Prior Authorization Protocol ALTOPREV (lovastatin extended release), CRESTOR (rosuvastatin), LIVALO (pitavastatin), VYTORIN (ezetimibe/simvastatin)

Transcription

1 ALTOPREV (lovastatin extended release), CRESTOR (rosuvastatin), LIVALO (pitavastatin), VYTORIN (ezetimibe/simvastatin) Coverage of drugs is first determined by the member`s pharmacy or medical benefit. Please consult with or refer to the Evidence of Coverage document. I. FDA Approved Indications: Altoprev: As an adjunctive therapy to diet to: Reduce the risk of myocardial infarction (MI), unstable angina, and/or coronary revascularization procedures in patients without symptomatic coronary heart disease (CHD), but at high risk. Slow the progression of coronary atherosclerosis in patients with CHD as part of a treatment strategy to lower total cholesterol (Total-C) and low-density lipoprotein cholesterol (LDL-C) to target levels. Reduce elevated Total-C, LDL-C, apolipoprotein B (Apo B), and triglyceride (TG) and to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary hypercholesterolemia (heterozygous familial and non-familial) and mixed dyslipidemia (Fredrickson types IIa and IIb,) Crestor: Primary Hyperlipidemia and Mixed Dyslipidemia: As adjunctive therapy to diet to reduce elevated Total-C, LDL-C, ApoB, non-high-density lipoprotein cholesterol (nonhdl-c), and TG and to increase HDL-C in adult patients with primary hyperlipidemia or mixed dyslipidemia. Heterozygous Familial Hypercholesterolemia (HeFH): As adjunctive therapy to diet to reduce Total-C, LDL-C and ApoB in children and adolescents8-17 years of age with HeFH if after an adequate trial of diet therapy the following findings are present: LDL-C >190 mg/dl or > 160 mg/dl and there is a positive family history of premature cardiovascular disease (CVD) or two or more other CVD risk factors. Hypertriglyceridemia: As adjunctive therapy to diet for the treatment of adult patients with hypertriglyceridemia. Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia): As adjunctive therapy to diet for the treatment of patients with primary dysbetalipoproteinema (Type III Hyperlipoproteinemia). Homozygous Familial Hypercholesterolemia: As adjunctive therapy to other lipid-lowering treatments (e.g., LDL apheresis) or alone if such treatments are unavailable to reduce LDL-C, Total-C, and ApoB in adult patients with homozygous familial hypercholesterolemia. Slow the Progression of Atherosclerosis: As adjunctive therapy to diet to slow the progression of atherosclerosis in adult patients as part of a treatment strategy to lower Total-C and LDL-C to target levels R. Gedey, P, S Spears, D. Duane, P, L Borichevskiy, P Page - 1

2 ALTOPREV (lovastatin extended release), CRESTOR (rosuvastatin), LIVALO (pitavastatin), VYTORIN (ezetimibe/simvastatin) Primary Prevention of Cardiovascular Disease: Reduce the risk of stroke, MI, and arterial revascularization procedures in individuals without clinically evident CHD but with an increased risk of cardiovascular disease based on: Age 50 years old in men and 60 years old in women High-sensitivity C-reactive protein (hscrp) 2 mg/l The presence of at least one additional cardiovascular disease risk factor such as hypertension, low HDL-C, smoking, or a family history of premature CHD. Vytorin: Primary Hyperlipidemia: Reduction of elevated Total-C, LDL-C, Apo B, TG and nonhdl- C, and to increase HDL-C in patients with primary (heterozygous familial and nonfamilial) hyperlipidemia or mixed hyperlipidemia. Homozygous Familial Hypercholesterolemia (HoFH): Reduction of elevated Total-C and LDL-C in patients with HoFH, as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable. Livalo: Primary Hyperlipidemia and Mixed Dyslipidemia: As an adjunctive therapy to diet to reduce elevated TC, LDL-C, Apo B, TG, and to increase HDL-C in adult patients with primary hyperlipidemia or mixed dyslipidemia. II. Health Net Approved Indications and Usage Guidelines: Altoprev, Livalo Failure to achieve National Cholesterol Education Program (NCEP) goals or clinically significant adverse effects to two generic formulary statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin) Crestor, Vytorin Failure to achieve NCEP goals or clinically significant adverse effects to one generic formulary statin (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin) AND For Vytorin 10/80 mg requests, the patient has been taking 80 mg of simvastatin for 12 months or longer AND For Crestor 40 mg requests, failure to achieve NCEP goals on Crestor 20 mg III. Coverage is Not Authorized For: R. Gedey, P, S Spears, D. Duane, P, L Borichevskiy, P Page - 2

