Clinical Policy: Reference Number: CP.HNMC.05 Effective Date: 11.16.16 Last Review Date: 11.17 Line of Business: Medicaid Medi-Cal Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description The following are requiring prior authorization: Lovastatin Extended Release (Altoprev ), Rosuvastatin (Crestor ), Pitavastain (Livalo ), Ezetimibe/Simvastatin (Vytorin ). FDA approved indication Lovastatin Extended Release (Altoprev) is indicated as an adjunctive therapy to diet to: Reduce the risk of myocardial infarction (MI), revascularization procedures, and angina in patients without CHD, but with multiple risk factors. 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). 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 Rosuvastatin (Crestor) is indicated for: 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. Pediatric patients 8 to 17 years of age with heterozygous familial hypercholesterolemia (HeFH) to reduce elevated total-c, LDL-C and ApoB after failing an adequate trial of diet therapy. Pediatric patients 7 to 17 years of age with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C, total-c, nonhdl-c and ApoB as an adjunct to diet, either alone or with other lipid-lowering treatments. Hypertriglyceridemia: As adjunctive therapy to diet. Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia): As adjunctive therapy to diet. Homozygous Familial Hypercholesterolemia (HoFH): to reduce LDL-C, Total-C, and ApoB. Slow the Progression of Atherosclerosis: As part of a treatment strategy to lower total-c and LDL-C as an adjunct to diet. Risk reduction of MI, stroke, and arterial revascularization procedures in patients without clinically evident CHD, but with multiple risk factors. Page 1 of 8
Pitavastain (Livalo) is indicated for: 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. Ezetimibe/Simvastatin (Vytorin) is indicated for: 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. Limitation of use: Crestor has not been studied in Fredrickson Type I and V dyslipidemias Altoprev and Livalo has not been studied in Fredrickson Types I, III, and V dyslipidemias Vytorin: o No incremental benefit of VYTORIN on cardiovascular morbidity and mortality over and above that demonstrated for simvastatin has been established o Vytorin has not been studied in Fredrickson Type I, III, IV, and V dyslipidemias. Livalo o Doses of Livalo greater than 4 mg once daily were associated with an increased risk for severe myopathy in premarketing clinical studies. Do not exceed 4 mg once daily dosing of Livalo. o The effect of Livalo on cardiovascular morbidity and mortality has not been determined. Policy/Criteria Provider must submit documentation (which may include office chart notes and lab results) supporting that member has met all approval criteria It is the policy of health plans affiliated with Centene Corporation that Altoprev, Crestor, Livalo, and Vytorin are medically necessary when the following criteria are met: I. Initial Approval Criteria A. All Indications (must meet all): 1. For Altoprev and Livalo: Failure to achieve National Cholesterol Education Program (NCEP) goals OR failure of TWO generic formulary statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin) unless contraindicated or clinically significant adverse effects are experienced; 2. For Crestor and Vytorin: Failure to achieve NCEP goals OR failure of ONE generic formulary statin (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin) unless contraindicated or clinically significant adverse effects are experienced; 3. For Vytorin 10/80 mg requests, the patient has been taking 80 mg of simvastatin for 12 months or longer; 4. For Crestor 40 mg requests, failure to achieve NCEP goals on Crestor 20 mg; Page 2 of 8
5. Dose does not exceed: a. Altoprev 60 mg/day b. Livalo 4 mg/day c. Crestor 40 mg/day d. Vytorin 10 mg/day ezetimibe and 40 mg/day simvastatin for most patients; 80 mg/day simvastatin for patients already taking 80 mg/day chronically without evidence of myopathy. Approval duration: Length of Benefit B. Other diagnoses/indications 1. Refer to CP.PMN.53 if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) II. Continued Therapy A. All Indications (must meet all): 1. Currently receiving medication via a health plan affiliated with Centene Corporation or member has previously met initial approval criteria; 2. Member is responding positively to therapy; 3. If request is for a dose increase, new dose does not exceed: a. Altoprev 60 mg/day b. Livalo 4 mg/day c. Crestor 40 mg/day d. Vytorin 10 mg/day ezetimibe and 40 mg/day simvastatin for most patients; 80 mg/day simvastatin for patients already taking 80 mg/day chronically without evidence of myopathy. Approval duration: Length of Benefit B. Other diagnoses/indications (must meet 1 or 2): 1. Currently receiving medication via a health plan affiliated with Centene Corporation and documentation supports positive response to therapy. Approval duration: Duration of request or 12 months (whichever is less); or 2. Refer to CP.PMN.53 if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) III. Diagnoses/Indications for which coverage is NOT authorized: A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off-label use policy CP.PMN.53 or evidence of coverage documents; B. Crestor total daily dose exceeding 40 mg; C. Titration to or a new start of an 80 mg daily equivalent of simvastatin. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key NCEP: National Cholesterol Education Program MI: myocardial infarction CHD: coronary heart disease Total C: total cholesterol LDL: low density lipoprotein Page 3 of 8
