10. 11. 12. 13. 14.

15. 16.

17.

18. Coldwell, B. Head LR. White D. et al. Guidelines for the use of zoledronic acid for the treatment of tumor-induced hypercalcemia QEII health sciences centre/cancer care Nova Scotia. Oncology Subcommittee. 2001 19. Oneschuk D. et al. Palliative.org Regional palliative care program in Edmonton Alberta. Clinical Information on Hypercalcemia of Malignancy. http://www.palliative.org/PC/ClinicalInfo/PcareTips/Hypercalcemia.html. Accessed 3/16/05. 20. Hillner BE. American Society of Clinical Oncology guideline on the role of bisphosphonates in breast cancer. American Society of Clinical Oncology Bisphosphonate Expert Panel. Journal of Clinical Oncology. 2000;18 (6):1378-91. Abstract 21. Hillner BE. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. Journal of Clinical Oncology.2003;21 (21):4042-57. Abstract. 22. CancerConsultants.com Treatment for Cancer-Related Bone Complications. Last updated 1/2005. 23. Weaver CH. Et al. CancerConsultants.com. Bone Complications and Cancer. Last updated 1/2005. 24. Coleman RE. Bisphosphonates: Clinical Experience. The Oncologist. 2004;9(suppl 4):14-27. 25. Berensen JR. Recommendations for zoledronic acid treatment of patients with bone metastases. Symptom management and supportive care. The Oncologist. 2005;10:52-62. 26. http://www.Oncolink.upenn.edu/resources/article.cfm?c. Zoledronic acid better than pamidronate for bone metastatses from breast cancer. 1/15/04. 27. Markowitz GS. Fine PL. Stack JI. Et al. Toxic acute tubular necrosis following treatment with zoledronate. International Society of Nephrology. 2003;64 (1):281-289. 28. Lipton A. Small E. Saad F. et al. The new bisphosphonate, Zometa, decreases skeletal complications in both osteolytic and osteoblastic lesions: a comparison to pamidronate. Cancer Investigation. 2002; 20(suppl 2):45-54. Abstract. 29. McCormack PL. Plosker GL. Ibandronic acid. A review of its use in the treatment of metastases of breast cancer. Drugs. 2006;66 (5):711-728. 30. Body JJ. Diel IJ. Lichinitser MR. Et al. Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases. Annals of Oncology. 2003;14:1399-1405. 31. Diel IJ. Body JJ. Lichinitser MR. Et al. Improved quality of life after long-term treatment with the bisphosphonate ibandronate in patients with metastatic bone disease due to breast cancer. European Journal of Cancer. 2005;40:1704-1712. 32. NIH Consensus Panel. Osteoporosis prevention, diagnosis, and therapy. JAMA 2001; 285(6): 785-95 33. Dawson-Hughes B. Gold DT. Rodbard HW. Et al. Physician's Guide to Prevention and treatment of osteoporosis. Developed by the National Osteoporosis Foundation in collaboration with American Academy of Orthopaedic Surgeons, American Academy of Physical Medicine and Rehabilitation, American College of Obstetricians and Gynecologists, American College of Radiology, American College of Rheumatology, American Geriatrics Society, American Medical Association, International Society for Physical Medicine and Rehabilitation and The Endocrine Society. Updated 9/05. 34. Small EJ. Smith MR. Seaman JJ et al. Combined analysis of two multicenter, randomized, placebo-controlled studies of pamidronate disodium for the palliation of bone pain in men with metastatic prostate cancer. Journal of Clinical Oncology. 2003; 21 (23):4277-4284. 35. Saad F. Gleason DM. Murray R. et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormonerefractory metastatic prostate carcinoma. Journal of the National Cancer Institute.2002; 94(19):1458-1468. 36. Kelly WK. Steineck G. Editorial. Bisphosphonates for men with prostate cancer: sifting through the rubble. Journal of Clinical Oncology. 2003; 21(23):4261-4262. 37. Ruggerio S. Gralow J. Marx RE. Et al. Practical guidelines for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in patients with cancer. Journal of Oncology Practice. 2006;2(1):7-14. 38. US Department of Health and Human Services. National Institutes of Health. Oral Complications of Cancer Treatment: What the oral health team can do. Publication No. 02-4372. 6/02.

Revision/Review Date: 05/2012 NOTE: Clinical reviewer must override criteria when, in his/her professional judgement, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA Injectable/Infusible Biological Agents Prior Authorization Criteria

PREFERRED STATUS: Preferred Biological agents. Require prior authorization ENBREL® (etanercept): 25 mg vial, 50 mg/mL single-use prefilled syringe HUMIRA® (adalimumab): 40 mg/0.8 mL kit, available as pen or syringe, 20 mg prefilled syringe TM SIMPONI (golimumab): 50 mg/0.5 mL vial STELARATM (ustekinumab): 45 mg/0.5 mL vial REMICADE® (infliximab): 100 mg/20 mL vial o (PLEASE NOTE: Remicade is only a preferred treatment option in the treatment of Crohn's Disease and Ulcerative Colitis). PREFERRED STATUS: Non-Preferred Biological Agents. Require prior authorization (Second Line) ACTEMRA® (tocilizumab): 20 mg/mL preservative-free single-use vial AMEVIVE® (alefacept): 15 mg lyophilized powder for injection CIMZIA® (certolizumab): 200 mg lyophilized powder for injection KINERET® (anakinra):100 mg/0.67 mL prefilled glass syringe ORENCIA® (abatacept): 250 mg preservative-free PA CRITERIA FOR APPROVAL FOR RHEUMATOID ARTHRITIS: · The patient is an adult (18 y/o) and has a documented clinical diagnosis of rheumatoid arthritis. · The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates and doses) of 3 months or more of therapy) of methotrexate AND then leflunomide (generic Arava®) or another disease-modifying antirheumatic treatment (DMARD) option (i.e. combination therapy consisting of methotrexate + sulfasalazine or hydroxychloroquine) or has another documented medical reason (e.g. intolerance, hypersensitivity) for not utilizing any of these therapies to manage their medical condition · If the request is for weekly dosing of Humira, for new members to the health plan, medical chart history indicates that the patient prior to becoming a member of the plan was prescribed and received weekly dosing of Humira · Documentation was submitted indicating that the member was evaluated for active or latent TB infection (i.e. tuberculin skin test). · The medication requested has a FDA approved indication for use in patients with rheumatoid arthritis and is being recommended and prescribed by a rheumatologist at an FDA-approved dosage · If the request is for a non-preferred agent, documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of at least two preferred biological agents. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR ANKYLOSING SPONDYLITIS · The patient is an adult (18 y/o) and has documented ankylosing spondylitis · The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of or has a documented medical reason for not taking at least two nonsteroidal anti-inflammatory drugs (NSAIDS) to manage their medical condition · The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of or has a documented medical reason for not taking a cyclo-oxygenase (COX)-2-selective inhibitors to manage their medical condition · Documentation was submitted indicating that the member was evaluated for active or latent TB infection (i.e. tuberculin skin test) · The medication requested has a FDA approved indication for use in patients with ankylosing spondylitis and is being recommended and prescribed by a rheumatologist at an FDA approved dosage · If the request is for a non-preferred agent, documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of at least two preferred biological agents. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR APPROVAL FOR CROHN'S DISEASE: · The member is an adult (18 y/o) and has a documented clinical diagnosis of moderate to severely active Crohn's disease. · The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates and doses) at therapeutic doses or has some documented clinically significant medical reason for not receiving conventional oral therapy (e.g. azathioprine, corticosteroids, 6-mercaptopurine) to manage their medical condition

· · ·

Documentation was submitted indicating that the member was evaluated for active or latent TB infection (i.e. tuberculin skin test) The medication requested has a FDA approved indication for use in patients with moderate to severely active Crohn's disease and is being recommended and prescribed by a gastroenterologist at an FDA-approved dosage If the request is for a non-preferred agent, documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of a preferred biological agent.

If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR APPROVAL FOR JUVENILE IDIOPATHIC ARTHRITIS: · The patient is a child (< 17 y/o) and within the FDA approved age range and has a documented clinical diagnosis of juvenile idiopathic arthritis. · The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates and doses-2 months or more of therapy) of at least one disease-modifying antirheumatic drug (DMARD) e.g. methotrexate), or has another documented medical reason (e.g. intolerance, hypersensitivity) for not utilizing any of these therapies to manage their medical condition · Documentation was submitted indicating that the member was evaluated for active or latent TB infection (i.e. tuberculin skin test) · The medication requested has a FDA approved indication for use in patients with juvenile idiopathic arthritis and is being recommended and prescribed by a rheumatologist or a pediatric rheumatologist at an FDA-approved dosage · If the request is for a non-preferred agent, documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of at least two preferred biological agents If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR APPROVAL FOR PSORIASIS: · The member is an adult (18 y/o) and has a documented clinical diagnosis of moderate to severe plaque psoriasis. · Documentation that the patient has had (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trials (including dates and doses) of at least 3 of the treatment bullet points listed below: o The use of topical steroids or has another documented medical reason for not using this therapy to manage their medical condition ® ® o The use of either Dovonex (calcipotriene), Tazorac (tazorotene), anthralin or a coal tar preparation or has another documented medical reason for not using any of these therapies to manage their medical condition o The use of methotrexate or has another documented medical reason (e.g. history of liver or kidney disease, pregnancy, severe cytopenia, alcoholics) for not using this therapy to manage their medical condition o The use of cyclosporine or has another documented medical reason for not using this therapy to manage their medical condition o The use of Soriatane® (acitretin) or has another documented medical reason for not using this therapy to manage their medical condition o The use of UVB phototherapy or PUVA (psoralen ­ oral or topical methoxsalen plus UVA therapy) or has another documented medical reason (e.g. pregnancy, skin cancer, hypersensitivity due to preexisting disease state - e.g. systemic lupus erythematus, cataracts) for not undergoing UVB phototherapy or PUVA to manage their medical condition · Documentation was submitted indicating that the member was evaluated for active or latent TB infection (i.e. tuberculin skin test) · The medication requested has a FDA approved indication for use in patients with moderate to severe plaque psoriasis and is being recommended or prescribed by a dermatologist at an FDA-approved dosage · If the request is for a non-preferred agent, documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of at least two preferred biological agents. If all of the above conditions are met, the request will be approved for up to a 6 month duration (except for Amevive). If the request is for Amevive, the request will be approved for a 1 month duration with additional monthly authorizations after receiving documentation that the member's CD4+ T-lymphocyte counts are 250 cells/µL up to 3 months of total treatment; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR PSORIATIC ARTHRITIS (PsA) · The patient is an adult (18 y/o) and has documented psoriatic arthritis.

·

·

· · ·

The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of 2 g/day for 3 months of sulfasalazine or has another documented medical reason for not taking sulfasalazine (e.g. predominantly axial symptoms, hepatotoxicity, GI intolerance) to manage their medical condition The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (3 months without any improvement at maximum doses) of methotrexate or has another documented medical reason for not taking methotrexate (e.g. predominantly axial symptoms, liver toxicity) to manage their medical condition Documentation was submitted indicating that the member was evaluated for active or latent TB infection (i.e. tuberculin skin test) The medication requested has a FDA approved indication for use in patients with psoriatic arthritis and is being recommended and prescribed by a rheumatologist a dermatologist at an FDA-approved dosage If the request is for a non-preferred agent, documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of at least two preferred biological agents.

If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR APPROVAL FOR USE IN ULCERATIVE COLITIS: · The patient is an adult (18 y/o) and has moderate to severe active ulcerative colitis. · The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) treatment failure after receiving an adequate trial of: o Sulfasalazine (3 to 6 g/day for 3 months), or mesalamine (1.2 to 2.4 g/day for 3 months), azathioprine (2 to 2.5 mg/kg/day), or 6-mercaptopurine (1.5 to 2 mg/kg/day), or oral corticosteroids or has a documented medical reason (GI intolerance, hypersensitivity, etc.) for not taking any of these medications to treat their medical condition · Documentation was submitted indicating that the member was evaluated for active or latent TB infection (i.e. tuberculin skin test) · The medication requested has a FDA approved indication for use in patients with moderate to severe active ulcerative colitis and is being prescribed at an FDA-approved dosage and is recommended or prescribed by a gastroenterologist. · If the request is for a non-preferred agent, documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of a preferred biological agent. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR RE-AUTHORIZATION FOR RHEUMATOID ARTHRITIS: · The member has been receiving the medication and documentation was provided that a rheumatologist has evaluated the member and recommends continuation of therapy · Documentation submitted indicates that the member has significantly clinically benefited from the medication · For members who require Humira 40 mg SC weekly then documentation must be submitted indicating that the member was compliant (consistent with pharmacy claims) at receiving at least 16 weeks of continuous Humira therapy every other week prior to the request for weekly dosing of Humira AND the member has a medical reason (e.g. intolerance, hypersensitivity, contraindication) for not receiving concomitant methotrexate · Once every 12 months, documentation was submitted indicating that the member was reevaluated for active or latent TB infection (i.e. tuberculin skin test, chest x-ray) · The medication is being prescribed for an FDA-approved indication at an FDA-approved dosage. If all of the above conditions are met, the request will be approved for a 6-month duration for Remicade requests and for a 12 month duration for requests for all other medications; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR RE-AUTHORIZATION FOR ANKYLOSING SPONDYLITIS, CROHN'S DISEASE, JUVENILE RHEUMATOID ARTHRITIS, PSORIATIC ARTHRITIS or ULCERATIVE COLITIS: · The medication is being recommended and prescribed by a dermatologist, gastroenterologist, rheumatologist, or a pediatric rheumatologist for an FDA-approved indication at an FDA-approved dosage · The member has been receiving the medication and documentation was provided that the prescriber has evaluated the member and recommends continuation of therapy · Documentation submitted indicates that the member has significantly clinically benefited from the medication If all of the above conditions are met, the request will be approved for a 6-month duration for Remicade requests and for a 12 month duration for requests for all other medications; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR RE-AUTHORIZATION FOR PSORIASIS:

· · ·

The medication is being recommended and prescribed by a dermatologist, gastroenterologist, rheumatologist, or a pediatric rheumatologist at an FDA-approved dosage. The member has been receiving the medication and documentation was provided that the prescriber has evaluated the member and recommends continuation of therapy Documentation submitted indicates that the member has significantly clinically benefited from the medication

If all of the above conditions are met, the request will be approved for a 6-month duration for Remicade requests and for a 12 month duration for requests for all other medication (except Amevive). If the request is for Amevive, the request will be approved for a 1 month duration with additional monthly authorizations after receiving documentation that the member's CD4+ T-lymphocyte counts are 250 cells/µL up to 3 months of total treatment. If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR AUTHORIZATION FOR OTHER NON-FDA APPROVED MEDICALLY ACCEPTED INDICATION: · The medication is prescribed for a non-FDA approved indication that is considered a medically accepted use of the medication per the medical compendia (i.e. Micromedex, DrugPoints, AHFS drug information) as defined by the Social Security Act · The medication is prescribed at a medically accepted dose per the medical compendia as defined by the Social Security Act · The medication is recommended and prescribed a specialist in the field to treat the member's respective medical condition · Documentation was submitted indicating that the member has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates, doses of medications) of all first line medical therapies as recommended by the medical compendia and standard care guidelines or has another documented medical reason (e.g. intolerance, contraindications) for not receiving or trying all first line medical treatment(s) · Documentation was submitted indicating that the member was evaluated for active or latent TB infection (i.e. tuberculin skin test) · If the request is for a non-preferred agent, documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of at least two preferred biological agents (if possible). If all of the above conditions are met, the request will be approved for up to a 6 month duration. if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR RE-AUTHORIZATION FOR OTHER NON-FDA APPROVED MEDICALLY ACCEPTED INDICATION: · Documentation that the medication is recommended or prescribed by a specialist for the respective treated disease state and is being prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, DrugPoints, AHFS) as defined by the Social Security Act · The medication is recommended and prescribed a specialist in the field to treat the member's respective medical condition · Documentation submitted indicates that the member has significantly clinically benefited from the medication. If all of the above conditions are met, the request will be approved for up to a 6 month duration. if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested.

FDA INDICATIONS:

Actemra Amevive Cimzia Enbrel Humira Kineret Orencia Remicade Simponi Stelara

Ankylosing Spondylitis

X

X

X

X

Crohn's Disease Juvenile Idiopathic Rheumatoid Arthritis

X

X

X ( 6 y.o.)

X ( 2 y.o.)

X ( 4 y.o.)

X ( 6 y.o.); monotx or + MTX

Psoriasis

X

X

X X; +/- MTX or other DMARD X; monotx or X; +/- MTX concomitant use or other with a non-TNFDMARD blocker DMARD

X

X

Psoriatic Arthritis X; monotx or concomitant use with a nonbiological DMARD

X; +/- MTX

Rheumatoid Arthritis

X

X; +/- MTX

X X +/- MTX X; monotx or concomitant use with a non-TNFX; with X; with blocker DMARD concomitant MTX concomitant MTX

Ulcerative Colitis

X

Acetmra is indicated for: · treatment of moderately- to severely-active rheumatoid arthritis in adult patients who have had an inadequate response to one or more TNF antagonists. It can be used as monotherapy or in combination with nonbiological disease-modifying antirheumatic drugs (DMARDs) Amevive is indicated for: · treatment of moderate-to-severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy Warning: Lymphopenia ­ Amevive induces dose-dependent reductions in circulating CD4+ and CD8+ T lymphocyte counts. A course of Amevive therapy should not be initiated in patients with a CD4+ T-lymphocyte count below normal. The CD4+ T lymphocyte counts of patients receiving Amevive® should be monitored weekly throughout the course of the 12 week dosing regimen. Dosing should be withheld if the CD4+ T-lymphocyte counts are below 250 cells/uL. The drug should be discontinued if the counts remain below 250 cells/uL for one month. Cimzia is indicated for: · reducing signs and symptoms of Crohn's disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy; treatment of adults with moderately to severely active rheumatoid arthritis Enbrel is indicated for: · reduction in signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in patients with moderately- to severely-active rheumatoid arthritis. It can be used either alone or in combination with MTX · reducing signs and symptoms of moderately- to severely-active polyarticular juvenile idiopathic RA in pediatric patients who are ages 2 and older · reducing signs and symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in patients with psoriatic arthritis. It can be used either alone or in combination with MTX; · treatment of adult patients with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy · reducing signs and symptoms in adult patients with active ankylosing spondylitis Humira is indicated for: · reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage and improving physical function in adult patients with moderately to severely active rheumatoid arthritis (as monotherapy or in combination with methotrexate or other DMARDs) · reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis (as monotherapy or in combination with DMARDs) · reducing signs and symptoms in adult patients with active ankylosing spondylitis · reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn's disease who have not adequately responded to conventional therapy or for reducing signs and symptoms and inducing clinical remission in these Crohn's disease patients if they have also lost response to or are intolerant to Remicade (infliximab) · treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate

·

reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older (as monotherapy or in combination with methotrexate)

Kineret is indicated for: · treatment of moderately- to severely-active rheumatoid arthritis in adult patients who have failed one or more disease-modifying antirheumatic drugs (DMARDs). It may be used alone or in combination with DMARDs (other than tumor necrosis factor-blocking agents) Orencia is indicated for: · treatment of moderately- to severely-active adult rheumatoid arthritis (RA); may be used as monotherapy or in combination with other DMARDs · treatment of moderately- to severely-active juvenile idiopathic arthritis (JIA). It may be used as monotherapy or in combination with methotrexate Note: Orencia (abatacept) should not be used in combination with Kineret (anakinra) or TNF-blocking agents. Remicade is indicated for: · use in combination with methotrexate for the reduction of signs and symptoms, to inhibit the progression of structural damage, and the improvement of physical function in patients with moderately to severely active rheumatoid arthritis · reduction of signs and symptoms and to induce and maintain clinical remission in adult and pediatric patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy · reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn's disease · reduction of signs and symptoms of active arthritis, to inhibit the progression of structural damage, and to improved physical function in patients with psoriatic arthritis · reducing signs and symptoms, achieving clinical remission (without the continued use of steroids) and mucosal healing, in patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy · treatment to reduce signs and symptoms in adult patients with active ankylosing spondylitis · treatment of adult patients with chronic severe plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate Simponi is indicated for: · treatment of adult patients with moderately to severely active rheumatoid arthritis in combination with methotrexate · treatment of adult patients with active psoriatic arthritis, either as monotherapy or in combination with methotrexate · treatment of adult patients with active ankylosing spondylitis Stelara is indicated for: · treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy

DOSAGE AND ADMINISTRATION: Actemra: · Rheumatoid Arthritis: The recommended starting dose of Actemra is 4 mg/kg, followed four weeks later by an increase to 8 mg/kg based on clinical response. Actemra is administered once every four weeks as a 60-minute single intravenous drip infusion. Doses exceeding 800 mg per infusion are not recommended. Amevive: · Psoriasis: The recommended dose is 7.5 mg given once weekly as an intramuscular injection of 15 mg once weekly for 12 weeks. Retreatment may be initiated as needed as long as the total lymphocyte and CD4+ T-cell counts are within normal range and a minimum of 12 weeks has passed since the last course of therapy. Warning: Lymphopenia ­ Amevive induces dose-dependent reductions in circulating CD4+ and CD8+ T lymphocyte counts. A course of Amevive therapy should not be initiated in patients with a CD4+ T-lymphocyte count below normal. The CD4+ T lymphocyte counts of patients receiving Amevive® should be monitored weekly throughout the course of the 12 week dosing regimen. Dosing should be withheld if the CD4+ T-lymphocyte counts are below 250 cells/uL. Discontinue Amevive if the counts remain below 250 cells/uL for one month. Cimzia: · Crohn's Disease: The recommended initial adult dose of Cimzia is 400 mg, given as 2 subcutaneous injections of 200 mg each initially and at weeks 2 and 4. In patients who obtain a clinical response, the recommended maintenance regimen is 400 mg every 4 weeks. · Rheumatoid Arthritis: The recommended dose of Cimzia for adult patients with rheumatoid arthritis is 400 mg (given as two subcutaneous injections of 200 mg) initially and at weeks 2 and 4, followed by 200 mg every other week. For maintenance dosing, Cimzia 400 mg every 4 weeks can be considered. Enbrel:

·

·

·

Ankylosing Spondylitis, adult RA, and Psoriatic Arthritis: The recommended dose of Enbrel is 50 mg per week, given as either a single subcutaneous injection or (2) 25 mg subcutaneous injections. Methotrexate, glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs (NSAIDs), or analgesics may be continued during treatment. Psoriasis: The recommended starting dose of Enbrel for adult patients is a 50 mg dose given twice weekly (administered 3 or 4 days apart) for 3 months followed by a reduction to a maintenance dose of 50 mg per week according to clinical studies. Starting doses of Enbrel 25 mg or 50 mg per week were also shown to be efficacious. Juvenile Arthritis: The recommended dose of Enbrel for children 2 to 17 years of age with active polyarticularcourse JRA is 0.8 mg/kg (up to a maximum of 50 mg per week). The 25 mg prefilled syringes are not recommended for pediatric patients weighing less than 31 kg (68 pounds). The 50 mg prefilled syringe or SureClick autoinjector may be used for pediatric patients weighing 63kg (138 pounds) or more. Glucocorticoids, NSAIDs, or analgesics may be continued during treatment with Enbrel. Concurrent use of MTX and higher doses of Enbrel have not been studied in pediatric patients.