3 ALTOPREV (lovastatin extended release), CRESTOR (rosuvastatin), LIVALO (pitavastatin), VYTORIN (ezetimibe/simvastatin) Crestor total daily dose exceeding 40 mg Titration to or a new start of an 80 mg daily equivalent of simvastatin Altoprev with concomitant administration of: Strong cytochrome P450 isoform 3A inhibitors (e.g., ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV Protease inhibitors, boceprevir, telaprevir, nefazodone) Erythromycin Vytorin with concomitant administration of: Strong cytochrome P450 isoform 3A4 (CYP3A4) inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, and cobicistatcontaining products) Gemfibrozil, cyclosporine, or danazol. Livalo with co-administration with cyclosporine. Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature. IV. General Information: Relative LDL-lowering Efficacy of Statin and Statin-based Therapies: Crestor has been shown to reduce LDL cholesterol by 45 to 63% with doses ranging from 5 mg to 40 mg/day. In a 6-week study, Crestor 40 mg reduced LDL cholesterol by 62.6% vs. Crestor 20 mg resulted in a LDL cholesterol reduction by 57%. Crestor given at 40 mg per day causes proteinuria as high as 10 times that of other statins. Proteinuria appears to be unique to Crestor and is not a statin class effect. Simvastatin is metabolized by the cytochrome P450 isoform 3A4. Certain drugs that inhibit this metabolic pathway can raise the plasma levels of the simvastatin component of Vytorin and may increase the risk of myopathy. Gemfibrozil can cause myopathy when used alone, and the risk of myopathy and rhabdomyolysis is increased by concomitant use with simvastatin. The area under the curve (AUC) and peak concentration (Cmax) of simvastatin are increased with concomitant gemfibrozil use. Due to the increased risk of myopathy, including rhabdomyolysis, associated with the 10/80 mg dose of Vytorin, patients unable to achieve their LDL-C goal utilizing the 10/40-mg dose of Vytorin should not be titrated to the 10/80-mg dose, but should be placed on alternative LDL-C-Iowering treatment(s) that provides greater LDL-C lowering. Crestor 80 mg can cause rhabdomyolysis in rare cases. There is no significant difference in reported incidences of myopathy or rhabdomyolysis between Crestor 40 mg and the highest commercially available doses of statins in clinical trials R. Gedey, P, S Spears, D. Duane, P, L Borichevskiy, P Page - 3