HDL: high density lipoprotein Apo B: apolipoprotein B TG: triglycerides nonhdl-c: non-high-density lipoprotein cholesterol HoFH: homozygous familial hypercholesterolemia HeFH: heterozygous familial hypercholesterolemia CVD: cardiovascular disease AUC: area under the curve OATP: organic anion transporting polypeptide Appendix B: General Information Relative LDL-lowering Efficacy of Statin and Statin-based Therapies: http://www.fda.gov/drugs/drugsafety/ucm256581.htm 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. 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. 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 Page 4 of 8
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. Appendix C: Therapeutic Alternatives Drug Dosing Regimen Dose Limit/ Maximum Dose atorvastatin (Lipitor) 10-80 mg PO QD 80 mg/day Age 10 to 17 years: 20 mg/day simvastatin (Zocor) 5-80 mg PO QD 80 mg/day lovastatin (Mevacor) pravastatin (Pravachol) Age 10 to 17 years: 40 mg/day 10-80 mg PO QD 80 mg/day 40 80 mg PO QD 10 40 mg PO QD Age 10 to 17 years: 40 mg/day 80 mg/day Age 8 to 13 years: 20mg/day Age 14 to 18 years: 40 mg/day Therapeutic alternatives are listed as Brand name (generic) when the drug is available by brand name only and generic (Brand name ) when the drug is available by both brand and generic. V. Dosage and Administration Drug Name Dosing Regimen Maximum Dose Lovastatin Extended 20-60 mg PO QD 60 mg per day Release (Altopre) Rosuvastatin (Crestor) 5-40 mg PO QD 40 mg per day In pediatric patients 10 to 17 years the usual dose range is 5-20 mg PO QD; doses greater than 20 mg have not been studied in this population Pitavastain (Livalo) 1-4 mg PO QD 4 mg per day Page 5 of 8
Ezetimibe/Simvastatin (Vytorin) 10/10-10/40 mg PO QD Use of the 10/80 mg dose of Vytorin should be restricted to patients who have been taking Vytorin 10/80 mg for 12 months or more without evidence of muscle toxicity 10/40 mg per day for most patients; 80 mg/day simvastatin for patients already taking 80 mg/day chronically without evidence of myopathy. VI. Product Availability Drug Lovastatin Extended Release (Altoprev ) Rosuvastatin (Crestor ) Pitavastain (Livalo ) Ezetimibe/Simvastatin (Vytorin ) Availability extended release tablets: 20 mg, 40 mg, 60 mg tablets: 5 mg, 10 mg, 20 mg, 40 mg tablets: 10/10 mg, 10/20 mg, 10/40 mg, 10/80 mg tablets: 1 mg, 2 mg, 4 mg VII. References 1. Altoprev [Prescribing Information]. Atlanta, GA: Shionogi Pharma; April 2014. 2. Crestor [Prescribing Information]. Wilmington, DE: AstraZeneca; May 2016. 3. Vytorin [Prescribing Information]. North Wales, PA: Merck Sharp & Dohme; March 2015. 4. Livalo. [Prescribing information] Kowa Pharmaceuticals. November 2016. 5. Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. 6. Executive Summary of the Third Report of the National Cholesterol Education Program 7. (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in 8. Adults (Adult Treatment Panel III). JAMA. May 16, 2001;285(19):2486-2497. 9. Micromedex Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed: January 12, 2016. 10. Clinical Pharmacology Web site. Available at: http://clinicalpharmacologyip.com/default.aspx. Accessed January 12, 2016. 11. Crestor. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed June 12, 2017. 12. Vytorin. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed June 12, 2017. 13. Livalo. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed June 12, 2017. 14. Altoprev. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed June 12, 2017. Reviews, Revisions, and Approvals Date P&T Approval Date Converted to new template; minor changes to verbiage and grammar. References updated. 06.13.17 11.17 Important Reminder Page 6 of 8
This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. Health Plan means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan s affiliates, as applicable. The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures. This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time. This clinical policy does not constitute medical advice, medical treatment or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members. This clinical policy is not intended to recommend treatment for members. Members should consult with their treating physician in connection with diagnosis and treatment decisions. Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan. This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, members and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, members and their representatives agree to be bound by such terms and conditions by providing services to members and/or submitting claims for payment for such services. Page 7 of 8
Note: For Medicaid members, when state Medicaid coverage provisions conflict with the coverage provisions in this clinical policy, state Medicaid coverage provisions take precedence. Please refer to the state Medicaid manual for any coverage provisions pertaining to this clinical policy. 2016 Centene Corporation. All rights reserved. All materials are exclusively owned by Centene Corporation and are protected by United States copyright law and international copyright law. No part of this publication may be reproduced, copied, modified, distributed, displayed, stored in a retrieval system, transmitted in any form or by any means, or otherwise published without the prior written permission of Centene Corporation. You may not alter or remove any trademark, copyright or other notice contained herein. Centene and Centene Corporation are registered trademarks exclusively owned by Centene Corporation. Page 8 of 8