Humira: · RA, Psoriatic Arthritis or Ankylosing Spondylitis: The recommended dose of Humira for adult patients is 40 mg administered every other week as a subcutaneous injection. Methotrexate (MTX), glucocorticoids, salicylates, non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, or other DMARDs may be continued during treatment with Humira. For RA, some patients not taking concomitant MTX, may derive additional benefit from increasing the dosing frequency of Humira to 40 mg SC every week. · Crohn's Disease: The recommended dose of Humira for adult patients is on day 1 to give 160 mg (four 40 mg injections on one day or two 40 mg injections per day for two consecutive days), followed by 80 mg two weeks later (on day 15), then two weeks after that (on day 29) begin the maintenance dose therapy of 40 mg every other week. · Juvenile Idiopathic Arthritis: The recommended dose of Humira for patients 4 to 17 years of age with polyarticular juvenile idiopathic arthritis is based on weight: Pediatric Patients (4 to 17 years) Dose: 15 kg (33 lbs) to < 30 kg (66 lbs): 20 mg every other week 30 kg (66 lbs): 40 mg every other week Methotrexate (MTX), glucocorticoids, salicylates, NSAIDs, or analgesics may be continued during treatment with Humira. Limited data is available for Humira treatment in pediatric patients who weigh less than 15 kg. · Plaque Psoriasis: The recommended dose of Humira is a 80 mg initial dose, followed by 40 mg every other week starting one week after initial dose. Kineret: · Rheumatoid Arthritis: The recommended dose is 100 mg/day administered daily by subcutaneous injection. Administer Kineret at the same time every day. Higher doses did not result in a higher response. Orencia: · Rheumatoid arthritis: Orencia should be administered as a 30-minute intravenous (IV) infusion at the dose specified in the following table. Following the initial administration, Orencia should be given at 2 and 4 weeks after the first infusion, then every 4 weeks thereafter. Orencia Dosing Body weight Dose Number of 250 mg vials < 60 kg 500 mg 2 60 to 100 kg 750 mg 3 > 100 kg 1g 4 · Juvenile Idiopathic Arthritis (JIA): The recommended dose of Orencia for patients age 6 to 17 years with JIA who weigh less than 75 kg is 10 mg/kg calculated based on the patient's body weight at each administration. Pediatric patients weighing 75 kg or more should be administered Orencia following the adult dosing regimen, not to exceed a maximum dose of 1000 mg. Orencia should be administered as a 30-minute intravenous (IV) infusion at the dose specified in the table above. Following the initial administration, Orencia should be given at 2 and 4 weeks after the first infusion, then every 4 weeks thereafter.

Remicade: · Rheumatoid Arthritis: 3 mg/kg given as an IV infusion followed with additional 3 mg/kg doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter. Give Remicade in combination with methotrexate. For patients who have an incomplete response, consideration may be given to adjusting the dose up to 10 mg/kg or treating as often as every 4 weeks (keeping in mind that at higher dosages there is an increase risk of serious infections). · Crohn's Disease or Fistulizing Crohn's Disease: 5 mg/kg given as an induction regimen at 0, 2, and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter. For patients who respond and then lose their response, consider treatment with 10 mg/kg. Patients who do not respond by week 14 are unlikely to respond with continued dosing; consider discontinuing Remicade in these patients.

· · ·

Psoriatic Arthritis and Plaque Psoriasis: The recommended dose is 5 mg/kg followed with additional 5 mg/kg doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter. For the treatment of psoriatic arthritis, Remicade can be used with or without methotrexate. Ankylosing Spondylitis: The recommended dose is 5 mg/kg followed with additional 5 mg/kg doses at 2 and 6 weeks after the first infusion, then every 6 weeks thereafter. Ulcerative Colitis: 5 mg/kg given as an induction regimen at 0, 2, and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of moderately to severely active ulcerative colitis.

Simponi: · Rheumatoid Arthritis: The recommended dose is 50 mg administered by subcutaneous (SC) injection once a month. For patients with rheumatoid arthritis, Simponi should be given in combination with methotrexate. Corticosteroids, non-biologic DMARDs, or NSAIDs may be continued during treatment with Simponi. · Psoriatic Arthritis and Ankylosing Spondylitis: The recommended dose is 50 mg administered by subcutaneous (SC) injection once a month. For patients with psoriatic arthritis or ankylosing spondylitis, Simponi may be given with or without methotrexate or other non-biologic DMARDs. Corticosteroids, non-biologic DMARDs, or NSAIDs may be continued during treatment with Simponi. Stelara: · Psoriasis: For patients weighing <100 kg (220 lbs), the recommended dose is 45 mg administered by subcutaneous injection initially and 4 weeks later, followed by 45 mg every 12 weeks. For patients weighing >100 kg (220 lbs), the recommended dose is 90 mg initially and 4 weeks later, followed by 90 mg every 12 weeks. In subjects weighing >100 kg, 45 mg was also shown to be efficacious. However, 90 mg resulted in greater efficacy in these subjects. REFERENCES: 1. Guidelines for the Management of Rheumatoid Arthritis; American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines; 2008 Update. Arthritis and Rheumatism 2008; 59(6): 762-84. 2. Humira Prescribing Information. Abbott Laboratories, March 2009. 3. Enbrel Product Information. Immunex Corporation. 4/2009. 4. Cimzia Prescribing Information. UCB, Inc. May 2009. 5. Orencia Prescribing Information. Bristol-Myers Squibb. 4/2008 6. Actemra Prescribing Information. Genentech, Inc. January 2010 7. Amevive Prescribing Information. Astellas Pharma US Inc. March 2009 8. Kineret Prescribing Information. Biovitrum. December 2009. 9. Remicade Prescribing Information. Centocor Ortho Biotech, Inc. November 2009 10. Simponi Prescribing Information. Centocor Ortho Biotech, Inc. November 2009 11. Stelara Prescribing Information. Centocor Ortho Biotech, Inc. November 2009 12. Saini R. Tutrone WD. Weinberg JM. Advances in therapy for psoriasis: an overview of infliximab, etanercept, efalizumab, alefacept, adalimumab, tazarotene, and pimecrolimus. Current Pharmaceutical Design. 11(2): 27380, 2005. 13. Callen JP, Krueger GG, et al. AAD consensus statement on psoriasis therapies; Journal of the American Academy of Dermatology 2003; 49:897-9. 14. Linden KG. Weinstein GD. Psoriasis: current perspectives with an emphasis on treatment. American Journal of Medicine. 107(6): 595-605, 1999 Dec. 15. Lebwohl M, Menter A, Koo J, Feldman R. Combination therapy to treat moderate to severe psoriasis; Journal of the American Academy of Dermatology 2004; 50:416-430. 16. Pardasani A, Feldman S, Clark A. Treatment of Psoriasis: An Algorithm-Based Approach for Primary Care Physicians. American Family Physician 2000;61(3):725-733. 17. Saini R. Tutrone WD. Weinberg JM. Advances in therapy for psoriasis: an overview of infliximab, etanercept, efalizumab, alefacept, adalimumab, tazarotene, and pimecrolimus. Current Pharmaceutical Design. 11(2):27f380, 2005. 18. Salvarani C, Cantini F, Olivieri I. Disease-Modifying Antirheumatic Drug Therapy for Psoriatic Arthritis. Clinical and Experimental Rheumatology 2002; 20(S28):S71-75. 19. Peyrin-Biroulet L, Laclotte C, Bigard M.A. Adalimumab Maintenance Therapy for Crohn's Disease with Intolerance or Lost Response to Infliximab: an open-label study; Alimentary Pharmacology & Therapeutics 2007; 25: 675-680. 20. Colombel J.F., Sandborn W, et. al. Adalimumab for Maintenance of Clinical Response and Remission in Patients with Crohn's Disease: The CHARM Trial; Gastroenterology 2007: 132: 52-65 21. Braun J, Pham T, Sieper J, et.al. International ASAS consensus statement for the use of anti-tumor necrosis factor agents in patients with ankylosing spondylitis; Ann Rheum Dis 2003; 62: 817-24. 22. Zochling Z, van der Heijde D, Burgos-Vargas R, et. al. ASAS/EULAR recommendations for the Management of Ankylosing Spondylitis; Ann Rheum Dis 2006; 65: 442-52. 23. Nast A, Kopp A, Augustin M, et al. German-evidence-based guidelines for the treatment of Psoriasis vulgaris (short version). Arch Dermatol Res 2007: 299: 111-138. Revision/Review Date: 11/2010 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA

Injectable/Infusible Osteoporosis Agents Prior Authorization Criteria

BONIVA INJECTION® (ibandronate sodium): 3 mg/3mL single use syringe ® FORTEO (teriparatide [rDNA origin] injection): 20mcg/dose in a 2.4ml prefilled pen TM PROLIA (denosumab): 60 mg/1mL ® RECLAST (zoledronic acid): 5 mg/100mL PA CRITERIA FOR APPROVAL FOR USE IN OSTEOPOROSIS: · Documentation was submitted which places the member into one of the following categories: 1) Postmenopausal woman or a male patient who has a bone mineral density (BMD) value consistent with osteoporosis (i.e., T-scores equal to or less than ­2.5) or who has had an osteoporotic fracture. 2) Postmenopausal woman or man over 50 with a T-score between -1 and -2.5 at the femoral neck or spine and a 10 year hip fracture probability >3% or a 10 year major osteoporosis-related fracture probability >20% based on the US-adapted WHO absolute fracture risk model. The patient has a documented (consistent with pharmacy claims data) treatment failure after receiving an adequate trial of the following therapies (including dates of treatment at maximum recommended doses of therapy) or has a documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not utilizing these therapies to manage their medical condition: o An oral bisphosphonate The patient is taking adequate Calcium and Vitamin D supplementation. · · If the request is for Boniva (ibandronate sodium) Injection or Prolia (denosumab), there must be a documented trial and failure or intolerance to Reclast (zoledronic acid) in females. · If the request is for Forteo (teriparatide [rDNA origin] injection), there must be a documented trial and failure or intolerance to Reclast (zoledronic acid) and then either Boniva Injection (ibandronate sodium) or Prolia (denosumab) in females or Reclast (zoledronic acid) in males. · The medication requested has a FDA approved indication for use in patients with osteoporosis and is being recommended and prescribed at a FDA approved dosage. If all of the above conditions are met, the request for Forteo will be approved for a 6-month duration and for all other medications the request will be approved for a 12-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR RE-APPROVAL FOR USE IN OSTEOPOROSIS: · The patient has documentation of clinical benefit from the medication. · The patient is taking adequate Calcium and Vitamin D supplementation. · If the request is for Forteo (teriparatide [rDNA origin] injection): o The prescribed dosage is within the FDA approved dosage range and does not exceed the therapy maximum of 2 years as indicated below under dosage and administration. o The medication requested has a FDA approved indication for use in patients with osteoporosis and is being recommended and prescribed at a FDA approved dosage. If all of the above conditions are met, the request for Forteo will be approved for a 6-month duration and for all other medications the request will be approved for a 12-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR APPROVAL FOR USE IN THE TREATMENT OR PREVENTION OF OSTEOPOROSIS DUE TO GLUCOCORTICOID THERAPY: · Documentation, including for what indication the patient will be, or is currently utilizing glucocorticoid therapy for a minimum of 12 months. · Documentation that the dosage of the glucocorticoid therapy is equivalent to a dose > 7.5 mg of prednisone daily if the request is for Reclast or >5 mg if the request is for Forteo. · Documentation (consistent with pharmacy claims data) of treatment failure after receiving an adequate trial of the following therapies (including dates of treatment at maximum recommended doses of

·

therapy) or a documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not utilizing an oral bisphosphonate to manage their medical condition. The medication requested has a FDA approved indication for use in patients for the treatment or prevention of osteoporosis and is being recommended and prescribed at a FDA approved dosage.

If all of the above conditions are met, the request for Forteo will be approved for a 6-month duration and Reclast will be approved for a 12-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR INITIAL APPROVAL IN PATIENTS WITH PAGET'S DISEASE: · Documentation of a confirmed diagnosis of Paget's disease. · Documentation (consistent with pharmacy claims data) of treatment failure after receiving an adequate trial of the following therapies (including dates of treatment at maximum recommended doses of therapy) or the patient has a documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not utilizing an oral bisphosphonate to manage their medical condition. · Documentation (from within 60 days of the request) that the patient has a serum alkaline phosphatase level of > two times the upper limit of normal OR the patient is symptomatic OR the patient is at risk for complication from Paget's disease. · The patient is taking adequate Calcium and Vitamin D supplementation. · The medication requested has a FDA approved indication for use in patients with Paget's disease and is being recommended and prescribed at a FDA approved dosage. If all of the above conditions are met, the request will be approved; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested.

PA CRITERIA FOR RE - APPROVAL IN PATIENTS WITH PAGET'S DISEASE: · Documentation of a confirmed diagnosis of Paget's disease. · The patient is taking adequate Calcium and Vitamin D supplementation. · If the patient is in need of redosing less than 6 months after their initial treatment: documentation (from within 60 days of the request) that the patient's serum alkaline phosphatase level has risen to > two times the upper limit of normal and/or never normalized after the initial treatment OR the patient is suffering from symptoms of Paget's disease is required. · The medication requested has a FDA approved indication for use in patients with Paget's disease and is being recommended and prescribed at a FDA approved dosage. If all of the above conditions are met, the request will be approved; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. FDA INDICATION: Indication Osteoporosis in postmenopausal women Osteoporosis in men Treatment of osteoporosis due to glucocorticoid therapy Prevention of osteoporosis due to glucocorticoid therapy Paget's disease Boniva injection X Forteo X X X Prolia X Reclast X X

X X

FDA INDICATION: Boniva injection is indicated for: · Treatment of osteoporosis in postmenopausal women.

Reclast is indicated for:

· · · · ·

The treatment of osteoporosis in postmenopausal women. In postmenopausal women with osteoporosis, Reclast reduces the incidence of fractures (hip, vertebral, and non-vertebral osteoporosisrelated fractures). The prevention of osteoporosis in postmenopausal women. The treatment to increase bone mass in men with osteoporosis. The treatment and prevention of glucocorticoid-induced osteoporosis in men and women who are either initiating or continuing systemic glucocorticoids in a daily dosage > 7.5 mg per day of prednisone and who are expected to remain on glucocorticoids for at least 12 months. The treatment of Paget's disease of bone in men and women. Treatment is indicated for patient's wit Paget's disease of bone with elevations in serum alkaline phosphatase of two times or higher than the upper limit of the age-specific normal reference range, or those who are symptomatic, or those at risk for complications from their disease.

Forteo injection is indicated: · For the treatment of postmenopausal women with osteoporosis who are at high risk for fracture, or who have failed or are intolerant of previous osteoporosis therapy. · To increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture. These include men with a history of osteoporotic fracture, or who have multiple risk factors for fracture, or who have failed or are intolerant to previous osteoporosis therapy. · Treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy (daily dosage equivalent to 5 mg or greater of prednisone) at high risk for fracture, defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy Prolia is indicated for: · For the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, Prolia reduces the incidence of vertebral, nonvertebral, and hip fractures DOSAGE AND ADMINISTRATION: Boniva: · Osteoporosis in Postmenopausal Women: The recommended dose is 3 mg given once every 3 months Forteo: · Osteoporosis in Postmenopausal Women/Men & Treatment and Prevention of GlucocorticoidInduced Osteoporosis: The recommended dosage is 20 mcg once a day administered as a subcutaneous injection into the thigh or abdominal wall. The length of therapy should be no longer than 2 years. Prolia: · Osteoporosis in Postmenopausal Women: The recommended dose is 60 mg administered as a single subcutaneous injection once every 6 months administered via subcutaneous injection in the upper arm, the upper thigh, or the abdomen. All patients should receive calcium 1000 mg daily and at least 400 IU vitamin D daily. If a dose of Prolia is missed, administer the injection as soon as the patient is available. Thereafter, schedule injections every 6 months from the date of the last injection. Reclast: · Treatment of Postmenopausal Osteoporosis/ Osteoporosis in Men & the Treatment and Prevention of Glucocorticoid-Induced Osteoporosis: The recommended dose is a 5 mg infusion once a year given intravenously over no less than 15 minutes. Patients must be adequately supplemented with calcium and vitamin D if dietary intake is not sufficient. An average of at least 1200 mg of calcium and 800-1000 IU of vitamin D daily is recommended. · Prevention of Osteoporosis in Postmenopausal Women: The recommended regimen in a 5 mg infusion given once every 2 years intravenously over no less than 15 minutes. Patients must be adequately supplemented with calcium and vitamin D if dietary intake is not sufficient. Postmenopausal women require an average of 1200 mg calcium and 800-1000IU vitamin D daily.

·

Paget's Disease of the Bone: The recommended dose is a 5 mg infusion. The infusion must be given over a constant infusion rate of no less than 15 minutes.

Reference: 1. Boniva Injection Prescribing Information. GlaxoSmithKline, March 2010. 2. Forteo® Prescribing Information. Eli Lilly and Company, January 2010. TM 3. Prolia Prescribing Information. Amgen, June 2010. 4. Reclast® Prescribing Information. Novartis, January 2010. 5. Dawson-Hughes B. Lindsay R, Khosla S. Et al. Physician's Guide to Prevention and treatment of osteoporosis. Developed by the National Osteoporosis Foundation in collaboration with American Academy of Orthopedic Surgeons, American Academy of Physical Medicine and Rehabilitation, American College of Obstetricians and Gynecologists, American College of Radiology, American College of Rheumatology, American Geriatrics Society, American Medical Association, International Society for Physical Medicine and Rehabilitation and The Endocrine Society. Updated 2008. 6. National Osteoporosis Foundation. Physician's guide to prevention and treatment of osteoporosis. http://www.nof.org/sites/default/files/pdfs/NOF_ClinicianGuide2009_v7.pdf. Accessed February 8, 2011. 7. Black DM, Delmas PD, Eastell R, et al. Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis. N Eng J Med 2007; 356(18): 1809-22. 8. McClung M, Recker R, Miller P, et al. Intravenous Zoledronic Acid 5 mg in the Treatment of Postmenopausal Women with Low Bone Density Previously Treated with Alendronate. Bone 2007; 45: 122-8. 9. Reid IR, Miller P, Lyles K, et al. Comparison of a Single Infusion of Zoledronic Acid with Risedronate for Paget's Disease. N Eng J Med 2005; 353: 898-908. 10. Siris ES, Lyles KW, Singer FR, Meunier PJ. Medical Management of Paget's Disease of Bone: Indications of Treatment and Review of Current Therapies. J Bone and Mineral Research 2006; 21(S2): 94-8. 11. Binkley N. Krueger D. Current osteoporosis prevention and management. Topics in Geriatric Rehabilitation. 2004; 21(1):17-29. 12. Olszynski WP, Davison KS, Adachi JD, et al. Osteoporosis in Men: Epidemiology, Diagnosis, Prevention, and Treatment. Clinical Therapeutics 2004; 26(1): 15-28. 13. Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009 Aug 20;361(8):756-65.

Revision/Review Date: 05/2011 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgement, the requested item is medically necessary.

Risperdal Consta® (risperidone): 12.5 mg/2ml, 25 mg/2ml, 37.5 mg/2ml, 50 mg/2ml syringes Invega® SustennaTM (paliperidone palmitate): 38 mg, 78 mg, 117 mg, 156 mg, 234 mg syringes

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA

PA CRITERIA FOR INITIAL AUTHORIZATION: PA Criteria for Initial Authorization 1. The member has a long-term history (>3 months) of oral anti-psychotic medication noncompliance AND documentation submitted indicates that the member had significant clinical decompensation or there is a high risk for decompensation and functional impairment (e.g. hospitalizations, safety risk) AND documentation of a drug adherence treatment plan was also submitted that indicates the member failed the following types of measures to improve compliance with a preferred oral medications and/or a reason for why any of the following measures were not implemented to improve compliance with a preferred oral medications as clinically applicable: · · · Psychosocial interventions Psychoeducational interventions that have a behavioral component and supportive services. Provided member with concrete instructions and problem-solving strategies (i.e. reminders, self-monitoring tools, cues, and reinforcements).