4 ALTOPREV (lovastatin extended release), CRESTOR (rosuvastatin), LIVALO (pitavastatin), VYTORIN (ezetimibe/simvastatin) Liver function tests are recommended before and at 12 weeks following both the initiation of therapy and any elevation of dose, and periodically (e.g. semiannually) thereafter. Crestor is contraindicated in patients with active liver disease or with unexplained persistent elevations of serum transaminases Pravastatin is FDA approved for pediatric patients 8 to 13 years up to 20 mg per day and 14 to 18 years up to 40 mg per day; simvastatin is FDA approved for pediatric patients 10 to 17 years of age up to 40 mg per day; lovastatin is FDA approved for pediatric patients 10 to 17 years of age up to 40 mg per day;and atorvastatin is FDA approved for pediatric patients 10 to 17 years of age up to 20 mg per day. Doses of Livalo greater than 4 mg once daily were associated with an increased risk for severe myopathy in pre-marketing clinical studies. Do not exceed 4 mg once daily dosing of Livalo. Cyclosporine is a known inhibitor of organic anion transporting polypeptide (OATP). Livalo is taken up into human hepatocytes mainly by OATP1B1. Cyclosporine may theoretically inhibit the uptake of Livalo into hepatocytes resulting in increased serum concentrations of Livalo with a 4.5 and 6.6 fold increase in Livalo AUC and Cmax, respectively. The risk of myopathy and rhabdomyolysis is increased by high levels of statin activity in plasma. Simvastatin and lovastatin is metabolized by the cytochrome P450 isoform 3A4. Certain drugs that inhibit this metabolic pathway can raise the plasma levels of simvastatin and may increase the risk of myopathy. V. Therapeutic Alternatives: Drug Dosing Regimen Dose Limit/Maximum Dose atorvastatin (Lipitor ) mg PO QD 80 mg/day (20 mg/day for pediatrics 10 to 17 years) simvastatin (Zocor ) 5-80 mg PO QD 80 mg/day (40 mg/day for pediatrics 10 to 17 lovastatin (Mevacor ) pravastatin (Pravachol ) *Requires Prior Authorization mg PO QD mg PO QD Pediatrics: mg PO QD years) 80 mg/day (40 mg/day for pediatrics 10 to 17 years) 80 mg/day Pediatrics: Age 8 to 13 years: 20 mg/day Age 14 to 18 years: 40 mg/day VI. Recommended Dosing Regimen and Authorization Limit: R. Gedey, P, S Spears, D. Duane, P, L Borichevskiy, P Page - 4

5 ALTOPREV (lovastatin extended release), CRESTOR (rosuvastatin), LIVALO (pitavastatin), VYTORIN (ezetimibe/simvastatin) Drug Dosing Regimen Authorization Limit Altoprev mg PO QD Length of benefit 5-40 mg PO QD Crestor In pediatric patients 10 to 17 years the usual dose range is 5-20 mg PO QD; Length of benefit doses greater than 20 mg have not been studied in this population Livalo 1-4 mg PO QD Length of Benefit 10/10-10/40 mg PO QD Use of the 10/80 mg dose of Vytorin Vytorin should be restricted to patients who have been taking Vytorin 10/80 mg for 12 Length of benefit months or more without evidence of muscle toxicity VII. VIII. Product Availability: Altoprev: 20 mg, 40 mg, 60 mg extended release tablet Crestor: 5 mg, 10 mg, 20 mg, 40 mg tablet Vytorin: 10/10 mg, 10/20 mg, 10/40 mg, 10/80 mg tablet Livalo: 1 mg, 2 mg, 4 mg tablet References: 1. Altoprev [Prescribing Information]. Atlanta, GA: Shionogi Pharma; April Crestor [Prescribing Information]. Wilmington, DE: AstraZeneca; November Vytorin [Prescribing Information]. North Wales, PA: Merck Sharp & Dohme; March Livalo. [Prescribing information] Kowa Pharmaceuticals. October Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. May 16, 2001;285(19): Micromedex Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed: January 12, Clinical Pharmacology Web site. Available at: Accessed January 12, Crestor. American Hospital Formulary Service Drug Information. Available at: 9. Vytorin. American Hospital Formulary Service Drug Information. Available at: 10. Livalo. American Hospital Formulary Service Drug Information. Available at: R. Gedey, P, S Spears, D. Duane, P, L Borichevskiy, P Page - 5

6 ALTOPREV (lovastatin extended release), CRESTOR (rosuvastatin), LIVALO (pitavastatin), VYTORIN (ezetimibe/simvastatin) 11. Altoprev. American Hospital Formulary Service Drug Information. Available at: The material provided to you are guidelines used by this plan to authorize, modify or determine coverage for persons with similar illnesses or conditions. Specific care and treatment may vary depending on individual need and the benefits covered under your contract R. Gedey, P, S Spears, D. Duane, P, L Borichevskiy, P Page - 6