And/OR the member has a documented medical reason (i.e. documented treatment failure to maximum doses and/or has Intolerable side effects or drug interactions) for not using a preferred atypical antipsychotic medication. 2. 3. 4. Documentation submitted indicates that the medication is being prescribed for an FDA approved indication. For members requesting Invega Sustenna then a documented history of receiving oral risperidone (Risperdal®) and/or oral paliperidone (Invega). For members requesting Risperdal Consta then a documented history of receiving oral risperidone (Risperdal®) daily without any clinically significant side effects.

If all of the above conditions are met, the request will be approved with a 16-week duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR REAUTHORIZATION: 1. Documentation submitted indicates that the medication continues to be prescribed for its FDA approved indication. 2. Documentation submitted indicating how the member clinically improved or stabilized while receiving the medication. 3. Documentation submitted indicates that the member is tolerating medication. If all of the above conditions are met, the request will be approved with a 16-week duration, however for patients stable on a dose (e.g. > 6 months) can be approved for a 12 month duration. if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. FDA APPROVED INDICATIONS: Risperdal Consta is indicated: · For the treatment of schizophrenia. · As monotherapy or as adjunctive therapy to lithium or valprate for the maintenance treatment of Bipolar I Disorder Invega Sustenna is indicated for: · The acute and maintenance treatment of schizophrenia in adults DOSAGE AND ADMINISTRATION Risperdal Consta: · Risperdal Consta should be administered every 2 weeks by deep intramuscular (IM) deltoid or gluteal injection. · The recommended dose is 25mg IM every 2 weeks. Some members not responding to 25mg may benefit from a higher dose of 37.5mg or 50mg. The maximum dose should not exceed 50mg of Risperdal Consta every 2 weeks. No additional benefit was observed with dosages greater than 50mg of Risperdal Consta, however, a higher incidence of adverse effects was observed. · A lower dose of 12.5mg may be appropriate when clinical factors warrant dose adjustment, such as in patients with hepatic or renal impairment, for certain drug interactions that increase risperidone plasma concentration, or in patients who have a history of poor tolerability to psychotropic medications. The efficacy of the 12.5mg dose has not been investigated in clinical trails. Oral Risperdal (or another anti-psychotic medication) should be given with the first injection of Risperdal Consta and continued for 3 weeks (and then discontinued) to ensure that adequate therapeutic plasma concentrations are maintained. Based on FDA labeling, an upward dosage adjustment should not be made more frequently than every 4 weeks. The clinical effects of a dose adjustment should not be anticipated earlier than 3 weeks after the first injection with the higher dose. However, because it may take up to 8 weeks for the medication to reach steady state, and based on Texas Implementation of Medical Algorithms (TIMA) which recommends to evaluate a response to a dose of an anti-psychotic medication after a member has been on therapy for about 4 weeks, the anticipated full therapeutic effects for a given dose of Risperdal Consta may not occur until the member has received at least 12 weeks of therapy. Do not combine two different dosage strengths of Risperdal Consta in a single administration. Invega Sustenna:

·

Recommended starting dose of Invega Sustenna is a dose of 234 mg on treatment day 1 and 156 mg one week later, both administered in the deltoid muscle. The recommended monthly maintenance dose is 117 mg; some patients my benefit from lower or higher maintenance doses within the recommended range of 39 to 234 mg based on individual patient tolerability and/or efficacy. Table1. Doses of Invega and Invega Sustenna needed to attain similar paliperidone exposure at steady-state Formulation Invega Invega Sustenna Dosing Frequency Once Daily Once every 4 weeks 12 234 Dose (mg) 6 117 3 39-78

DOSAGE ADJUSTMENTS: Risperdal Consta Members with hepatic or renal impairment should be treated with titrated doses of oral Risperdal prior to initiating treatment with Risperdal Consta. The recommended starting dose is 0.5mg oral Risperdal bid during the first week, which can be increased to 1mg bid or 2mg once daily during the second week. If a dose of at least 2mg oral Risperdal is well tolerated, an injection of 25mg Risperdal Consta can be administered every 2 weeks. Alternatively, a starting dose of Risperdal Consta of 12.5mg may be appropriate. Oral supplementation should be continued for 3 weeks after the first injection until the main release of risperidone from the injection has begun. Invega Sustenna For patients with mild renal impairment (CrCl > 50 ml/min to < 80 ml/min), recommended starting treatment with a dose of 156 mg on treatment day 1 and 117 mg one week later, both administered in the deltoid muscle. Thereafter, follow with monthly injections of 78 mg in either the deltoid of gluteal muscle. Invega Sustenna is not recommended in patient with moderate or severe renal impairment. (CrCl < 50 ml/min). SWITCHING FROM OTHER ANTI-PSYCHOTICS: There are no systemically collected data to specifically address switching schizophrenic members from other anti-psychotics to either Risperdal Consta or Invega Sustenna, or concerning concomitant administration with other anti-psychotics. Risperdal Consta: Oral Risperdal (or another anti-psychotic medication) should be given with the first injection of Risperdal Consta and should be continued should be continued for 3 weeks after the first injection of Risperdal Consta to ensure that therapeutic concentrations are maintained until the main release phase of risperidone from the injection site has begun. For schizophrenic members who have never taken oral Risperdal, it is recommended to establish tolerability with oral Risperdal prior to initiating treatment with Risperdal Consta. Invega Sustenna: For patients who have never taken oral paliperidone or oral or injectable risperirone, tolerability should be established with oral paliperidone or oral risperidone prior to initiating treatment with Invega Sustenna. Previous oral antipsychotics can be discontinued at the time of initaion of treatment with Invega Sustenna. Patients previously stabilized on different doses of Invega Extended-Release tablets can attain similar paliperidone steady-state exposure during maintenance treatment with Invega Sustenna. References 1. Miller Alexander L, Hall Catherine S, et al. Texas Implementation of Medical Algorithms; Schizophrenia Module. Jan. 2003 Available from Internet: TIMA Schizophrenia Module http://www.mhmr.state.tx.us/centraloffice/medicaldirector/timascz1algo.pdf 2. Risperdal Constar Package Insert. Ortho-McNeil-Janseen Pharmaceuticals, Inc. May 2009. 3. Invega Sustenna Package Insert. Ortho-McNeil-Janseen Pharmaceuticals, Inc. July 2009. 4. Swainston Harrison T, Goa KL. Long-acting risperidone: a review of its use in schizophrenia. CNS Drugs, 18(2): 113-32, 2004. Revision/Review Date: 2/2010 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgement, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA FOR LOW MOLECULAR WEIGHT HEPARIN (LMWH) THERAPY

Arixtra® (fondaparinux): 2.5mg/0.5ml, 5mg/0.4ml, 7.5mg/0.6ml and 10mg/0.8ml pre-filled syringes Fragmin® (dalteparin): 2,500U/ml, 5,000U/ml, 7,500U/ml, 10,000U/ml, 12,500U/ml, 15,000U/ml 18,000U/ml (pre-filled syringes) and 95,000U multi-dose vials Innohep® (tinzaparin): 20,000U/ml multi-dose vials ® Lovenox (enoxaparin): 30mg/0.3ml, 40mg/0.4ml, 60mg/0.6ml, 80mg/0.8ml, 100mg/ml, 120mg/0.8ml, 150mg/ml (pre-filled syringes) and 300mg/3ml multi-dose vials Any Newly Marketed Low Molecular Weight Heparin (LMWH) PA CRITERIA FOR APPROVAL FOR USE IN DEEP VEIN THROMBOSIS (DVT) AND/OR PULMONARY EMBOLIS (PE): · The medication is being prescribed for the prevention and/or treatment of a DVT and/or PE. · Documentation of the patient's current weight. · The medication is being prescribed at a dose that is within FDA approved guidelines. · If the request is for a duration of therapy greater than 31 days then a letter of medical necessity that provides a valid medical reason why the member cannot be treated with Coumadin® or Heparin for long-term therapy (>31 days) must be submitted. If all of the above conditions are met, the request will be approved for up to a 31-day duration (unless greater duration of therapy is requested and medically necessary then will be approved for up to a 6 month duration); if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR APPROVAL FOR USE IN A PREGNANT MEMBER: · The medication is being prescribed for the prevention and/or treatment of a DVT and/or PE while the member is pregnant. · Documentation of the patient's current weight and expected due date (EDD). If the request is to continue LMWH treatment postpartum then documentation of the patient's actual or expected due date and current weight is required AND THEN up to 6 weeks of additional treatment may be authorized. · The medication is being recommended and prescribed by an obstetrician or a hematologist at a dose that is within FDA approved guidelines and/or is supported by the medical compendium as defined by the Social Security Act. If all of the above conditions are met, the request will be approved for up to a 6 month duration OR up until the patient's expected due date plus, if requested, up to an additional 6 weeks of treatment postpartum (whichever comes first); if all of the above criteria are not met, the request will be referred to a Medical Director for medical necessity review. PA CRITERIA FOR APPROVAL FOR USE IN MEMBER WITH CANCER: · The medication is being prescribed for the prevention and/or treatment of a venous thromboembolism (VTE) (a proximal DVT and/or PE) for a member with cancer. · Documentation of the patient's current weight. · The medication is being recommended and prescribed by an oncologist/hematologist at a dose that is within FDA approved guidelines and/or is supported by the medical compendium as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or American Society of Clinical Oncology (ASCO) standard of care guidelines. If all of the above conditions are met, the request will be approved for up to a 6 month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested.

REAUTHORIZATION CRITERIA FOR APPROVAL FOR USE IN MEMBER WITH CANCER BEYOND SIX MONTHS: · The medication is being for the prevention and/or treatment of a VTE for a member with cancer. · Documentation of the patient's current weight. · If the request is to continue therapy for longer than 6 months then the provider must document that the patient sill has active cancer OR then a letter of medical necessity must be submitted that provides a valid medical reason why the member needs to continue treatment and cannot be treated with Coumadin® for long-term therapy. · The medication is being recommended and prescribed by an oncologist/hematologist at a dose that is within FDA approved guidelines and/or is supported by the medical compendium as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or American Society of Clinical Oncology (ASCO) standard of care guidelines. If all of the above conditions are met, the request will be approved for up to a 6 month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. FDA INDICATION: Arixtra: Indicated for the prophylaxis of DVT, which may lead to PE, for: o Patients undergoing hip fracture surgery, including extended prophylaxis. o Patients undergoing hip or knee replacement surgery. o Patients undergoing abdominal surgery who are at risk for thromboembolic complications. Indicated for the treatment of: o Of acute DVT when administered in conjunction with warfarin sodium. o Of acute PE when administered in conjunction with warfarin sodium when the initial therapy is administered in the hospital. Fragmin: Indicated for the prophylaxis of DVT, which may lead to PE, for: o Patients undergoing hip replacement surgery. o Patients undergoing abdominal surgery who are at risk for thromboembolic complications. o Patients who are at risk for thromboembolic complications due to severely restricted mobility during acute illness. Indicated for the prophylaxis of ischemic complications in unstable angina and non-Q-wave MI when concurrently administered with aspirin therapy. Indicated for the extended treatment of symptomatic VTE (a proximal DVT and/or PE) to reduce the recurrence of VTE in patients with cancer. Innohep: Indicated for the treatment of acute symptomatic DVT, with or without PE, when administered in conjunction with warfarin. Lovenox: Indicated for the prophylaxis of DVT in: o Abdominal, knee and hip replacement surgery and medical patients with severely restricted mobility during acute illness. Indicated for the treatment of acute DVT for inpatient treatment with or without PE and outpatient treatment without PE. Indicated for the treatment of unstable angina and non-Q-wave myocardial infarction (MI). Indicated for the treatment of acute segment elevation myocardial infarction (STEMI) in patients. DOSAGE AND ADMINISTRATION:

Arixtra: o DVT/PE Treatment: the recommended dose is 5mg (for patients weighing less then 50kg), 7.5mg (for patient weighing between 50 -100kg) or 10mg (for patients weighing more than 100kg) by SQ injection once daily. The usual duration of therapy is 5 -9 days, however up to 26 days of treatment has been used. o DVT Prophylaxis Following Abdominal Surgery: In patients weighing less than 50kg the recommended dose is 2.5mg first administered 6 -8 hours after surgery, then daily. The usual duration of therapy is 5 -9 days, however up to 10 days have been used. o DVT Prophylaxis: following abdominal, hip repair or replacement, and/or knee replacement the recommended dose is 2.5mg SQ daily. The usual duration is 5 ­ 9 days, and up to 11 days administration has been tolerated. However hip fracture patients may require up to 32 days (perioperative and extended prophylaxis) has been tolerated. Fragmin: o DVT Prophylaxis: Abdominal or hip replacement surgery: 2500-5000 IU SQ daily for 1 day preop followed by 5-10 days of the same dose range. o Medical Patients with Severely Restricted Mobility during Acute Illness: the recommended dose of Fragmin is 5000 IU administered by SQ injection once daily, the usual duration of administration was 12 to 14 days. o Unstable angina/Non-Q-wave MI: the recommended dose is 120 IU/kg SQ every 12 hours in conjunction with low-dose oral aspirin therapy. The maximum recommended dose is 10,000 IU per 12 hours. The usual duration of therapy is 5 to 8 days. o Cancer related Venous Thromboembolism: the recommended dose for the first 30 days is 200 IU/kg SQ daily (dose not to exceed 18,000 IU daily), then for months 2 - 6 the recommended dose is 150 IU/kg SQ daily (not to exceed 18,000 IU daily). Dosing beyond 6 months has not been established. o For use in Pregnancy: for acute treatments of VTE dose based upon the manufacturer's recommendations and adjust for weight gain as the pregnancy progresses. A goal anti-factor Xa level is 0.5 to 1.2 U/ml. For prophylaxis of VTE a dose of 5000 ­ 7500 IU SC once daily dose adjusted to a peak anti-factor Xa level of 0.2 to 0.6U/mL. Innohep: o DVT Treatment: with or with out PE, the recommended dose is 175 anti-Xa units/kg of body weight SQ daily for at least 6 days and until the patient is adequately anticoagulated with warfarin. Lovenox: o DVT Prophylaxis: Hip or knee replacement surgery: 30mg SC every 12 hours, up to 14 days; hip replacement may also be dosed 40mg SC once daily SC x 21 days. o Abdominal surgery: 40mg SC once daily up to 14 days. o DVT/PE Treatment: 1mg/kg SC every 12 hours up to 17 days. o Unstable angina/Non-Q-wave MI: 1mg/kg SC every 12 hours in conjunction with oral aspirin therapy. The usual duration of therapy is 2 to 8 days. o Medical patients during acute illness: In medical patients at risk for thromboembolic complications due to severely restricted mobility during acute illness, the recommended dose is 40 mg once daily SC. The usual duration of administration is 6 to 11 days; up to 14 days has been well tolerated. o Pregnancy: For acute treatment of VTE, dose based upon the manufacturer's recommendations and should be adjusted for weight gain as the pregnancy progresses. A goal anti-factor Xa level is 0.5 to 1.2 U/mL. For prophylaxis of VTE a dose of 40mg SC once daily dose adjusted to a peak anti-factor Xa level of 0.2 to 0.6U. DOSAGE ADJUSTMENTS:

Arixtra: o The use of Arixtra is contraindicated in patients with severe renal impairment (creatinine clearance of < 30 ml/minute) o The use of Arixtra is contraindicated in patients who weigh less than 50 kg when used for prophylactic therapy in hip fracture, hip or knee replacement surgery, or abdominal surgery.

Fragmin: o When used in cancer patient with symptomatic VTE: If the patient's platelet count is between 50,000 ­ 100,000/mm3 the dose of Fragmin should be reduced by 2,500 IU until their platelet count recovers to > 100,000/mm3. If the patient's platelet count is < 50,000/mm3 Fragmin® should be discontinued until their platelet count is > 50,000/mm3. o When used in cancer patient with symptomatic VTE: with renal impairment (creatinine clearance < 30 ml/minute). Patients should have their anti-Xa levels monitored to determine the appropriate dose of Fragmin®. The target level for the anti-Xa is 0.5 ­ 1.5 IU/ml. When a patient's anti-Xa level the sampling should be done 4 ­ 6 hours after the Fragmin® dose and only after the patient has received 3 - 4 doses of Fragmin®. Innohep: o When used in patients with severe renal impairment (creatinine clearance < 30 ml/minute), Innohep® should be dosed with caution and the patient's anti-Xa level should be monitored. Lovenox: Dosage Regimens for Patients with Severe Renal Impairment (Creatinine Clearance < 30ml/minute) Indications Dosage Regimen Prophylaxis in abdominal, hip or knee replacement 30 mg administered SQ once daily surgery Prophylaxis in medical patients during acute illness 30 mg administered SQ once daily Inpatient treatment of acute DVT with or without PE, 1 mg/kg administered SQ once daily when given with warfarin Outpatient treatment of acute DVT without PE, when 1 mg/kg administered SQ once daily given with warfarin Prophylaxis of ischemic complications of unstable 1 mg/kg administered SQ once daily angina and non-Q-wave MI, when given with aspirin Treatment of acute ST-STEMI in patients < 75 years 30mg single IV bolus plus a 1 mg/kg SQ dose old followed by 1 mg/kg administered SQ once daily Treatment of acute ST-STEMI in patients >75 years 1 mg/kg administered SQ once daily (no initial old bolus) o Geriatric patients with acute ST-STEMI: for patients > 75 years old, do not given an initial bolus of Lovenox. Initiate dosing at 0.75 mg/kg SQ every 12 hours (maximum dose of 75 mg for the first two doses only) followed by 0.75 mg/kg SQ dosing for the remaining doses.

NCCN Clinical Practice Guidelines in OncologyTM: Venous Thromboembolic Disease; V.1.2010 Update. Innohep® Prescribing Information. DuPont Pharma, December 2008. Fragmin® Prescribing Information. Pfizer Pharmaceutical, April 2007. Arixtra® Prescribing Information. GlaxoSmithKline Pharmaceutical, January 2010. Lovenox® Prescribing Information. Sanofi-Aventis, December 2009. James AH. Prevention and Management of Venous Thromboembolism in Pregnancy. The American Journal of Medicine 2007; 120 (10B): S26-34. Ellison J, Walker ID and Greer IA. Antenatal use of enoxaparin for prevention and treatment of thromboembolism in pregnancy. British Journal of Obstetrics and Gynaecology 2000; 107: 1116-21.

REFERENCES:

1. 2. 3. 4. 5. 6. 7.

8. 9. 10. 11. 12. 13.

Lee AYY, Rickles FR, Julian JA, et al. Randomized Comparison of Low Molecular Weight Heparin and Coumarin Derivatives on the Survival of Patients with Cancer and Venous Thromboembolism. Journal of Clinical Oncology 2005; 23(10): 2123-29. Nishioka J, Goodin S. Low-molecular-weight heparin in Cancer-Associated Thrombosis: Treatment, Secondary Prevention, and Survival. Journal of Oncology Pharmacy Practice 2007: 13: 85-97. American College of Chest Physicians®: Antithrombotic Therapy for Venous Thromboembolic Disease: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. 2004; 126(3): 401S-28S. American College of Chest Physicians: Prevention of Venous Thromboembolism: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. 2004; 126(3): 338s-400s. Duplaga BA, Rivers CW and Nutescu E. Dosing and Monitoring of Low-Molecular-Weight Heparins in Special Populations. Pharmacotherapy 2001; 21(2): 318-34. Yusuf S, Mehta S, Afzal Rizwan, et al. Effects of Fondaparinux on Mortality and Reinfarction in Patients with Acute ST-Segment Elevation Myocardial Infarction: The OASIS-6 Randomized Trial. JAMA 2006; 295: 1519-30.

Revision/Review Date: 5/2010 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA FOR SELF INJECTABLE DISEASE MODIFYING IMMUNOMODULATORS FOR MULTIPLE SCLEROSIS (MS)

Avonex® (Interferon beta -1a): 30mcg kit (vial or pre-filled syringe) Betaseron®(Interferon beta -1b): 0.3-mg pre-filled syringe Copaxone® (Glatiramer Acetate) 20mg kit (pre-filled syringe) Extavia®(Interferon beta -1b): 0.3-mg pre-filled syringe) ® Rebif (Interferon beta -1a): 8.8 mcg, 22mcg, 44 mcg pre-filled syringes Newly Marketed Self-Injectable Disease Modifying Immunomodulator for MS

PA CRITERIA FOR INITIAL APPROVAL: The request is for an adult ( 18 y/o) member with relapsing/remitting MS (RRMS) or secondary progressive MS (SPMS) with a relapsing element. The medication was prescribed at an FDA approved dosage. Medication was recommended by a neurologist or prescribed by a neurologist. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. REAUTHORIZATION CRITERIA: Documentation sent indicates that the member is an adult ( 18 y/o) and has one of the following types of MS: RRMS or SPMS with a relapsing element. Documentation from medical chart was submitted indicating that the member has significantly clinically benefited from the medication. The medication was prescribed at an FDA approved dosage. Medication was recommended by a neurologist or prescribed by a neurologist. If all of the above conditions are met, the request will be approved for up to a 12-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. FDA INDICATIONS: Avonex is indicated for the treatment of relapsing forms of multiple sclerosis to slow the accumulation of physical disability and decrease the frequency of clinical exacerbations. Safety and efficacy in members with chronic progressive multiple sclerosis have not been evaluated. Betaseron is indicated for the treatment of relapsing forms of MS to reduce the frequency of clinical exacerabations. Patients with multiple sclerosis in whom efficacy has been demonstrated include patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis. Copaxone is indicated for the reduction of the frequency of relapses in members with RRMS, including patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis. Copaxone has NOT been formally evaluated in combination with interferon beta. Extavia is indicated for the treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations. Patients with multiple sclerosis in whom efficacy has been demonstrated include patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis. Rebif is indicated for the treatment of relapsing forms of multiple sclerosis to decrease the frequency of clinical exacerbations and delay the accumulation of physical disability. Efficacy in chronic progressive MS has not been established. DOSAGE AND ADMINISTRATION: Avonex: 30 micrograms intramuscularly once a week and sites for injection include thighs or upper arms.

Betaseron: 0.25 mg subcutaneously (SC) every other day. Start dose at 0.0625 mg (0.25 mL) SC every other day and titrate dose by increasing dose over six weeks. Recommended Titration Betaseron Dose Volume 25% 0.0625 mg 0.25 mL Weeks 1-2 50% 0.125 mg 0.50 mL Weeks 3-4 75% 0.1875 mg 0.75 mL Weeks 5-6 Week 7+ 100% 0.25 mg 1.0 mL Copaxone: 20 mg/day injected SC and sites for injections include arms, abdomen, hips, and thighs. Extavia: 0.25 mg subcutaneously (SC) every other day. Start dose at 0.0625 mg (0.25 mL) SC every other day and titrate dose by increasing dose over six weeks. Extavia dosing titration schedule Recommended Titration Extavia Dose Volume 25% 0.0625 mg 0.25 mL Weeks 1-2 50% 0.125 mg 0.50 mL Weeks 3-4 75% 0.1875 mg 0.75 mL Weeks 5-6 Week 7+ 100% 0.25 mg 1.0 mL Rebif: 22 mcg or 44 mcg injected SC 3 times weekly, if possible at the same time (in the late afternoon or evening) on the same 3 days at least 48 hours apart each week and to rotate SC injection sites. It is best to start members at 20% of prescribed dose 3 times/week and increase dose over a 4 week period to target dose. A titration pack containing 8.8 mcg and 22 mcg syringes is available for use during titration period. Rebif dosing titration schedule Recommended titration Titration dose for Rebif Titration dose for Rebif (% of final dose) 22 mcg 44 mcg 20% 4.4 mcg 8.8 mcg Weeks 1-2 50% 11 mcg 22 mcg Weeks 3-4 Weeks 5+ 100% 22 mcg 44 mcg BOX 1: TREATMENT FAILURE:

A member may be considered to have failed treatment if any of the following are documented: 1. 2. 3. Member who has an attack rate (relapse) of more than 1 per year, fails to show a reduction in relapse rate, or continues to experience attacks (relapses) at a rate similar to that found before starting therapy** Member who has incomplete recovery (cumulative residual abnormalities sustained for 6 months) from repeated attacks, particularly as the EDSS score increases. ** Member experiences an annual increase in the EDSS (Expanded Disability Status Scale) of 1 point from a previous score of 3 to 5.5, or 0.5 point increase from a previous score of 6.0 or greater in the absence of clinical attacks or other documentation of clinically significant disability progression. ** Member who develops new or recurrent brainstem or spinal cord lesions as seen on MRI. ** Members experiencing relapses affecting multiple neurologic symptoms, and those accumulating residual impairments in multiple neurologic systems. ** Members who have progressive motor, cognitive or sensory impairment sufficient to disrupt their daily activities irrespective of changes on neurologic examination, provided the influence of depression, medications or superimposed concurrent disease is ruled out. Examples include: loss of endurance in sustaining activity, forced alterations in activities of daily living, muddled thinking, impaired concentration and mental processing and fatigue. ** Members who have new or enlarging T2 lesions, increase in brain atrophy on MRI, or new T1 Gd enhancing lesions on MRI accompanied by changes in the ability to perform daily activities.**

4. 5. 6.

7.

Kurtzke Expanded Disability Status Scale (EDSS) Rating Status Normal Neurological Exam No Disability, minimal symptoms No disability, minimal signs in more than one area Slightly more disability in one area Slightly greater disability in two areas Moderate disability in one area but still walking independently Walking independently but with moderate disability in one area and more than minimal disability in several others 4.0 Walking without aid, self-sufficient, up and about some12 hours a day despite relatively severe disability; able to walk without aid or rest some 500 meters 4.5 Walking without aid, up and about much of the day, able to work a full day, may have some limitation of full activity or require some help, relatively severe disability but able to walk without aid or rest some 300 meters. 5.0 Walking without aid or rest for about 200 meters, disability severe enough to impair full daily activities, can work a full day without special provisions 5.5 Ambulatory without aid or rest for about 100 meters; disability severe enough to prevent full daily activities 6.0 Intermittent or unilateral constant assistance (cane, crutch, brace) required to walk about 100 meters with or without resting 6.5 Needs canes, crutches, braces to walk for 20 meters without resting 7.0 Unable to walk beyond five meters even with aid; mostly confined to a wheelchair; wheels self in standard wheelchair and transfers alone; up and about in wheelchair some 12 hours a day 7.5 Unable to take more than a few steps; restricted to wheelchair; may need aid in transfer; wheels self but cannot carry on in standard wheelchair a full day; may require motorized wheelchair 8.0 Essentially restricted to bed, chair, or wheelchair, but may be out of bed itself much of the day; retains many self-care functions; generally has effective use of arms 8.5 Essentially restricted to bed much of day; has some effective use of arms; retains some self-care functions 9.0 Helpless bed patient; can communicate and eat 9.5 Totally helpless bed patient; unable to communicate effectively or eat/swallow 10.0 Death due to MS

Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology.1983;33:1444-1452.

0 1.0 1.5 2.0 2.5 3.0 3.5

REFERENCES:

1. National Multiple Sclerosis Society. Expert Opinion Paper. Medical advisory board of the National MS Society. Treatment recommendations for physicians. Changing therapy in relapsing multiple sclerosis: Considerations and recommendations of a task force of the National MS Society.2004. Available at www.nationalmssociety.org/PRC.asp National Multiple Sclerosis Society. Expert Opinion Paper. Medical advisory board of the National MS Society. Treatment recommendations for physicians. Disease management consensus statement.2005. Available at www.nationalmssociety.org/PRC.asp Cohen BA. Khan O. Jeffery DR. et al. Identifying and treating patients with suboptimal responses. Neurology.2004;63(Suppl 6):S33S40. Lee MA. Smith L. Palace J. et al. Spatial mapping of T2 and gadolinium-enhancing T1 lesion volumes in multiple sclerosis: evidence for distinct mechanisms of lesion genesis.? Brain.199;122:1261-1270. Rovaris M. Comi G. Filippi M. MRI markers of destructive pathology in multiple sclerosis-related cognitive dysfunction. Journal of the Neurological Sciences.2006;245:111-116. Brex P. Ciccarelli O. O'Riordan J. et al. A longitudinal study of abnormalities on MRI and disability from MS. The New England Journal of Medicine.2002;246(3):158-164. Miller DH. Grossman RI. Reingold SC. Et al The role of magnetic resonance techniques in understanding and managing MS. Brain.1998;121:3-24. Lycklama GJ. Van Walderveen MAA. Castelijns JA. Et al. Brain and spinal cord abnormalities in multiple sclerosis. Correlation between MRI parameters, clinical subtypes and symptoms. Brain.1998;121:687-697. O'Riordan JI. Thompson AJ. Kingsley DPE.et al. The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10year follow-up. Brain.1998;121:495-503. Rooney WD. Coyle PK. Recent advances in the neuroimaging of MS.Current Neurology and Neuroscience Reports.2005;5:217-224. Polman CH, O'Connor PW, Havrdova E, et al: A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354(9): 899-910. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology.1983;33:14441452. Rovaris M. Comi G. Filippi M. MRI markers of destructive pathology in multiple sclerosis-related cognitive dysfunction. Journal of the Neurological Sciences.2006;245:111-116.

2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

14. Polman CH. Reingold SC. Edan G. et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Annals of Neurology.2005;58:840-846. 15. Rudick, RA. Lee JC. Simon J. Fisher E. Significance of T2 lesions in multiple sclerosis: A 13-year longitudinal study. Annals of Neurology.2006;60:236-242. 16. Rieckmann P. Toyka KV. Escalating immunotherapy of multiple sclerosis. New aspects and practical application. Multiple Sclerosis Therapy Consensus Group (MSTCG). Journal of Neurology. 2004;251:1329-1339. 17. Leary SM. Porter B. Thompson AJ. Multiple sclerosis: diagnosis and the management of acute relapses. Postgraduate Medicine Journal. 2005;81:302-308. 18. Rio J. Nos C. Tintore M. et al. Assessment of different treatment failure criteria in a cohort of RRMS patients treated with interferon : implications for clinical trials. Annals of Neurology. 2002;52:400-406. 19. Rio J. Nos C. Tintore M. et al. Defining the response to interferon- in RRMS patients. Annals of Neurology.2006;59:344-352. 20. Avonex® Prescribing Information. Biogen Idec, Inc. 06/2011. 21. Betaseron® Prescribing Information. Berlex, Inc. 5/2010. 22. Copaxone® Prescribing Information. TEVA Neurosciences. 02/2009. 23. Extavia® Prescribing Information. Novartis Pharmaceuticals Corp. 8/2009 24. Rebif® Prescribing Information. Serono, Inc 09/2011 25. Disease modifying therapies in multiple sclerosis: Report of the Therapeutics and Technology, Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology. 58(2):169-178, January 22, 2002. 26. Morrow T, Brown J, Smith C, Thrower B. Considerations for the treatment of multiple sclerosis in the managed care setting. Formulary 2003; 38 (11).

Revision/Review Date: 02/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

PRIOR AUTHORIZATION PROCESS FOR INJECTABLE/SPECIALITY MEDICATIONS WITH NO SPECIFIC PRIOR AUTHORIZATION PROTOCOL

Initial Approval 1. The request for the medication is for an FDA approved indication, and/or is used for a medical condition that is supported by the medical compendium (i.e. Micro Medex, American Hospital Formulary Service, DrugPoints, Drug Package Insert, or the standard of care guidelines) as defined in the Social Security Act 1927 and/or per recognized standard of care guidelines. There is no formulary or plan preferred medication alternatives, OR there is a documented medical reason (i.e. medical intolerance, treatment failure, etc.) for why a formulary or plan preferred medication couldn't be used to treat the member's condition. Prescribed dosing of medication is within FDA approved indications and/or is supported by the medical compendium as defined above and/or per recognized standard of care guidelines.

2.

3.

If all of the above conditions are met, the request will be approved for up to 16 weeks or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per recognized standard of care guidelines; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Reauthorization of Medication 1. The prescribing physician has provided documentation as to the clinical benefits of the medication supporting continued treatment, OR the medication is being continued in accordance with the recommended time as defined by FDA drug package insert, per recommendations of the medical compendium as described above, or per recognized standard of care guidelines. Prescribed dosing of medication is within FDA approved indications or per supported by the medical compendium as defined above and/or per recognized standard of care guidelines.

2.

If all of the above conditions are met, the request will be approved for up to a 6 month duration or as recommended per FDA approved indications and/or as defined by medical compendium as defined above and/or per recognized standard of care guidelines; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Revision/Review Date: 8/2011 Associated Policy: Prior Authorization of Prescription Drugs 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA PROCRIT® (epoetin alfa): 2,000 units/ml, 3,000 units/ml, 4,000 units/ml, 10,000 units/ml, 20,000 units/ml, 40,000 units/ml PREFERRED PRODUCT: ARANESP® PREFERRED (for selected indications) PA CRITERIA FOR APPROVAL: · The necessary lab work (listed below) is performed within 30 days of the date the request is submitted and is either documented on the PA form or submitted with the request -Hemoglobin -Hematocrit -Serum ferritin -Transferrin saturation (TSAT) -Serum iron -Total Iron Binding Capacity (TIBC) -Vitamin B12 level -Folate level -Erythropoietin level (for HIV related anemia) · Documentation submitted indicates the member has Chronic Kidney Disease related anemia and/or Chemotherapy related anemia, or an anemia related to some other medical condition.

If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. If all of the above conditions are met, place the member into one of the following categories based on diagnosis: -Treatment of anemia of Pre-dialysis in chronic kidney disease patients: go to Section I -Treatment of anemia in cancer patients undergoing chemotherapy: go to Section II -Prescribed for anemia in HIV and/or Zidovudine-treated HIV disease: go to Section III -Reduction of allogeneic blood transfusion in surgery patients: go to Section IV -Prescribed for Ribavrin Induced anemia: go to Section V -Prescribed for other Medically Acceptable Indications go to Section VI Section I: PA Criteria for Approval for anemia of Pre-dialysis chronic kidney disease Place the member into one of the following categories based on the members Procrit® treatment history. Procrit® treatment initial request (Part A) Reauthorization of Procrit® (Part B)

Part A: Procrit® treatment initial request · · · · · If the member has chronic renal failure, the member has a hemoglobin level < 10 g/dL OR if the member is new to the health plan and was receiving Procrit® at the previous health plan the member has a documented (submitted lab result dated within 30 days of request) hemoglobin <12 g/dL Procrit® ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section). The member has had a documented treatment failure at optimal doses of Aranesp® and/or intolerance to Aranesp®, and/or some other documented clinically significant reason for not using Aranesp® to treat their anemia. Documentation submitted indicates that the member is or will be prescribed maintenance iron therapy (>200 mg elemental iron orally daily or periodic IV supplementation), or if not receiving iron supplementation is having percentage transferrin saturation and ferritin levels checked every 2 months. If the member has low vitamin B12 levels and/or Folate levels, documentation submitted indicates that the member is or will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated.

·

If the member is iron deficient (ferritin concentration <100 ng/mL and/or percentage transferrin saturation < 20%), the member is in the process of receiving either oral or IV iron supplementation or the treatment plan is to start iron therapy and will be having percentage transferrin saturation and ferritin levels monitored.

If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/mL and the transferrin saturation are > 20-55%) and not vitamin B-12 deficient and not folate deficient, OR up to a 1 month temporary supply if the member is functionally iron deficient (ferritin concentration < 100 ng/mL and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient. If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Part B: Reauthorization Criteria for Procrit® · If the member has chronic renal failure, and has been receiving therapy and their hemoglobin is <11 g/dL(submitted lab result dated within 30 days of request), OR if hemoglobin (submitted lab result dated within 30 days of request) is > 11g/dL while <12 g/dL and one of the following apply: a. Ordered dose of Procrit® is reduced by 25% of previous dose if the member's Hgb is increasing and approaching 12 g/dl OR increases by more than 1 g/dl in a 2 week period, b. Ordered dose of Procrit® was increased and Hgb increase rate was < 1g/dL over the past 4 weeks AND the member has adequate iron stores c. No more than 1 dosage adjustment per 4 week intervals occurs If the member had a normal vitamin B12 and Folate levels on the initial request OR had a low vitamin B12 and/or Folate level but has subsequently been placed on the appropriate supplementation then repeat vitamin B12 and Folate lab results are not needed until 1 year after the initial request. However if the patient was deficient in either vitamin B12 and/or Folate based on lab results from the initial request and are NOT receiving the appropriate supplementation then repeat vitamin B12 and Folate lab results must be submitted dated within 30 days of the request. The member's percentage transferrin saturation is greater than 20% and Ferritin is greater than 100 ng/ml and the member is receiving iron supplementation, if not receiving iron supplementation percentage transferrin saturation and Ferritin levels are being monitored every 2 months Procrit® ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section)

·

· ·

If all of the above conditions are met, the request will be approved for up to a 3-month duration, if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/mL and the transferrin saturation are > 20-55%) and not vitamin B-12 deficient and not folate deficient, OR up to a 1 month temporary supply if the member is functionally iron deficient (ferritin concentration < 100 ng/mL and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient. If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section II: PA Criteria for Approval for anemia cancer patients on chemotherapy: Place the member into one of the following categories based on the members Aranesp® treatment history. Procrit® treatment initial request (Part A) Reauthorization of Procrit® (Part B)

Part A: Aranesp® treatment initial request · · · The member has a documented hemoglobin < 10 g/dL OR if the member is new to the health plan and was receiving Procrit® at the previous health plan and the member has a documented hemoglobin < 12g/dL Procrit® ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) The member has had a documented treatment failure at optimal doses of Aranesp® and/or intolerance to Aranesp®, and/or some other documented clinically significant reason for not using Aranesp® to treat their anemia.

·

Documentation that the patient is currently receiving chemotherapy (along with documentation of the start and end date of the current course of chemotherapy). Treatment with Procrit® should be discontinued at the completion of a course of chemotherapy.

If all of the above conditions are met, the request will be approved for up to a 6-month duration OR till the end of current course of chemotherapy (whichever comes first), if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Part B: Reauthorization Criteria for Procrit® · · · The member has been receiving therapy and their hemoglobin is < 12 g/dL Procrit® ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) If the dose of Procrit® is being increased and/or patient's hemoglobin level has decreased from the previous request then recent (within 30 days of the request) ferritin, percentage transferrin saturation, Vitamin B12 and Folate levels are to be submitted. In addition: o If the member is iron deficient (ferritin concentration <100 ng/mL and/or percentage transferrin saturation < 20%), AND in the process of receiving either oral or IV iron supplementation OR the treatment plan is to start iron therapy along with having the percentage transferrin saturation and ferritin levels monitored. o If the member has low Vitamin B12 levels and/or Folate levels, documentation submitted indicates that the member is OR will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated.

If all of the above conditions are met, and the member is not functionally iron (ferritin concentration is > 100-800 ng/mL and the transferrin saturation are > 20-55%), Vitamin B-12 and Folate deficient OR if the member is iron, vitamin B12 and/or folate deficient and receiving the proper supplementation, the request will be approved for up to a 6-month duration OR till the end of current course of chemotherapy (whichever comes first). However, up to a 1 month temporary supply will be approved if the member is functionally iron (ferritin concentration < 100 ng/mL and/or percentage transferrin saturation < 20%) and/or Vitamin B-12 or Folate deficient AND not receiving OR planning to start the proper supplementation. If the above criteria is not met, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section III: PA Criteria for Approval for Treatment of HIV and/or Zidovudine-treated HIV disease Place the patient into one of the following: - Procrit treatment initial request (Part A) - Reauthorization of Procrit (Part B) Part A: Procrit treatment initial request · · · · · The member has a hemoglobin level < 11 g/dL OR if the member is new to the health plan and was receiving Procrit at the previous health plan the member has a documented (submitted lab result dated within 30 days of request) hemoglobin <12 g/dL Patient has been receiving a highly active antiretroviral therapy (HAART) regimen for the past 35 days. Documentation, within 30 days of the request, that the patient has an erythropoietin level < 500 milliunits/mL and receiving < 4200 mg/week of Zidovudine treatment. If the member has low vitamin B12 levels and/or Folate levels then documentation submitted that indicates the member is or will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated. If the member is iron deficient (ferritin concentration <100 ng/mL and/or percentage transferrin saturation < 20%), documentation is submitted indicating that the member is in the process of receiving either oral or IV iron supplementation (>200 mg elemental iron orally daily or periodic IV supplementation) or the treatment plan is to start iron therapy and then have the percentage transferrin saturation and ferritin levels monitored. The requested dose is in accordance with the recommended dosing guidelines as outlined in the dosage and administration section for HIV patients below.

·

If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/mL and the transferrin saturation are > 20-55%) and not vitamin B-12 deficient and not folate deficient, OR a temporary supply of up to 1 month may be authorized if the member is functionally iron deficient (ferritin concentration < 100 ng/mL and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested.

Part B: Reauthorization Criteria for Procrit · If the member has been receiving therapy and their hemoglobin is < 11 g/dL(submitted lab result dated within 30 days of request), OR if hemoglobin (submitted lab result dated within 30 days of request) is > 11g/dL < 12 g/dL & one of the following apply: a. The ordered dose of Procrit is reduced by 25% of previous dose if the rate of Hgb increase was > 1g/dL over a two week period OR the Hgb is increasing and approaching 12 g/dL. b. The ordered dose of Procrit is increased by 25% of previous dose if the patient's Hgb has not increased by 1 g/dL over a 4 weeks period (See Dosage and Administration section) OR the patient's Hgb falls below 10 g/dL. c. An increase in dose does not occur more than once per month. Patient is currently receiving HAART therapy. If the member had a normal vitamin B12 and Folate levels on the initial request OR had a low vitamin B12 and/or Folate level but has subsequently been placed on the appropriate supplementation then repeat vitamin B12 and Folate lab results are not needed until 1 year after the initial request. However if the patient was deficient in either vitamin B12 or Folate levels based on lab results from the initial request and is NOT receiving the appropriate supplementation then repeat vitamin B12 and Folate lab results must be submitted dated within 30 days of the request. If the member is iron deficient (ferritin concentration <100 ng/mL and/or percentage transferrin saturation < 20%), the member is in the process of receiving either oral or IV iron supplementation or the treatment plan is to start iron therapy. Procrit ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section)

· ·

· ·

If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/mL and the transferrin saturation are > 20-55%) OR a temporary supply of up to 1 month may be authorized if the member is functionally iron deficient (ferritin concentration < 100 ng/mL and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section IV: PA Criteria for Approval for Reduction of Allogeneic Blood Transfusion in Surgery Patients · The member has a hemoglobin level >10 to < 13 g/dL (submitted lab result dated within 30 days of request). · The member is scheduled for an elective noncardiac, nonvascular surgery and need to reduce the need for allogeneic blood transfusions. · The patient has normal iron stores and is, or will be, receiving adequate iron supplementation · The patient is starting therapy and the dose is within the starting dosage range [300 U/kg/day SC for 10 days before surgery, on the day of surgery and for 4 days after surgery OR 600 U/kg SC in once-weekly doses (21, 14 and 7 days before surgery) plus a fourth dose on the day of surgery] If all of the above conditions are met, the request will be approved with a 1-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section V: PA Criteria for Approval for Ribavirin Induced Anemia Place the patient into one of the following: - Procrit treatment initial request (Part A) - Reauthorization of Procrit (Part B)

Part A: Procrit treatment initial request · · · · The member has a hemoglobin level < 11 g/dL OR if the member is new to the health plan and was receiving Procrit at the previous health plan the member has a documented (submitted lab result dated within 30 days of request) hemoglobin <12 g/dL Procrit ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) If the member has low vitamin B12 levels and/or Folate levels then documentation submitted that indicates the member is or will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated. If the member is iron deficient (ferritin concentration <100 ng/mL and/or percentage transferrin saturation < 20%), the member is in the process of receiving either oral or IV iron supplementation (>200 mg elemental iron orally daily or periodic IV supplementation) or the treatment plan is to start iron therapy and then have the percentage transferrin saturation and ferritin levels monitored. Patient is currently receiving ribavirin therapy and initiated therapy 20 weeks ago.

·

If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/mL and the transferrin saturation are > 20-55%) and not vitamin B-12 deficient and not folate deficient, OR a temporary supply of up to 1 month may be authorized if the member is functionally iron deficient (ferritin concentration < 100 ng/mL and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Part B: Reauthorization Criteria for Procrit ® · If the member has been receiving therapy and their hemoglobin is < 11 g/dL(submitted lab result dated within 30 days of request), OR if hemoglobin (submitted lab result dated within 30 days of request) is > 11g/dL < 12 g/dL & one of the following apply: a. The ordered dose of Procrit is reduced by 25% of previous dose if the rate of Hgb increase was > 1g/dL over a two week period OR the Hgb is increasing and approaching 12 g/dL. b. The ordered dose of Procrit is increased if the patient's Hgb has not increased by 1 g/dL over a 4 weeks period (See Dosage and Administration section) OR the patient's Hgb falls below 10 g/dL. c. An increase in dose does not occur more than once per month. The member is currently receiving ribavirin therapy that was initiated 20 weeks ago, or if beyond week 20 of ribavirin therapy, documentation submitted indicates a dosage reduction of ribavirin to 600 mg/day after week 20 but the member still became anemic. If the member had a normal vitamin B12 and Folate levels on the initial request OR had a low vitamin B12 and/or Folate level but has subsequently been placed on the appropriate supplementation then repeat vitamin B12 and Folate lab results are not needed until 1 year after the initial request. However if the patient was deficient in either vitamin B12 or Folate levels based on lab results from the initial request and is NOT receiving the appropriate supplementation then repeat vitamin B12 and Folate lab results must be submitted dated within 30 days of the request. If the member is iron deficient (ferritin concentration <100 ng/mL and/or percentage transferrin saturation < 20%), the member is in the process of receiving either oral or IV iron supplementation or the treatment plan is to start iron therapy. Procrit ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section)

· ·

· ·

If all of the above conditions are met, the request will be approved with a 3-month duration or up to the member completes Ribavirin therapy (24-48 weeks of treatment), if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section VI: PA Criteria for Approval for Treatment of Other Medically Acceptable Indications Place the patient into one of the following: - Procrit treatment initial request (Part A) - Reauthorization of Procrit® (Part B)

Part A: Procrit treatment initial request · · · · · Documentation was forwarded indicating the medication (including dose) was prescribed or recommended by a hematologist or a specialist in the respective disease state associated anemia. The member has a hemoglobin level < 11 g/dL OR if the member is new to the health plan and was receiving Procrit at the previous health plan the member has a documented (submitted lab result dated within 30 days of request) hemoglobin <12 g/dL Procrit is ordered be administered 2 to 3 times a week unless the patient has a medical reason for only receiving the medication on a once weekly basis If the member has low vitamin B12 levels and/or Folate levels then documentation submitted that indicates the member is or will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated. If the member is iron deficient (ferritin concentration <100 ng/mL and/or percentage transferrin saturation < 20%), the member is in the process of receiving either oral or IV iron supplementation (>200 mg elemental iron orally daily or periodic IV supplementation) or the treatment plan is to start iron therapy and then have the percentage transferrin saturation and ferritin levels monitored. The member has had a documented treatment failure at optimal doses of Aranesp and/or intolerance to Aranesp, and/or some other documented clinically significant reason for not using Aranesp to treat their anemia. Based on compendia and standard of care clinical guidelines, the Procrit ordered dose is consistent with approvable dosing guidelines for the medically acceptable indication being treated. (See Below - Dose and Administration section.

· ·

If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/mL and the transferrin saturation are > 20-55%) and not vitamin B-12 deficient and not folate deficient, OR a temporary supply of up to 1 month may be authorized if the member is functionally iron deficient (ferritin concentration < 100 ng/mL and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Reauthorization Criteria for Procrit · If the member has been receiving therapy and their hemoglobin is < 11 g/dL(submitted lab result dated within 30 days of request), OR if hemoglobin (submitted lab result dated within 30 days of request) is > 11g/dL < 12 g/dL & one of the following apply: a. The ordered dose of Procrit is reduced by 25% of previous dose if the rate of Hgb increase was > 1g/dL over a two week period OR the Hgb is increasing and approaching 12 g/dL. b. The ordered dose of Procrit is increased by 25% of the previous dose if the patient's Hgb has not increased by 1 g/dL over a 4 weeks period (See Dosage and Administration section) OR the patient's Hgb falls below 10 g/dL. c. An increase in dose does not occur more than once per month. Based on compendia and standard of care clinical guidelines, the Procrit ordered dose is consistent with approvable dosing guidelines for the medically acceptable indication being treated. (See Below - Dose and Administration section. If the member had a normal vitamin B12 and Folate levels on the initial request OR had a low vitamin B12 and/or Folate level but has subsequently been placed on the appropriate supplementation then repeat vitamin B12 and Folate lab results are not needed until 1 year after the initial request. However if the patient was deficient in either vitamin B12 or Folate levels based on lab results from the initial request and is NOT receiving the appropriate supplementation then repeat vitamin B12 and Folate lab results must be submitted dated within 30 days of the request. If the member is iron deficient (ferritin concentration <100 ng/mL and/or percentage transferrin saturation < 20%), the member is in the process of receiving either oral or IV iron supplementation or the treatment plan is to start iron therapy.

· ·

·

If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/mL and the transferrin saturation are > 20-55%) OR a

temporary supply of up to 1 month may be authorized if the member is functionally iron deficient (ferritin concentration < 100 ng/mL and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. FDA INDICATIONS: · Treatment of anemia of chronic renal failure patients · Treatment of anemia in Zidovudine-treated HIV-infected patients · Treatment of anemia due to the effect of concomitantly administered chemotherapy based on studies that have shown reduction in the need for RBC transfusions in patients with metastatic, non-myeloid malignancies receiving chemotherapy for a minimum of 2 months. o Procrit is not indicated for use in patient receiving hormonal agents, therapeutic biologic products, or radiotherapy unless receiving concomitant myelosuppressive chemotherapy o Procrit is not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is sure due to the absence of studies that adequately characterize the impart of Procrit on progression-free and overall survival o Procrit is not indicated for the treatment of anemia in cancer patients due to other factors such as iron or folate deficiencies, hemolysis, or gastrointestinal bleeding o Procrit use has not been demonstrated in controlled clinical trials to improve symptoms of anemia, quality of life, fatigue, or patient well-being · Treatment of anemic patients (Hgb > 10 to < 13 g/dL) who are at high risk for perioperative blood loss form elective, noncardiac, nonvascular surgery to reduce the need for allogeneic blood transfusions DOSAGE AND ADMINISTRATION: A. Pre-Dialysis CKD (Chronic Kidney Disease) patients: Therapeutic Guidelines in CRF Patients for Epoetin Alfa Starting dose Subcutaneous or Intravenous administration Maximum dose ­ (with normal Iron stores) Subcutaneous administration 300 units/kg/week 80 ­ 120 units/kg/week (typically 6,000 units/week)

Usual maintenance dose for Pre-dialysis CRF patients **Doses greater than maximum doses require hematologist consultation and recommendation. Reduce dose 25% when:

75 to 150 units/kg/week to maintain Hgb 10-12 g/dL

Dose should be temporarily withheld when

Increase dose up to 25% of previous dose if:

1). Hemoglobin approaches12 g/dL OR 2). Hemoglobin increases by more than 1.0 g/dL in 2-week period Hemoglobin exceeds 12 g/dL and until hemoglobin falls to 11 g/dL. Therapy should be reinitiated at a dose approximately 25% below the previous dose. 1) Hemoglobin is < 10 g/dl and has not increase by 1g/dL over a 4 week period OR 2) Hemoglobin decreases below 10 g/dl AND 3) Dosage increases should occur only after treating and/or ruling out functional iron deficiency anemia (TSAT <20% and Ferritin <100 ng/mL)

Maintenance dose

Suggested target Hemoglobin

Individualize to achieve and maintain the lowest Hgb level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dL. <12 g/dL or lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dL

B. Zidovudine-treated, HIV-infected patients: Therapeutic Guidelines in Zidovudine-treated, HIV-infected patients for Epoetin Alfa: Starting dose Subcutaneous or Intravenous administration Maximum dose ­ (with normal Iron stores) Subcutaneous or Intravenous administration *Doses greater than maximum doses require hematologist consultation and recommendation.* Reduce dose 25% when: 300 units/kg three times a week 100 units/kg three times a week

Dose should be temporarily withheld when

Increase dose up to 25% of previous dose if:

Maintenance dose Suggested target Hemoglobin

1). Hemoglobin approaches12 g/dL OR 2). Hemoglobin increases by more than 1.0 g/dL in 2-week period Hemoglobin exceeds 12 g/dL and until hemoglobin falls to 11 g/dL. Therapy should be reinitiated at a dose approximately 25% below the previous dose. 4) Hemoglobin is < 10 g/dl and has not increased by 1g/dL over a 4 week period OR 5) Hemoglobin decreases below 10 g/dl AND Dosage increases should occur only after treating and/or ruling out functional iron deficiency anemia (TSAT <20% and Ferritin <100 ng/mL) Individualize to achieve and maintain the lowest Hgb level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dL. <12 g/dL or lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dL

C. Anemia due to chemotherapy: Therapeutic Guidelines in Anemia due to Chemotherapy for Epoetin Alfa: Starting dose Subcutaneous administration for adult patients: Initial administration for pediatric patients Maximum dose ­ (with normal Iron stores) 150 units/kg three times a week or 40,000 units weekly 600 units/kg (maximum 40,000 units) intravenously weekly For adult patients 60,000 units weekly or 300 units/kg three times week SC For pediatric patients 900 units/kg (maximum 60,000 units) IV **Doses greater than maximum doses require hematologist

Reduce dose 25% when:

Dose should be temporarily withheld when

Therapy should be discontinued when: Increase dose up to: · For adult patients 60,000 units weekly OR 300 units/kg three times a week · For pediatric patients 900 units/kg (maximum 60,000 units) Maintenance dose Suggested target Hemoglobin

consultation and recommendation.** 1). Hemoglobin approaches 12 g/dL OR 2). Hemoglobin increases by more than 1.0 g/dL in 2-week period Hemoglobin exceeds 12 g/dL and until hemoglobin falls to 11 g/dL. Therapy should be reinitiated at a dose approximately 25% below the previous dose. The current course of chemotherapy has been completed. 1) If hemoglobin has not increased by greater than 1 g/dL after 4 weeks of therapy in the absence of a red blood cell transfusion AND 2) Dosage increases should occur only after treating and/or ruling out functional iron deficiency anemia (TSAT <20% and Ferritin <100 ng/mL) Individualize to achieve and maintain the lowest Hgb level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dL. <12 g/dL or lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dL

D. Guidelines for the use of Procrit in Surgery Patients: Prior to initiating treatment with Procrit, obtain a hemoglobin to establish that it is > 10 to <= 13 g/dL. The recommended dose is 300 U/kg/day SC for 10 days before surgery, on the day of surgery and for 4 days after surgery. An alternate dose schedule is 600 U/kg SC in once weekly doses (21, 14 and 7 days before surgery) plus a fourth dose on the day of surgery. All patients should receive adequate iron supplementation. Initiate iron supplementation no later than the beginning of treatment with Procrit and continue throughout the course of therapy. Deep venous thrombosis prophylaxis should be strongly considered. E. Guidelines for the use of Epoetin Alfa for Ribavirin Induced Anemia Initial therapy Studies using Procrit to treat ribavirin induced anemia typically used a 40,000 unit once per week. Based on the National Comprehensive Cancer Network guidelines, Procrit 40,000 units weekly is equivalent to 30,000 units per week if 30,000 units are divided into10,000 units to be administered 3 times over one week.. Therefore, approvable Procrit initial total weekly doses should not exceed 30,000 units/week administered in 2-3 divided doses over one week (i.e. 10,000 units three times weekly or 15,000 units in prefilled syringes twice weekly). Procrit 40,000 units once weekly will be approved if the member has a medical reason for not being able to receive Procrit 30,000 units/week divided evenly into 2-3 doses over one week. Length of therapy Medication should only be approved while the member is within the first 20 weeks of receiving Ribavirin and Interferon therapy to treat their Hepatitis C infection. If the member is to receive Interferon and Ribavirin therapy for greater than 20 weeks because they eradicated the HCV virus, the dose of Ribavirin at that time should be reduced to 600 mg/day, and if the member becomes anemic, then Procrit maybe reauthorized to treat the members anemia in order for the member to stay on 600 mg of Ribavirin a day. Dosage adjustments: o Decrease dose by 25% when: Hgb increases by > 1.0 g/dL in a 2-week period Or If the Hgb is increasing and approaching 12 g/dL. o Temporarily hold dose when: Hgb exceeds 12 g/dL and until Hgb falls below 11g/dL Therapy can be reinitiated at a dose approximately 25% below the previous dose

o

o

Increase dose by 25%, if the member's Hgb does not increase 1 g/dL after 4 weeks of therapy as long as the member is not iron, vitamin B12 and folate deficient, and after member's ribavirin dose was reduced to 600 mg /day. Target Hgb: <12 g/dL or lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dL

F. Other Medically Acceptable Indications Dosing Guidelines: · Based on the medical compendia (Drug Points, Micro Medex, AHFS) and standard of care clinical guidelines, the dose is appropriate for the medically acceptable indication being treated, · Dosage adjustments: o Decrease dose by 25% when: Hgb increases by > 1.0 g/dL in a 2-week period Or If the Hgb is increasing and approaching 12 g/dL. o Temporarily hold dose when: Hgb exceeds 12 g/dL and until Hgb falls below 11g/dL Therapy can be reinitiated at a dose approximately 25% below the previous dose o Increase dose by 25%, if the member's Hgb does not increase by 1 g/dL after 4 weeks of therapy as long as the member is not iron, vitamin B12 and folate deficient. · Target Hgb: <12 g/dL or lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dL Conversion from epoetin alfa (Procrit) to darbepoetin: Estimate the starting weekly dose of darbepoetin based on the weekly epoetin alfa dose at the time of substitution. Titrate doses to maintain the target hemoglobin. Because of the longer serum half-life, administer darbepoetin less frequently than epoetin alfa. Administer once a week if member was receiving epoetin alfa 2 to 3 times weekly. Administer darbepoetin once every 2 weeks if the member was receiving epoetin alfa once per week. Maintain the route of administration (IV or SC). Estimated Darbepoetin Starting Doses Based on Previous Epoetin Alfa Dose Previous weekly epoetin alfa dose Every 2 weeks or weekly starting darbepoetin dose (units/week) (mcg) < 2499 12.5 every 2 weeks 2500 to 4999 25 every 2 weeks 5000 to 10,999 25 once weekly 11,000 to 17,999 40 once weekly 18,000 to 33,999 60 once weekly 34,000 to 89,999 100 once weekly 90,000 200 once weekly TABLE 1 The Definition of Chronic Kidney Disease The KDOQI defines Chronic Kidney Disease with two independent criteria: Kidney damage for > 3 months as defined by structural or functional abnormalities of the kidney, with or 1. without decreased GFR, manifest by either: · Pathological abnormalities OR · Markers of kidney damage, including abnormalities in the composition of the blood or urine, or abnormalities in imaging tests GFR < 60 ml/min/1.73m2 for >3 months with or without kidney damage 2.

National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification. Am J Kidney Dis 39: S1S266, 2002 (suppl 1). REFERENCES:

1. 2. 3. 4.

5. 6. 7. 8. 9.

National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease, 2000. Am J Kidney Dis 37:S182-S238, 2001 (suppl 1) National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification. Am J Kidney Dis 39: S1-S266, 2002 (suppl 1). Available from URL: http://www.kidney.org/professionals/kdoqi/gfr_calculator.cfm. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Cancer and Treatment-Related Anemia. Version 2.2007. Rizzo JD, Lichtin AE, Woolf SH, Seidenfeld J, Bennett CL, Cella D, Djulbegovic B, Goode MJ, Jakubowski AA, Lee SJ, Miller CB, Rarick MU, Regan DH, Browman GP, Gordon MS. Use of Epoetin in Patients With Cancer: Evidence-Based Clinical Practice Guidelines of the American Society of Clinical Oncology and the American Society of Hematology. Journal of Clinical Oncology, Vol 20, No. 19 (October 1), 2002: pp 4083-4107. Available from URL: http://www.asco.org/asco/downloads/guidelines/2002EPO.pdf Lichtin A. The ASH/ASCO clinical guidelines on the use of erythropoietin. Best Practice & Research Clinical Haematology. 2005; 18(3):433-438. HIV and AIDS Anemia and Fatigue. [resource on World Wide Web]. URL: http://www.hivandhepatitis.com/recent/lipo/071902_anemia.html#who Int J Antimicrob Ag 1997; 8:189 Ortho Biotech Inc. Procrit® (Epoetin Alfa). Prescribing Information, 8/2008. Volberding PA, Levine AM, Dietrich D, et al. Anemia in HIV Infection: Clinical Impact and Evidence-Based Management Strategies. Clinical Infectious Diseases 2004;38:1459-68

10.

Aranesp® (darbepoetin alfa). Prescribing Information, Amgen. 11/2007. 11. Revision/ Rigsby M, Burgess J, and Davey V et al. VA Treatment Recommendations: Patients with Chronic Hepatitis C. Federal Practitioner Supplement. 2003; Vol 20 Suppl. 5: 1-32. 12. Shiffman M, DiBisceglie A, and Lindsay K et al. Peginterferon Alfa-2a and Ribavirin in Patients with Chronic Hepatitis C Who Have Failed Prior Treatment. Gastroenterology. 2004; Vol 126: 1015-1023. 13. http://www.chemocare.com/bio/list_by_acronym.asp?acronyn

Review Date: 5/2009 Associated Policy: Prior Authorization of Medications 236.200

NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA PULMONARY ARTERIAL HYPERTENSION (PAH) TREATMENT Adcirca® (Tadalafil): Tablets 20 mg LetairisTM (Ambrisentan): Tablets 5 mg, 10 mg ® Revatio (Sildenafil): Tablets 20 mg Tracleer® (Bosentan): Tablets 62.5 mg, 125 mg ® Viagra (Sildenafil): Tablets 25 mg, 50 mg, 100 mg (for use in pediatric compounding only) PREFERRED PRODUCTS: Letairis, Adcirca & Revatio Preferred (with prior authorization). Viagra, when used in compounding for pediatric patients (<9 y/o), will process at the point of sale. PA CRITERIA FOR INITIAL APPROVAL: · Documentation of a confirmed diagnosis of pulmonary arterial hypertension (PAH) World Health Group (WHO Group I). See Box 1. AND · Medication is being used for an FDA approved functional class (See Box 2 & Box 3). o **Please Note** For newborn and pediatric patients < 9 years old, Viagra tablets used in pediatric compounding for the treatment of pulmonary arterial hypertension will process at the point of sale. THE USE OF VIAGRA FOR ALL OTHER PATIENTS, INDICATIONS, OR SITUATIONS IS NOT ACCEPTABLE AND SHOULD NOT BE APPROVED. AND · If the provider is requesting combination therapy with two agents then documentation must be submitted of an adequate trial (> 3 months) with monotherapy, documentation that the patient has been compliant with the single agent, and documentation that the patient has clinically deteriorated (e.g. worsening of the symptoms of dyspnoea or fatigue, decline in functional class by at least one class) while on monotherapy. If all of the above conditions are met, the request for all oral treatment will be approved for up to a 12 month duration; if all of the above criteria are not met the request is referred to a Medical Director for medical necessity review. Box 1 WHO Group Classification of PAH Group I. Pulmonary arterial hypertension (PAH) · Idiopathic (IPAH) · Familial (FPAH) · Associated with (APAH): o Connective tissue disease (systemic sclerosis (scleroderma) & systemic lupus erythematosus (SLE)) o Congenital systemic ­to- pulmonary shunts o Portal hypertension o HIV infection o Drugs and toxins o Other (thyroid disorders glycogen storage disease, Gaucher's disease, hereditary hemorrhagic telangiectasia, haemoglobinapathies, myeloproliferative disorders, splenectomy) · Associated with significant venous or capillary involvement o Pulmonary veno-occlusive disease (PVOD) o Pulmonary capillary haemangiomatosis (PCH) · Persistent pulmonary hypertension of the newborn (PPHN) Group II. Pulmonary hypertension associated with left heart diseases Group III. Pulmonary hypertension associated with respiratory diseases and/or hypoxemia (including chronic obstructive pulmonary disease. Group IV. Pulmonary hypertension due to chronic thrombotic and/or embolic disease Group V. Miscellaneous group e.g. sarcoidosis, histiocytosis X, and lymphangiomatosis Box 2 NYHA & WHO Functional Classifications NYHA Functional Classification Class I: No symptoms with ordinary physical activity. Class II: Symptoms with ordinary activity. Slight limitation of activity. Class III: Symptoms with less than ordinary activity. Marked limitation of activity. Class IV: Symptoms with any activity or even at rest. WHO Functional Assessment Classification Class I: Patients with PH but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or near syncope. Class II: Patients with PH resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope. Class III: Patients with PH resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope. Class IV: Patients with PH with inability to carry out any physical activity without symptoms. These patients manifest signs of right-heart failure. Dyspnea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity.

Box 3 PAH Medications Functional Class Indications Drug FDA Approved Functional Class of Symptoms Adcirca® WHO Group I Tracleer® WHO Class III and IV Revatio ® WHO Group I LetairisTM WHO Class II and III FDA INDICATION: Adcirca®: Indicated for the treatment of pulmonary arterial hypertension (WHO Group I) to improve exercise ability. LetairisTM: Indicated for the treatment of pulmonary arterial hypertension (WHO Group I) in patients with WHO class II or III symptoms to improve exercise capacity and delay clinical worsening. Revatio ®: Indicated for the treatment of pulmonary arterial hypertension (WHO Group I) to improve exercise ability and delay clinical worsening. The delay in clinical worsening was demonstrated when Revatio was added to background Flolan therapy.. Tracleer®: Indicated for the treatment of pulmonary arterial hypertension (WHO Group 1) in patients with WHO Class III or IV symptoms, to improve exercise ability and decrease the rate of clinical worsening. DOSAGE AND ADMINISTRATION: Adcirca®: The recommended dose is 40 mg (two 20 mg tablets) taken once daily with or without food. Dividing the dose (40mg) over the course of the day is not recommended. LetairisTM: Initiate treatment at 5mg once daily with or without food, and consider increasing the dose to 10mg once daily if 5mg is tolerated. Revatio ®: The recommended dose is 20mg t.i.d. taken approximately 4-6 hours apart. Treatment with doses higher than 20mg t.i.d. is not recommended. Tracleer : Initial dose 62.5mg b.i.d. for 4 weeks and then increased to a maintenance dose of 125mg b.i.d. Doses above 125mg b.i.d. did not appear to confer additional benefit to offset the increased risk of liver injury. REFERENCES: 1. Adcirca® Prescribing Information. Eli Lilly and Company. May 2009 2. Tracleer® Prescribing Information. Actelion Pharmaceuticals US, Inc. March 2009. ® 3. Revatio Prescribing Information. Pfizer Labs. May 2009. TM 4. Letairis Prescribing Information. Gilead Sciences, Inc. August 2009. 5. Badesch DB, Abman SH, Simonneau G, et al. Medical Therapy for Pulmonary Arterial Hypertension: Updated ACCP Evidence- Based Clinical Practice Guidelines. Chest 2007; 131: 1917-1928. 6. Humbert M, Sitbon O, Simonneau G. Treatment of Pulmonary Arterial Hypertension. N Engl J Med 2004; 351:1425-36. 7. Nauser TD, Stites SW. Diagnosis and Treatment of Pulmonary Hypertension. Am Fam Physician 2001; 63: 1789-98, 1800. Revision/Review Date: 8/2011 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

®

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA RITUXAN® (rituximab): 100mg/ml in 10 and 50ml vials PA CRITERIA FOR APPROVAL FOR USE IN RHEUMATOID ARTHRITIS: · The medication is being recommended and prescribed by a rheumatologist. · The patient is an adult (18 y/o) and has a documented clinical diagnosis of rheumatoid arthritis. · The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates, doses of 3 months or more of therapy) of methotrexate (at a maximum dose) AND then leflunomide (Arava®) and/or triple combination therapy (sulfasalazine, hydroxychloroquine, and methotrexate), and/or has another documented medical reason (intolerance, hypersensitivity, etc) for not utilizing any of these therapies to manage their medical condition. · The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates, doses) of etanercept (Enbrel®) and/or adalimumab (Humira®) and/or has another medical reason (intolerance, hypersensitivity, etc) for not taking any of these therapies to manage their medical condition. · Documentation indicating that Rituxan is being used concurrently with methotrexate. · Rituxan is being prescribed at an FDA approved dosage. If all of the above conditions are met, the request will be approved for up to a 1 month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR RE-AUTHORIZATION FOR USE IN RHEUMATOID ARTHRITIS · The member has been receiving Rituxan and documentation is provided that a rheumatologist has reevaluated the member and recommends continuation of therapy. · Documentation was provided indicating that the patient had clinical benefit from receiving Rituxan therapy. · At least 24 weeks (6 months) has elapsed since the previous course of Rituxan therapy. · Documentation indicating that Rituxan is being used concurrently with methotrexate. · Rituxan is being prescribed at an FDA approved dosage. If all of the above conditions are met, the request will be approved for up to a 1 month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR INITIAL APPROVAL FOR USE IN NON-HODGKIN'S LYMPHOMA (NHL): · The medication is being recommended and prescribed by an oncologist. · Documentation that the patient has CD20-positive B-cell NHL (from a Hematopathology review of all the patient's slides with at least on paraffin block representative of the tumor, lymph node diagnosis and/or bone marrow biopsy with cell surface marker analysis by flow cytometry) · Rituxan is being prescribed at a dose that is within FDA approved guidelines and/or is supported by the medical compendium as defined by the Social Security Act and/or the National Comprehensive Cancer Network (NCCN) or American Society of Clinical Oncology (ASCO) standard of care guidelines. If all of the above conditions are met, the request will be approved for up to a 3 month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested.

PA CRITERIA FOR RE-AUTHORIZATION FOR USE IN NON-HODGKIN'S LYMPHOMA (NHL) · The medication is being recommended and prescribed by an oncologist. · Rituxan® is being prescribed at a dose that is within FDA approved guidelines and/or is supported by the medical compendium as defined by the Social Security Act and/or per the NCCN or ASCO standard of care guidelines. If all of the above conditions are met, the request will be approved for up to a 3 month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR INITIAL AUTHORIZATION FOR USE IN OTHER MEDICALLY ACCEPTED INDICATIONS · The medication is prescribed for a non-FDA approved indication but is considered to be a medically accepted use of the medication per the medical compendia (Micromedex, American Hospital Formulary Service (AHFS), Drug Points, Drug Package Insert) as defined in the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO) or the American Academy of Pediatrics (AAP) standard of care guidelines. · The medication is prescribed at a medically accepted dose per the medical compendia as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO) or the American Academy of Pediatrics (AAP) standard of care guidelines. · The medication is recommended and prescribed a specialist in the field to treat the member's respective medical condition. · Documentation was submitted indicating that the member has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates, doses of medications) of all first line medical therapies as recommended by the medical compendia and standard care guidelines and/or has another documented medical reason (e.g. intolerance, contraindications, etc.) for not receiving or trying all first line medical treatment(s). If all of the above conditions are met, the request will be approved for up to a 3 month duration. If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR RE-AUTHORIZATION FOR USE IN OTHER MEDICALLY ACCEPTED INDICATIONS · Documentation that the medication is recommended or prescribed by a specialist for the respective treated disease state and is being prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, American Hospital Formulary Service (AHFS), Drug Points , Drug Package Insert) as defined in the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO) or the American Academy of Pediatrics (AAP) standard of care guidelines. · Documentation from medical chart was submitted indicating that the member has significantly clinically benefited from the medication. If all of the above conditions are met, the request will be approved for up to a 3 month duration, if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested.

FDA INDICATIONS: Rheumatoid arthritis (RA): In combination with methotrexate to reduce signs and symptoms in adult patients with moderately to severely active RA who have had inadequate response to 1 or more tumor necrosis factor (TNF) antagonist therapies Non-Hodgkin's Lymphoma (NHL): · Indicated for the treatment of patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-Cell, NHL · Indicated for the first-line treatment of follicular CD20-positive, B-cell NHL in combination with cyclophosphamide, doxorubicin and prednisone (CVP) chemotherapy. · Indicated for the first-line treatment of diffuse large B-cell, CD20 positive, NHL in patients with stable disease or who achieve a partial or complete response following first line treatment with CVP chemotherapy. · Indicated for the first line treatment of diffuse large B-cell CD20 positive, NHL in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or other anathracycline-based chemotherapy regimens. NON-FDA MEDICALLY ACCEPTED INDICATIONS (includes but not limited to): Marginal zone lymphoma, gastric MALT lymphoma, non-gastric MALT lymphoma, splenic marginal zone lymphoma, mantle cell lymphoma, Burkitt's lymphoma, lymphoblastic lymphoma, AIDS-related B-cell lymphoma, autoimmune hemolytic anemia, chronic lymphoid leukemia (first line, relapsed or refractory), graft-versus-host disease (chronic steroid-refractory), Waldenstrom's macroglobulinemia, treatment of systemic autoimmune diseases (other than rheumatoid arthritis), immune or idiopathic thrombocytopenic purpura and polymorphic posttransplantation lymphoproliferative disorder. This is not a comprehensive list as updated medical evidence is continually being published. DOSAGE AND ADMINISTRATION: Adult Patients with Rheumatoid Arthritis: 1000 mg IV followed by a second 1000 mg IV dose 2 weeks later; MAX: a total of 2 doses; used in combination with methotrexate. Premedication: administer a glucocorticoid 30 minutes prior to each infusion (such as methylprednisolone 100 mg IV or its equivalent). Adult Patients with Diffuse Large B-Cell, CD20-positive NHL: 375 mg/m² IV infusion on day 1 of each anthracycline-containing chemotherapy cycle, for up to 8 cycles. Adult Patients with NHL, receiving: as a component of ibritumomab tiuxetan therapeutic regimen: 250 mg/m² IV infusion within 4 hr prior to admini0stration of indium-111 ibritumomab tiuxetan, then 7-9 days later within 4 hr prior to administration of yttrium-90 ibritumomab tiuxetan. Adult Patients with Relapsed or Refractory, Low-grade or Follicular, CD20-positive, B-cell NHL: Single agent, 375 mg/m² IV infusion once weekly for 4 or 8 doses; may retreat with additional 4 doses on days 1,8,15 and 22 with progressive disease. Limited data for treatment beyond 2 courses. Non-Hodgkin's lymphoma for patients with previously untreated follicular CD20-positive, B-Cell: 375 mg/m2 IV infusion on day 1 of each cycle of CVP chemotherapy cycle, for up to 8 doses Rituxan should not be administered as an intravenous push or bolus.

WARNINGS: Fatal Infusion Reactions: Deaths within 24 hours of Rituxan infusion have been reported. These fatal reactions followed an infusion reaction complex which included hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation or cardiogenic shock. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Patients who develop severe infusion reactions should have Rituxan infusion discontinued and receive medical treatment. Tumor Lysis Syndrome (TLS): Acute renal failure requiring dialysis with instances of fatal outcome has been reported in the setting of TLS following treatment with Rituxan. Severe mucocutaneous reactions, some with fatal outcome, have been reported in association with Rituximab treatment

REFERENCE: 1. Emery P, Fleischmann R, Filipowicz-Sosnowska A, et. al. The Efficacy and Safety of Rituximab in Patients with Active Rheumatoid Arthritis Despite Methotrexate Treatment: Results of a Phase IIb Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Trial. Arthritis & Rheumatism; 2006 54(5): 1390-1400. 2. Bokarewa M, Lindholm C, Zendjanchi K, et. al. Efficacy of Anti-CD20 Treatment in Patients with Rheumatoid Arthritis Resistant to a Combination of Methotrexate/Anti-TNF Therapy. Scandinavian Journal of Immunology 2007; 66: 476-83. 3. Lexicomp 2007 4. ASHS 2006-07 5. Micromedex 2007 6. Manufacturer package insert for Rituxan® Genentech, Inc. 8/2007. 7. NCCN Clinical Practice Guidelines in OncologyTM: Non-Hodgkin's Lymphomas; V.2.2007 Update. 8. Cohen SB, Emery P, Greenwald MW, et al. Rituximab for Rheumatoid Arthritis Refractory to Anti-Tumor Necrosis Factor Therapy: Results of a Multicenter Randomized, Double-Blind, Placebo-Controlled, Phase III Trial Evaluating Primary Efficacy and Safety at Twenty-Four Weeks. Arthritis & Rheumatism; 2006 54(9): 2793-2806.

Revision/Review Date: 5/2009 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA SYNAGIS®(palivizumab): 50mg vial, 100mg vial PA CRITERIA FOR APPROVAL FOR FDA APPROVED INDICATIONS: · The request for Synagis has all the following information submitted with the request: documentation of chronological age, gestational age, current weight, dose of medication and pertinent medical risk factors. · If the child's current chronological age is less than 2 years of age at the beginning of Respiratory Syncytial Virus (RSV) season (November 1st), and the child has significant medical risk factors (chronic lung disease of prematurity (CLD) a.k.a. bronchopulmonary dysplasia (BPD)) requiring medical treatment either (i.e. supplemental oxygen, bronchodilator, diuretic or chronic corticosteroid therapy) within 6 months of the start of or during the current RSV season, severe immunodeficiencies/immunosuppression (see Table 3), or significant cardiac disease (i.e. those that require medication to control CHF, moderate to severe pulmonary hypertension or cyanotic heart disease) (see Table 1 & 2) that could be complicated by pulmonary disease. · If the child was born prematurely with a gestational age of 28 weeks & 6 days or less, and the child's current chronological age is less than or equal to 1 year at the beginning of RSV season (November 1st). · If he child was born prematurely with a gestational age between 29 and 31 weeks & 6 days and the child's current chronological age is less than or equal to 6 months at the beginning of RSV season (November 1st) · If the child was born prematurely with a gestational age of less than 35 weeks (i.e. 34 weeks & 6 days) and the child's current chronological age is less than or equal to 1 year at the beginning of RSV season (November 1st) and the child was born with a congenital abnormality of the airway or neuromuscular disease. · If the child has a gestational age of 32 till less than 35 weeks (i.e. 34 weeks & 6 days) and the child's current chronological age is less than 3 months at the beginning of RSV season (November 1st) and the child has at least 1 of the following risk factors: sibling(s) younger than 5 years old, attends child care (defines as a home or facility where care is provided for any number of infants or young toddlers in the child care facility), OR exposure to one of the environmental air pollutants listed in Table 4.**IMPORTANT NOTE** These patients are only eligible to be approved a quantity of Synagis needed to treat the patient until he/she is 3 months (90 days) old OR until the end of March (a maximum of 3 doses), whichever is first. · The request is for Synagis to be administered any time, but no more than once per 30 days, from November 1st through the end of March, unless the prescribing physician provides epidemiology data that suggests RSV prophylaxis should start before November 1st and/or continue beyond the end of March. · The prescribed dose of Synagis is in accordance with the FDA dosing recommendations. If the above conditions are met, the request will be approved with a quantity sufficient dependent on the patient's chronological age, gestational age, and/or clinical situation. For patients with a gestational age between 32 till less than 35 weeks (without any significant medical conditions) they will only be approved a maximum quantity of 3 doses. All other patients will be approved with a quantity sufficient to provide coverage from (November 1st). through March 31st (a maximum quantity of 5 doses). If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. FDA INDICATIONS: Synagis is indicated for the prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in pediatric patients at high risk of RSV disease. DOSAGE AND ADMINISTRATION: The recommended dose of Synagis is 15 mg/kg of body weight. Patients, including those who develop a RSV infection, should receive monthly doses throughout the RSV season. The first dose should be administered prior to commencement of the RSV season. **MAXIMUM APPROVABLE DOSES** 1. Patients born between 32 till less than 35 weeks of gestation, and without any significant medical conditions, will only receive Synagis treatment until they are 3 months (90 days) old (a maximum of 3 doses). Treatment with Synagis is not recommended for these patients past the age of 3 months old and, therefore, will not be approved. 2. For all other patients, they will only receive Synagis treatment for a maximum of 5 doses. There are no valid clinical reasons for a 6th dose of Synagis and, therefore, all requests for a 6th dose will be denied.

Table 1. EXAMPLES OF SIGNIFICANT AND APPROVABLE CARDIAC CONDITIONS Examples of significant hemodynamic cyanotic congenital heart disease: Tetralogy of Fallot, Transportation of the great vessels, Ebstein's anomally, Tricuspid atresia, Total anomalous pulmonary venous return, Truncus arteriosus, Hypoplastic left heart syndrome Table 2. NON-APPROVABLE CARDIAC CONDITIONS Insignificant hemodynamic heart disease (and therefore Indications in which patients are NOT at an increased are NOT approvable indications): risk for RSV (and therefore are NOT approvable indications) Secundum atrial septal defect, small ventricular septal · Lesions adequately corrected by surgery (unless the defect, pulmonic stenosis, uncomplicated aortic stenosis, patient continues to require medications for CHF) mild coarctation of the aorta, patent ductus arteriosus · Mild cardiomyopathy who are NOT receiving medical therapy Table 3. EXAMPLES OF SEVERE IMMUNODEFICIENCIES/IMMUNOSUPPRESSION: Advanced Acquired Immunodeficieny Syndrome (AIDS), Transplant, Chemotherapy, Severe Combined Immunodeficiency (SCID) Table 4. APPROVABLE ENVIRONMENTAL POLLUTANTS Paper mill, coal burning power plants, wood burning stoves REFERENCES: 1. American Academy of Pediatrics: Committee on Infectious Diseases and Committee on Fetus and Newborn, Prevention of respiratory syncytial virus infections: Indications for the use of Palivizumab and update on the use of RSV-IGIV. PEDIATRICS November 1998; Vol.102 No. 5:1211-1215. 2. American Academy of Pediatrics. [chapter title]. In: Pickering LK, Baker CJ, Long SS, McMillan JA, eds. Red Book: 2009 Report of the Committee on Infectious Diseases. American Academy of Pediatrics; 2009: 562-568. 3. Facts and Comparisons, St. Louis, 2005 eFacts CliniSphere Version ISBN 1-57439-036-8. 4. NREVSS: RSV Surveillance: Trends in the U.S. April 14, 2008. Available at : http://www.cdc.gov/surveillance/nrevss/index.htm. Accessed April 2008. 6. Update: Respiratory Syncytial Virus Activity--United States, 1995-96 Season. December 8, 1995: 44(48); 900-902. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/00039753.htm. Accessed April 2008. 5. RSV Surveillance 2005-2006: A Nationwide Hospital and Office-Based RSV Epidemiology Pilot Study. Pan American Society for clinical Virology. March 2007: 34; 1-9. 6. Synagis® Prescribing Information. MedImmune, LLC. March 2009 Revision/Review Date: 9/2011 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA TYKERBTM (lapatinib): Tablets: 250 mg STATUS: Non-Preferred

PA CRITERIA FOR APPROVAL FOR BREAST CANCER: · Diagnosis of advance and/or metastatic breast cancer. AND · Documentation that the patient is human epidermal receptor type 2 (HER2) positive. AND · Documentation that the patient is estrogen receptor and progesterone receptor negative or refractory to hormonal treatment or has symptomatic visceral disease. AND · Documentation (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) that the patient has had an adequate trial (including dates and doses) at therapeutic doses with an anthracycline (i.e. Doxorubicin or Epirubicin) a taxane (i.e. Docetaxel or Paclitaxel) and Herceptin® (trastuzumab). AND · Documentation of concurrent use of Xeloda® (capecitabine). AND · The medication is being prescribed at a dose that is within FDA approved guidelines and/or is supported by the medical compendium as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or American Society of Clinical Oncology (ASCO) standard of care guidelines. If the above conditions are met, the request will be approved for a duration of 6 months; if the above conditions are not met, the request will be referred to a Pharmacist for medical necessity review. PA CRITERIA FOR RE-AUTHORIZATION FOR BREAST CANCER: · The medication is being prescribed at an FDA approved dosage. AND · Documentation from medical charts indicating continuation of therapy due to the member significantly clinically benefited from the medication. AND · If the request is for a dosage increase of greater than 1,250mg/day, documentation that Tykerb® is being coadministered with a CYP3A4 inducer and rationale for why another medication could not be used to manage their medical condition. If the above conditions are met, the request will be approved for a duration of 6 months; if the above conditions are not met, the request will be referred to a Pharmacist for medical necessity review. PA CRITERIA FOR AUTHORIZATION FOR USE IN A NON-FDA APPROVED MEDICALLY ACCEPTED INDICATION: · · The medication is recommended and prescribed by a specialist in the field to treat the member's respective medical condition. The medication is prescribed for a non-FDA approved indication but is considered to be a medically accepted use of the medication per the medical compendia (i.e. Micromedex, DrugPoints [formerly known as USPDI] and AHFS drug information) as defined by the

·

·

Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or the American Society of Clinical Oncology (ASCO). Documentation was submitted indicating that the member has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates, doses of medications) of all first line medical therapies as recommended by the medical compendia and standard care guidelines and/or has another documented medical reason (i.e. intolerance, contraindications, etc.) for not receiving or trying all first line medical treatment(s). The medication is prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, DrugPoints [formerly known as USPDI] and AHFS drug information) as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or the American Society of Clinical Oncology (ASCO).

If all of the above conditions are met, the request will be approved for up to a 6 month duration. If all of the above criteria are not met, the request is referred to a Pharmacist for medical necessity review. PA CRITERIA FOR RE-AUTHORIZATION FOR USE IN A NON-FDA APPROVED MEDICALLY ACCEPTED INDICATION: · The medication is recommended and prescribed by a specialist in the field to treat the member's respective medical condition. · The medication is being prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, DrugPoints [formerly known as USPDI] and AHFS drug information) as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or the American Society of Clinical Oncology (ASCO). · Documentation from medical charts indicating continuation of therapy due to the member significantly clinically benefited from the medication. · If the request is for a dosage increase of greater than 1,250mg/day then documentation that Tykerb® is being coadministered with a CYP3A4 inducer and rationale for why another medication could not be used to manage their medical condition. If all of the above conditions are met, the request will be approved for up to a 6 month duration. If all of the above criteria are not met, the request is referred to a Pharmacist for medical necessity review. FDA INDICATION: Breast Cancer: This combination is approved for the treatment of patients with advanced breast cancer whose tumors overexpress human epidermal receptor type 2 (HER2) and who have received prior treatment with an athracycline, a taxane, and traztuzumab. DOSAGE AND ADMINISTRATION: The recommended dosage of Tykerb® is 1250mg (5 tablets) given once daily on days 1 to 21 continuously in combination with Xeloda® 2,000mg/m2/day(given orally in two divided doses approximately 12 hours apart) on days 1 to 14 in a repeating 21 day cycle. Tykerb® should be taken at least 1 hour before or after meals. The dosage of Tykerb® should be given once daily; dividing the dosage in not recommend. Treatment should continue until disease progression or unacceptable toxicity occurs.

DOSAGE ADJUSTMENT Hepatic impairment: Severe hepatic impairment (Child-Pugh class C): consider a dose reduction to 750mg once daily. Cardiac events: Tykerb® should be discontinued in patients with a decreased left ventricular ejection fraction (LVEF) that is a Grade 2 of greater by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) and in patients with a LVEF that drops below the institution's lower limit of normal. Tykerb® may be restarted at a reduced dose (1,000 mg/day) after a minimum of 2 weeks if the LVEF recovers to normal and the patient is asymptomatic In renal impairment: Due to the minimal renal elimination (<2%), dosage adjustments for renal dysfunction may not be necessary. Due to concomitant use of CYP3A4 inhibitors/inducers: · Strong CYP3A4 inhibitors (i.e. azole antifungals, clarithromycin, nefazodone, protease inhibitors and telithromycin): An alternate medication for the CYP3A4 enzyme inhibitor should be investigated first, however if Tykerb® must be administered with a potent enzyme inhibitor then dose reductions are likely to be necessary. Consider reducing Tykerb® to 500mg once daily with careful monitoring. When a strong CYP3A4 inhibitor is discontinued, the provider should allow one week to elapse before titrating the dose upward. · CYP3A4 inducers (i.e. dexamethasone, phenytoin, carbamazepine, phenobarbital, rifamycins, and St. John's wart): An alternate medication for the CYP3A4 enzyme inducer should be investigated first, however if Tykerb® must be administered with a potent enzyme inducer then an increase in dose may be required. The dose may be increased up to 4500mg/day with carefully monitoring. When a strong CYP3A4 inducer is discontinued, the dose of Tykerb® should be reduced to the indicated dose REFERENCES: 1. NCCN Clinical Practice Guidelines in OncologyTM: Breast Cancer; V.2.2007. 2. Tykerb® Prescribing Information, GlaxoSmithKline Pharmaceutical, 2007. 3. Lexicomp® 2007. 4. Geyer CE, Forster J, Lindquist D, et. al. Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer. N Engl J Med 2006; 355:2733-43. Revision/Review Date: 8/2008 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Pharmacist review must override criteria when, in his/her professional judgment, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA TYSABRI® (natalizumab): 300mg/15mL single use vial PA CRITERIA FOR INITIAL AUTHORIZATION FOR USE IN MULTIPLE SCLEROSIS (MS): · Documentation submitted indicates that the member is an adult ( 18 y/o) and has a clinical diagnosis of a relapsing form of multiple sclerosis. · Clinical or diagnostic information was submitted that indicates that that patient has a documented (consistent with pharmacy claims data OR for new members to the health plan consistent with medical chart history) treatment failure (see Box 1 for definition of treatment failure) after receiving an adequate trial (including dates, doses of 6 months or more of each therapy) of interferon Beta- 1A (Rebif®) and glatiramer acetate (Copaxone®) or has a some other documented medical reason (intolerance, hypersensitivity, etc) for not utilizing all of these therapies for a minimum of 6 months each to manage their medical condition. · Documentation consistent with pharmacy claims data was submitted indicating the patient is not currently using any antineoplastic, immunosuppressant, or immunomodulating medications and does not have a history of progressive multifocal leukoencephalopathy (PML) and does not have a compromised immune system. · Documentation on request form indicates that the medication is prescribed by a neurologist who is authorized by the TOUCHTM program to prescribe TYSABRI® and that the patient is enrolled in the TOUCHTM program and has agreed to comply with the requirements for receiving TYSABRI®. · TYSABRI®is being prescribed at an FDA approved dosage. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR REAUTHORIZATION FOR USE IN MS: · Documentation was submitted indicating that the member is an adult ( 18 y/o) and has a current clinical diagnosis of a relapsing form of multiple sclerosis. · Diagnostic or clinical documentation was submitted (e.g. improved disease activity index, quality of life, blood work, radiographic evidence etc.) that indicates the member has significantly clinically benefited from receiving TYSABRI® therapy. · Documentation consistent with pharmacy claims data was submitted indicating the patient is not currently using any antineoplastic, immunosuppressant, or immunomodulating medications and does not have a history of progressive multifocal leukoencephalopathy (PML) and does not have a compromised immune system. · Documentation on request form indicates that the medication is prescribed by a neurologist who is authorized by the TOUCHTM program to prescribe TYSABRI® and that the patient is enrolled in the TOUCHTM program and has agreed to comply with the requirements for receiving TYSABRI®. · TYSABRI® is being prescribed at an FDA approved dosage If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR INITIAL APPROVAL FOR CROHN'S DISEASE: · The member is an adult ( 18 y/o) and has a documented clinical diagnosis of moderate to severely active Crohn's Disease · The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates and doses) at therapeutic doses or has some documented clinically significant medical reason for not receiving oral conventional therapy to manage their medical condition. · The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates and doses) with therapeutic doses of or has some documented clinically significant medical reason for not receiving Humira® (adalimumab) or Remicade® (infliximab). · Documentation on request form indicates that the medication is prescribed by a gastroenterologist who is authorized by the TOUCHTM program to prescribe TYSABRI® and that the patient is enrolled in the TOUCHTM program and has agreed to comply with the requirements for receiving TYSABRI®.

·

TYSABRI® is being prescribed by a gastroenterologist at an FDA approved dosage.

If all of the above conditions are met, the request will be approved for up to a 3-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR REAUTHORIZATION FOR USE IN CROHN'S DISEASE: · Documentation was submitted indicating that the member is an adult ( 18 y/o) and has a documented clinical diagnosis of moderate to severely active Crohn's Disease · Diagnostic or clinical documentation was submitted (e.g. improved disease activity index, quality of life, blood work, radiographic evidence etc.) that indicates the member has significantly clinically benefited from receiving TYSABRI® therapy. · For patients who where on chronic (continuously for > 3 months) oral corticosteroids prior to beginning treatment with TYSABRI®, documentation must be submitted that the patient has begun to taper off of the oral steroid treatment. For patients who are not able to completely taper off of oral corticosteroids within six months of starting TYSABRI® treatment, the treatment with TYSABRI® will be discontinued and no further authorization for this medication will be granted. · Documentation on request form indicates that the medication is prescribed by a gastroenterologist who is authorized by the TOUCHTM program to prescribe TYSABRI® and that the patient is enrolled in the TOUCHTM program and has agreed to comply with the requirements for receiving TYSABRI®. · TYSABRI® is being prescribed by a gastroenterologist at an FDA approved dosage. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR INITIAL AUTHORIZATION FOR USE IN OTHER MEDICALLY ACCEPTED INDICATIONS: · The medication is recommended and prescribed a specialist in the field to treat the member's respective medical condition. · The medication is prescribed for a medically accepted use per the medical compendia (i.e. Micromedex, DrugPoints, AHFS drug information) as defined by the Social Security Act. · Documentation was submitted indicating that the member has a documented (consistent with pharmacy claims data) adequate trial (including dates, doses of medications) of all first line medical therapies as recommended by the medical compendia and standard of care guidelines or has a documented medical reason (i.e. intolerance, contraindications, etc.) for not receiving or trying all first line medical treatment(s). · Documentation consistent with pharmacy claims data was submitted indicating the patient is not currently using any antineoplastic, immunosuppressant, or immunomodulating medications and does not have a history of progressive multifocal leukoencephalopathy (PML) and does not have a compromised immune system. · Documentation on request form indicates that the medication is recommended or prescribed by a physician who is authorized by the TOUCHTM program to prescribe TYSABRI® and that the patient is enrolled in the TOUCHTM program and has agreed to comply with the requirements for receiving TYSABRI®. · The medication is prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, DrugPoints, AHFS drug information) as defined by the Social Security Act. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR RE-AUTHORIZATION FOR USE IN OTHER MEDICALLY ACCEPTED INDICATIONS: · The medication is recommended or prescribed by a specialist for the respective treated disease state. · Diagnostic or clinical documentation was submitted (e.g. improved disease activity index, quality of life, blood work, radiographic evidence etc.) that indicates the member has significantly clinically benefited from receiving TYSABRI® therapy.

· · ·

Documentation on request form indicates that the medication is recommended or prescribed by a physician who is authorized by the TOUCHTM program to prescribe TYSABRI® and that the patient is enrolled in the TOUCHTM program and has agreed to comply with the requirements for receiving TYSABRI®. Documentation consistent with pharmacy claims data was submitted indicating the patient is not currently using any antineoplastic, immunosuppressant, or immunomodulating medications and does not have a history of progressive multifocal leukoencephalopathy (PML) and does not have a compromised immune system. Documentation that, and is being prescribed at a medically accepted dose per the medical compendia (i.e. micromedex, DrugPoints, AHFS) as defined by the Social Security Act.

If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. FDA INDICATIONS: Multiple Sclerosis: Tysabri® is indicated as monotherapy for the treatment of relapsing forms of multiple sclerosis in order to delay the accumulation of physical disability and to reduce frequency of clinical exacerbations. Tysabri® is generally recommended for patients who have an inadequate response to, or are unable to tolerate, alternate multiple sclerosis therapies. Crohn's Disease: Tysabri® is indicated for inducing and maintaining clinical response and remission in adult patients with moderately to severely active Crohn's disease with evidence of inflammation who have had an inadequate response to, or are unable to tolerate conventional Crohn's disease therapies and inhibitors to TNF-. DOSAGE AND ADMINISTRATION: 300 mg IV infused over approximately 1 hour, given at 4-week (28-day) intervals. Do not give as an intravenous push or bolus. · For the treatment of Crohn's Disease: Tysabri® should not be used with concomitant immunosuppressants (e.g. 6mercaptopurine, azathioprine, cyclosporine, or methtrexate) or concomitant inhibitors of TNF-. Aminosaliylates may be continued during treatment with Tysabri®. If the patient has not experience therapeutic benefits by 12 weeks of induction therapy then treatment discontinued. For patients that start Tysabri® while on chronic oral corticosteroids, commence steroid tapering as soon as therapeutic benefit has occurred. If the patient can not be tapered off of the oral corticosteroids within six months then Tysabri® should be discontinued. BOX 1: TREATMENT FAILURE:

A member may be considered to have failed treatment if any of the following are documented: 1. 2. 3. Member who has an attack rate (relapse) of more than 1 per year, fails to show a reduction in relapse rate, or continues to experience attacks (relapses) at a rate similar to that found before starting therapy** Member who has incomplete recovery (cumulative residual abnormalities sustained for 6 months) from repeated attacks, particularly as the EDSS score increases. ** Member experiences an annual increase in the EDSS (Expanded Disability Status Scale) of 1 point from a previous score of 3 to 5.5, or 0.5 point increase from a previous score of 6.0 or greater in the absence of clinical attacks or other documentation of clinically significant disability progression. ** Member who develops new or recurrent brainstem or spinal cord lesions as seen on MRI. ** Members experiencing relapses affecting multiple neurologic symptoms, and those accumulating residual impairments in multiple neurologic systems. ** Members who have progressive motor, cognitive or sensory impairment sufficient to disrupt their daily activities irrespective of changes on neurologic examination, provided the influence of depression, medications or superimposed concurrent disease is ruled out. Examples include: loss of endurance in sustaining activity, forced alterations in activities of daily living, muddled thinking, impaired concentration and mental processing and fatigue. ** Members who have new or enlarging T2 lesions, brain atrophy on MRI, or new T1 Gd enhancing lesions on MRI accompanied by changes in the ability to perform daily activities. **

4. 5. 6.

7.

** These are members who have a documented treatment failure after receiving a minimum of 6 months each of Copaxone® and Rebif®. Diagnostic or clinical documentation of treatment failure will be required for the last therapy the member received. This requires that he member has failed a minimum of 6 months of both therapies (Rebif® and Copaxone®) or has a documented medical reason (i.e. intolerance) for not utilizing both for a minimum of 6 months.

GLOSSARY:

TOUCHTM: is a distribution program designed to assess the risk of progressive multifocal leukoencephalopathy (PML) associated with TYSABRI®, minimize the risk of PML, minimize the death and disability due to PML, and promote informed risk-benefit decisions regarding TYSABRI® use. Kurtzke Expanded Disability Scale (EDSS) score: is a scale for evaluating the degree of neurologic impairment in MS. The EDSS score is measured in one-half point increments, from 0.0 (normal) to 10.0 (death). In order to rate a person on the EDSS, the neurologist first performs a standard neurologic examination to test strength, coordination, vision, walking, etc. The neurologist next summarizes the results of the neurological examination in several "Functional System Scores" as follows: pyramidal (strength and spasticity), cerebellar, brain stem, sensory, bowel and bladder, visual, cerebral and "other" functions. Finally, the neurologist uses the Functional System Scores along with ability to walk to rate the individual on the EDSS. The EDSS score is most reflective of lower limb function. Since this scoring system does not account for other signs and symptoms of MS, it is not used as an absolute measure of disability. But the EDSS can be a good gauge of disease progression. Other scales are used to measure fatigue, symptoms affecting the upper body, and mental changes. Kurtzke Expanded Disability Status Scale (EDSS) Rating Status Normal Neurological Exam No Disability, minimal symptoms No disability, minimal signs in more than one area Slightly more disability in one area Slightly greater disability in two areas Moderate disability in one area but still walking independently Walking independently but with moderate disability in one area and more than minimal disability in several others 4.0 Walking without aid, self-sufficient, up and about some12 hours a day despite relatively severe disability; able to walk without aid or rest some 500 meters 4.5 Walking without aid, up and about much of the day, able to work a full day, may have some limitation of full activity or require some help, relatively severe disability but able to walk without aid or rest some 300 meters. 5.0 Walking without aid or rest for about 200 meters, disability severe enough to impair full daily activities, can work a full day without special provisions 5.5 Ambulatory without aid or rest for about 100 meters; disability severe enough to prevent full daily activities 6.0 Intermittent or unilateral constant assistance (cane, crutch, brace) required to walk about 100 meters with or without resting 6.5 Needs canes, crutches, braces to walk for 20 meters without resting 7.0 Unable to walk beyond five meters even with aid; mostly confined to a wheelchair; wheels self in standard wheelchair and transfers alone; up and about in wheelchair some 12 hours a day 7.5 Unable to take more than a few steps; restricted to wheelchair; may need aid in transfer; wheels self but cannot carry on in standard wheelchair a full day; may require motorized wheelchair 8.0 Essentially restricted to bed, chair, or wheelchair, but may be out of bed itself much of the day; retains many self-care functions; generally has effective use of arms 8.5 Essentially restricted to bed much of day; has some effective use of arms; retains some self-care functions 9.0 Helpless bed patient; can communicate and eat 9.5 Totally helpless bed patient; unable to communicate effectively or eat/swallow 10.0 Death due to MS

Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology.1983;33:1444-1452.

0 1.0 1.5 2.0 2.5 3.0 3.5

Relapse: is the occurrence, recurrence, or worsening of symptoms of neurological dysfunction lasting more than 24 hours and then stabilizing or eventually resolving either partially or completely. REFERENCES:

1. Cohen BA. Khan O. Jeffery DR. et al. Identifying and treating patients with suboptimal responses. Neurology.2004;63(Suppl 6):S33-S40.

2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21.

22. 23. 24. 25. 26. 27. 28. 29.

Lee MA. Smith L. Palace J. et al. Spatial mapping of T2 and gadolinium-enhancing T1 lesion volumes in multiple sclerosis: evidence for distinct mechanisms of lesion genesis.? Brain.199;122:1261-1270. Rovaris M. Comi G. Filippi M. MRI markers of destructive pathology in multiple sclerosis-related cognitive dysfunction. Journal of the Neurological Sciences.2006;245:111-116. Brex P. Ciccarelli O. O'Riordan J. et al. A longitudinal study of abnormalities on MRI and disability from MS. The New England Journal of Medicine.2002;246 (3):158-164. Miller DH. Grossman RI. Reingold SC. Et al The role of magnetic resonance techniques in understanding and managing MS. Brain.1998;121:3-24. Lycklama GJ. Van Walderveen MAA. Castelijns JA. Et al. Brain and spinal cord abnormalities in multiple sclerosis. Correlation between MRI parameters, clinical subtypes and symptoms. Brain.1998; 121:687-697. O'Riordan JI. Thompson AJ. Kingsley DPE.et al. The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10year follow-up. Brain.1998;121:495-503. Rooney WD. Coyle PK. Recent advances in the neuroimaging of MS.Current Neurology and Neuroscience Reports.2005;5:217-224. Polman CH, O'Connor PW, Havrdova E, et al: A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354(9): 899-910. Dalton CM. Miszkiel KA. Barker DG. Et al. Effect of natalizumab on conversion of gadolinium enhancing lesions to T1 hypointense lesions in relapsing multiple sclerosis. Journal of Neurology.2004;251:407-413. Tysabri package insert. Cambridge, MA: Biogen Idec; 2008 October. [Homepage on the internet] www.micromedex.com. Tysabri. Thompson Healthcare. Copyright ©1974-2006. Accessed through www.usip.edu on 07/20/2006 Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology.1983;33:14441452. http://www.multiplesclerosis.com Rovaris M. Comi G. Filippi M. MRI markers of destructive pathology in multiple sclerosis-related cognitive dysfunction. Journal of the Neurological Sciences.2006;245:111-116. Polman CH. Reingold SC. Edan G. et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria".Annals of Neurology.2005;58:840-846. Rudick, RA. Lee JC. Simon J. Fisher E. Significance of T2 lesions in multiple sclerosis: A 13-year longitudinal study. Annals of Neurology.2006;60:236-242. Rieckmann P. Toyka KV. Escalating immunotherapy of multiple sclerosis. New aspects and practical application. Multiple Sclerosis Therapy Consensus Group (MSTCG). Journal of Neurology. 2004;251:1329-1339. Leary SM. Porter B. Thompson AJ. Multiple sclerosis: diagnosis and the management of acute relapses. Postgraduate Medicine Journal. 2005;81:302-308. National Multiple Sclerosis Society. Expert Opinion Paper. Medical advisory board of the National MS Society. Treatment recommendations for physicians. Disease management consensus statement.2005. Available at www.nationalmssociety.org/PRC.asp National Multiple Sclerosis Society. Expert Opinion Paper. Medical advisory board of the National MS Society. Treatment recommendations for physicians. Changing therapy in relapsing multiple sclerosis: Considerations and recommendations of a task force of the National MS Society.2004. Available at www.nationalmssociety.org/PRC.asp Rio J. Nos C. Tintore M. et al. Assessment of different treatment failure criteria in a cohort of RRMS patients treated with interferon : implications for clinical trials. Annals of Neurology. 2002;52:400-406. Rio J. Nos C. Tintore M. et al. Defining the response to interferon- in RRMS patients. Annals of Neurology.2006;59:344-352. Goodin DS. Arnason BG. Coyle PK. Et al. The use of mitoxantrone (Novantrone) for the treatment of MS. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology.2003;61:1332-1338. Multiple Sclerosis International Federation. Available at: www.msif.org. All about MS. Available at www.mult-sclerosis.org. Sandborn WJ, Colombel JF, Enns R, et al. Natalizumab Induction and Maintenance Therapy for Crohn's Disease. The New England Journal of Medicine 2005; 353: 1912-25. Targan SR, Feagan BG, Fedorak RN, et al. Natalizumab for the Treatment of Active Crohn's Disease: Results of the ENCORE Trial. Gastroenterology 2007; 132: 1672-83. Feagan BG, Sandborn WJ, Hass S, et al. Health-Related Quality of Life During Natalizumab Maintenance Therapy for Crohn's Diease. American Journal of Gastroenterology 2007; 102:2737-46.

Revision/Review Date: 8/2011 Associated Policy: Prior Authorization of Medications 236.200

NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION PROTOCOL FOR WHITE BLOOD CELL STIMULATORS Neupogen® (filgrastim) 300 mcg/mL preservative-free (PF) vial, 300 mcg/0.5 mL prefilled syringe PF; 480 mcg/1.6 mL PF vial, 480 mcg/0.8 mL prefilled syringe PF. Leukine® (sargramostim) 250 mcg lyophilized powder for injection PF vial, 500 mcg/mL solution multi-dose vial * Neulasta® (pegfilgrastim) 6 mg/0.6mL prefilled syringe for subcutaneous injection Initial Approval The request for the medication is for an Food and Drug Administration (FDA) approved indication, and/or is used for a medical condition (see medically accepted uses section below) that is supported by the medical compendium (Micromedex, American Hospital Formulary Service (AHFS), Drug Points, and the Drug Package Insert) as defined in the Social Security Act 1927 and/or per the National Comprehensive Cancer Network (NCCN) or the American Society of Clinical Oncology (ASCO) standard of care guidelines. Documentation is submitted of the patient's current diagnosis, current body weight, body surface area (needed for Leukine request only) and absolute neutrophil count (within 30 days of the request). Prescribed dosing of medication is within FDA approved indications and/or is supported by the medical compendium as defined by the Social Security Act and/or per the NCCN or ASCO standard of care guidelines. If all of the above conditions are met, the request will be approved for up to 12 weeks or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per the NCCN or ASCO standard of care guidelines; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Reauthorization of Medication The prescribing physician has provided documentation as to the clinical benefits of the medication supporting continued treatment, OR the medication is being continued in accordance with the recommended time as defined by FDA drug package insert, and/or per recommendations of the medical compendium as described above, and/or per the NCCN or ASCO standard of care guidelines. Documentation is submitted of the patient's absolute neutrophil count (within 30 days of the request). Prescribed dosing of medication is within FDA approved indications and/or supported by the medical compendium as defined by the Social Security Act and/or per the NCCN or ASCO standard of care guidelines. If all of the above conditions are met, the request will be approved for up to 12 weeks or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per the NCCN or ASCO standard of care guidelines; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Medically Accepted Dosing ASCO and NCCN practice guidelines prefer the subcutaneous route of administration for all 3 white blood cell stimulators. Per ASCO guidelines the calculated dose may be rounded off, within reason, to the nearest vial/syringe size to reduce wastage.

FDA APPROVED INDICATIONS AND DOSING:

Neupogen® (filgrastim) Adult dosing: Patients Receiving Myelosuppressive Chemotherapy: The recommended starting dose of Neupogen® is 5 mcg/kg/day, administered as a single daily injection SC bolus injection, by short IV infusion (15 to 30 minutes), or by continuous SC or continuous IV infusion. Doses may be increased in increments of 5 mcg/kg for each chemotherapy cycle, according to the duration and severity of the ANC nadir. Therapy with Neupogen should be discontinued if the ANC surpasses 10,000/mm3 after the expected chemotherapy-induced neutrophil nadir. Cancer Patients Receiving Bone Marrow Transplant (BMT): The recommended dose of Neupogen following BMT is 10 mcg/kg/day given as an IV infusion of 4 to 24 hours, or as a continuous 24 hour SC infusion. The daily dose of Neupogen should be titrated against the neutrophil response as follows: Absolute Neutrophil Count When ANC > 1000/mm3 for 3 consecutive days Then: Neupogen Dose Adjustment Reduce to 5 mcg/kg/day Discontinue Neupogen

If ANC remains > 1000/mm3 for 3 consecutive days Then: If ANC decreases < 1000/mm3

Resume at 5 mcg/kg/day

If ANC decreases to < 1000/mm3 at any time during the 5 mcg/kg/day administration, Neupogen should be increased to 10 mcg/kg/day, and the above steps should then be followed. Patients with Congenital neutropenia: 6 mcg/kg SC twice daily based on ANC results and clinical course. Patients Undergoing Peripheral Blood Progenitor Cell Collection (PBPC) and Therapy: The recommended dose of Neupogen for the mobilization of PBPC is 10 mcg/kg/day SV, either as a bolus or a continuous infusion. It is recommended that Neupogen be given for at least 4 days before the first leukapharesis procedure and continued until the last leukapharesis. Neupogen dose modification should be considered for those patients who develop a WBC count > 100,000/mm3. Patients with Severe Chronic Neutropenia, Idiopathic or Cyclic: The recommended daily starting dose is 5 mcg/kg as a single injection SC every day. Pediatric dosing: ASCO has no official recommendation, but states that adult doses have been used in pediatric patients; NCCN has no information on pediatric patients). Based on the Compendia pediatric dosing was available for: Chemotherapy-induced Neutropenia, BMT to reduce the duration of neutropenia and neutropenia-related clinical sequelae in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy prior to BMT, Peripheral Blood Progenitor Cell Transplantation; and Congenital, Cyclic and Idiopathic neutropenia. Follow adult dosing guidelines for pediatric dosing for aforementioned indications. Leukine® (sargramostim) Adult dosing: Use Following Induction Chemotherapy in Acute Myelogenous Leukemia (AML): The recommended dose is 250 mcg/m2/day administered intravenously over a 4 hour period starting approximately on day 11 or four days following the completion of induction chemotherapy. Leukine treatment should be continued until an ANC <1500 cells/mm3 for 3 consecutive days or a maximum of 42 days. Use in Mobilization and Following Transplantation of Autologous Peripheral Blood Progenitor Cells: The recommended dose is 250 mcg/m2/day administered IV over 24 hours or SV once daily. Leukine treatment should be continued until an ANC <1500 cells/mm3 for 3 consecutive days. Use in Myeloid Reconstitution after Autologous or Allogenic Bone Marrow Transplantation: The recommended dose is 250 mcg/m2/day administered IV over a 2 hour period beginning two to four hours after bone marrow infusion and not less than 24 hours after the last dose of chemotherapy or radiotherapy. Leukine treatment should be continued until an ANC <1500 cells/mm3 for 3 consecutive days. Use in Bone Marrow Transplantation Failure of Engraftment Delay: The recommended dose is 250 mcg/m2/dayfor 14 days as a 2 hour IV infusion. The dose can be repeated after 7 days off therapy if engraftment has not occurred. Pediatric dosing: Safety and efficacy in pediatric patients has not been established; however, available safety data indicate that Leukine does not exhibit any greater toxicity in pediatric patients than in adults. Neulasta® (pegfilgrastim) Adult dosing: Chemotherapy-induced Febrile Neutropenia Prophylaxis: The recommended dose of Neulasta is a single SC injection of 6 mg administered once per chemotherapy cycle. Neulasta should not be administered in the period between 14 days before and 24 hours after administration of cytotoxic chemotherapy. Pediatric dosing:

Safety and efficacy have not been established; the 6 mg fixed-dose single-use syringe formulation should not be used in infants, children, and smaller adolescents weighing less than 45 kg. Revision/Review Date: 05/2009 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary. References: 1. Leukine® Prescribing Information. Berlex. April 2008.. 2. Neulasta® Prescribing Information. Amgen Inc. April 2008. 3. Neupogen® Prescribing Information. Amgen Inc. September 2007 4. ASCO Guidelines. 2000 Update of Recommendation for the use of Hematopoietic Colony-Stimulating Factors: EvidenceBased, Clinical Practice Guidelines. 5. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology Myeloid Growth Factors in Cancer Treatment. V 6. Stull DM, Bilmes R, Kim H, Fichtl R. Comparison of sargramostim and filgrastim in the treatment of chemotherapy-induced neutropenia. Am J Health Syst Pharm. 2005;62(1):83-87.

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA XELODATM (capecitabine): Tablets: 150 mg, 500 mg STATUS: Non-Preferred

PA CRITERIA FOR APPROVAL FOR BREAST CANCER: · Documentation that the patient has advanced or metastatic breast cancer. AND · When used in combination therapy: o With Taxotere® (Docetaxel), documentation that the patient has failed to respond to, or relapsed during or following, an anthracycline-containing chemotherapy regimen. OR o With Tykerb®, then refer to the Tykerb® protocol for the prior authorization criteria. · When use as monotherapy therapy o Documentation that the patient is resistant to both paclitaxel AND an anthracycline-containing chemotherapy regimen OR anthracycline therapy is not indicated in that patient. AND · The medication is being prescribed at a dose that is within FDA approved guidelines and/or is supported by the medical compendium as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or American Society of Clinical Oncology (ASCO) standard of care guidelines. If the above conditions are met, the request will be approved for a duration of 6 months; if the above conditions are not met, the request will be referred to a Pharmacist for medical necessity review. PA CRITERIA FOR APPROVAL FOR COLORECTAL CANCER: · Documentation that the patient has stage III (Duke's C) colon cancer OR stage IV colorectal cancer. AND · The medication is being prescribed at a dose that is within FDA approved guidelines and/or is supported by the medical compendium as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or American Society of Clinical Oncology (ASCO) standard of care guidelines. If the above conditions are met, the request will be approved for a duration of 6 months; if the above conditions are not met, the request will be referred to a Pharmacist for medical necessity review. PA CRITERIA FOR AUTHORIZATION FOR USE IN A NON-FDA APPROVED MEDICALLY ACCEPTED INDICATION: · · The medication is recommended and prescribed by a specialist in the field to treat the member's respective medical condition. The medication is prescribed for a non-FDA approved indication but is considered to be a medically accepted use of the medication per the medical compendia (i.e. Micromedex, DrugPoints [formerly known as USPDI] and AHFS drug information) as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or the American Society of Clinical Oncology (ASCO). Documentation was submitted indicating that the member has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates, doses of medications) of all first line medical therapies as recommended by the medical compendia and standard care

·

·

guidelines and/or has another documented medical reason (i.e. intolerance, contraindications, etc.) for not receiving or trying all first line medical treatment(s). The medication is prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, DrugPoints [formerly known as USPDI] and AHFS drug information) as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or the American Society of Clinical Oncology (ASCO).

If all of the above conditions are met, the request will be approved for up to a 6 month duration. If all of the above criteria are not met, the request is referred to a Pharmacist for medical necessity review. FDA INDICATIONS: Breast Cancer: · When used in combination with Taxotere® (docetaxel) for the treatment of patients with metastatic breast caner after failure of prior anthracycline-containing chemotherapy. · When used as monotherapy, indicated for patients with metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen or resistant to paclitaxel and for whom further anthracycline therapy is not indicated (i.e. patients who have received cumulative doses of 400 mg/m2 of doxorubicin or doxorubicin equivalents). Resistant is defined as progressive disease while on treatment, with or without an initial response, or relapse within 6 months of completing treatment with an anthracycline-containing adjuvant regimen. Colorectal Cancer: · Indicated as a single agent for adjuvant therapy for patients with Dukes' C colon cancer who have undergone complete resection of the primary tumor when treatment with fluoropyrimidine therapy alone is preferred. · Indicated as first-line treatment of patients with metastatic colorectal carcinoma when treatment with fluoropyrimidine therapy alone is preferred. NON-FDA MEDICALLY APPROVED INDICATION: Pancreatic cancer, gastric cancer, ovarian cancer and metastatic renal cell carcinoma. DOSAGE AND ADMINISTRATION: Breast Cancer · Combination Therapy: 1250 mg/m2 twice daily (2500 mg/m2 total daily dose) for two weeks followed by a 1-week rest period; courses of therapy are given in 3-week cycles. · Combination Therapy with Tykerb®: 2000 mg/m2/day (divided into 2 doses every 12 hours) for two weeks followed by a 1-week rest period; courses of therapy are given in 3week cycles. · Monotherapy: 1250 mg/m2 twice daily (2500 mg/m2 total daily dose) for two weeks followed by a 1-week rest period; courses of therapy are given in 3-week cycles. Colorectal Cancer · Adjuvant Therapy for Colorectal Cancer: 1250 mg/m2 twice daily (2500 mg/m2 total daily dose) for two weeks followed by a 1-week rest period; courses of therapy are given in 3-week cycles for a total of 8 cycles and a treatment period of 6 months. · First-line Therapy for Metastatic Colorectal Cancer: 1250 mg/m2 twice daily (2500 mg/m2 total daily dose) for two weeks followed by a 1-week rest period; courses of therapy are given in 3-week cycles. XELODA® dosage may need to be individualized to optimize patient management, as a result a lower dose may be acceptable provided a patient's inability to tolerate a full dose is documented.

Xeloda® Dose Calculations According to Body Surface Area Dose for 1250 mg/m2 Twice a Day Surface Area (m2) < 1.25 1.26 ­ 1.37 1.38 ­ 1.51 1.52 ­ 1.65 1.66 ­ 1.77 1.78 ­ 1.91 1.92 ­ 2.05 2.06 ­ 2.17 > 2.18 Total Daily Dose (mg) 3000 3300 3600 4000 4300 4600 5000 5300 5600 Number of Tablets to be Taken at Each dose (morning and evening) 150mg 500mg 0 1 2 0 1 2 0 1 2 3 3 3 4 4 4 5 5 5

DOSAGE MODIFICATIONS: Renal Impairment: · If patient creatinine clearance is 51- 80 ml/min: No adjustment needed. · If patient's creatinine clearance is 30 -50 ml/min: Administer 75% of normal dose. · If patient's creatinine clearance is <30 ml/min: The use of Xeloda is contraindicated. Hepatic impairment: · With mild-to-moderated impairment: no starting dose adjustment is necessary, however it is advised to monitor the patient carefully. · With severe hepatic impairment: these patients have not been studied. REFERENCES: 1. NCCN Clinical Practice Guidelines in OncologyTM: Breast Cancer; V.2.2007. 2. NCCN Clinical Practice Guidelines in OncologyTM: Colon Cancer, V.1.2008. 3. NCCN Clinical Practice Guidelines in OncologyTM: Rectal Cancer, V.1.2008. 4. Xeloda® Prescribing Information, Roche Pharmaceutical, 1999. 5. AHFS 2006-07. 6. Micromedex® 2007. Revision/Review Date: 8/2008 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Pharmacist review must override criteria when, in his/her professional judgment, the requested item is medically necessary.

SELECT HEALTH PRIOR AUTHORIZATION CRITERIA Xolair® (omalizumab): Formulary Status- Non Formulary PA CRITERIA FOR INITIAL APPROVAL: · The physician who has requested Xolair is pulmonologist or allergist or documentation (consultation) was submitted with the request indicating that Xolair was recommended by a pulmonologist or allergist. · The patient's age is > 12 years old and the patient has a > 1 year history of moderate-to-severe asthma · The patient's total serum IgE 30 IU/ml to 700 IU/ml and the prescribed dose is within approved FDA dosing guidelines. · The patient has a documented baseline FEV1 < 80% of predicted or FEV1/FVC that has been reduced by at least 5% of normal for the patient age range (see Table 1 below). · The patient has a documented history of one or more of the following: requires daily use of inhaled short acting B2 agonists, history of daily or continual asthma symptoms, limited physical activity or activity affected by exacerbations due to asthma, and frequent (> once per week) nighttime symptoms. · Documentation that the patient is still having significant symptoms (i.e. hospital admission, emergency room visits, or the severe of asthma exacerbations) while compliant on a high-dose inhaled corticosteroid with a long-acting B2 agonists + a leukotriene receptor antagonist or theophylline. If the patient utilizing these therapies then the patient must have a documented medical reason for not maximizing both high dose inhaled corticosteroids with long acting bronco dilator medication (e.g. side effects, intolerance, and hypersensitivity). · The patient has a positive documented immediate response on RAST test or skin prick test to at least 1 common allergen (e.g. dermatophagoides farinae, dermatophagoides pteronyssinus, dog, cat, or cockroach) and there is documented evidence that the positive skin tested allergen(s) is an asthma trigger either from environmental exposure or from testing or from attempted allergen immunotherapy. · Documentation was submitted that the patient has received immunotherapy and despite this the patient had documented clinical asthma recurrence/persistence precipitated by the allergen(s) for which the patient is receiving immunotherapy that had resulted in a hospital admission or emergency room visit. OR if the patient has not received allergy shots they have a documented medical reason for not taking allergy shots (e.g. severe, unstable asthma or severe, systemic injection reactions). · Documentation was submitted indicating what environmental measures were attempted to avoid or minimize exposure to identified allergen asthma triggers OR a reason (e.g. unavoidable allergen) for not trying to avoid asthma allergen trigger(s). · The patient is not receiving any medication (e.g. Beta Blockers or NSAIDs) that could cause bronchospasm or cause an asthma exacerbation and if the patient is on a potential asthma inducing medication, that there is a documented medical reason for continuing that medication as well as documentation that the medication is not a cause for worsening asthma or causing any asthma symptoms. If all of the above conditions are met, the request will be approved with a 4-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR REAUTHORIZATION AFTER 4 MONTHS OF THERAPY: · Documentation submitted indicates that the member has significantly clinically benefited from the medication (e.g. patient has marked improvement in pulmonary function tests such as FEV1 or peak expiratory flow rate, decrease in asthma exacerbations or a decrease in inhaled or oral corticosteroid use since receiving Xolair therapy). · The prescribed dose is within approved FDA dosing guidelines. If all of the above conditions are met, the request will be approved with a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. FDA INDICATION: Xolair is indicated for the treatment of adults and adolescents (> 12 years old) with moderate to severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids. DOSAGE AND ADMINITRATION: Pretreatment Serum IgE(IU/ml) 30-60

Body Weight (Kg)

>60-70

>70-90

>90-150

Pretreatment Serum IgE(IU/ml) 30-60 30-100 150mg q 4 weeks > 100-200 300mg q 4 weeks > 200-300 300mg q 4 weeks > 300-400 225mg 2 weeks > 400-500 300mg q 2 weeks > 500-600 300mg q 2 weeks > 600-700 375mg q 2 weeks

Body Weight (Kg)

>60-70

>70-90

>90-150

150mg q 4 weeks 300mg q 4 weeks 225 mg q2 weeks 225mg q 2 weeks 300mg q 2 weeks 375mg q 2 weeks DO NOT DOSE

150mg q 4 weeks 300mg q 4 weeks 225mg q 2 weeks 300mg q 2 weeks

300mg q 4 weeks 225mg q 2 weeks 300mg q 2 weeks DO NOT DOSE DO NOT DOSE

375mg q 2 weeks DO NOT DOSE DO NOT DOSE DO NOT DOSE DO NOT DOSE

Approved dosing is based on FDA dosing guidelines as summarized in the above chart. However, due to the long half life of the medication and the fact that the medication can be dosed once a month, total monthly doses will be approved in order to prevent wasting of medication due to split vial dosing (i.e. 375 mg every 2 weeks would be approved to be dosed as 450 mg then in 2 weeks 300 mg, i.e. 225 mg q2weeks would be approved 300 mg then in 2 weeks 150 mg ­ in both examples total administered drug is the same, and it benefits the member because they receive one less injection of medication). Table 1: Normal FEV1/FVC Patients Age: Normal Values: 8 ­ 19 y/o 85 % 20 ­ 39 y/o 80 % 40 ­ 59 y/o 75 % 60 ­ 80 y/o 70 % DOSAGE ADJUSTMENTS Total IgE levels are elevated during treatment and remain elevated for up to one year after the discontinuation of treatment. Therefore, re-testing of IgE levels during Xolair treatment cannot be used as a guide for dose determination. Dose determination after treatment interruptions lasting less than 1 year should be based on serum IgE levels obtained at the initial dose determination. Total serum IgE levels may be re-tested for dose determination if treatment with Xolair has been interrupted for one year or more. Doses should be adjusted for significant changes in body weight. GLOSSARY: FEV1 ­ forced expiratory volume in one second (measured using spirometry) FVC ­ forced vital capacity PEF ­ peak expiratory flow (measured using home peak flow meter) PEFR ­ peak expiratory flow rate REFERENCES:

1. 2. 3. 4. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. The National Heart Lung and Blood Institute. NIH publication. Updated August 2007. Available at http://www.nhlbi.nih.gov/guidelines/. Accessed May 2009. Corren J, Casale T, Deniz Y, Ashby M. Omalizumab, a recombinant humanized anti-IgE antibody, reduces asthma-related emergency room visits and hospitalizations in patients with allergic asthma. J Allergy Clin Immunol 2003; 111(1):87-90. Finn A, Gross G, van Bavel J, Lee T, et al. Omalizumab improves asthma-related quality of life in patients with severe allergic asthma. J Allergy Clin Immunol 2003; 111(2):278-284. Pulmonary-Allergy Drugs Advisory Committee. Biologics License Application. (BLA)

5. 6. 7. 8. 9.

http://www.fda.gov/ohrms/dockets/ac/cder03.html#PulmonaryAllergyDrugs Adkinson, NF et al. A controlled trial of immunotherapy for asthma in allergic children. N Engl J Med 1997; 336:324-331. Li, James et al. Allergen Immunotherapy: a practice parameter. Annals of Allergy, Asthma, and Immunology 2003; 90:1-40. Ross, RN et al. Effectiveness of a specific immunotherapy in the treatment of asthma: a meta analysis of prospective, randomized, double-blind, placebo controlled studies. Clin Ther 2000; 22:329-341. Cantani, A et al. A three year prospective study of specific immunotherapy to inhalent allergens: evidence of safety and efficacy in 300 children with allergic asthma. J Investig Allergol Clin Immunol 1997; 7:90-97. Xolair® Prescribing Information. Genentech, Inc. January 2010.

Revision/Review Date: 5/2010

Associated Policy: Prior Authorization of Medications 236.200

NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

Information

Specialty/Injectable Pharmacy Prior Authorization Criteria - Pharmacy - First Choice - Select Health of South Carolina

125 pages

Report File (DMCA)

Our content is added by our users. We aim to remove reported files within 1 working day. Please use this link to notify us:

Report this file as copyright or inappropriate

401110