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Lipotropics, Statins Therapeutic Class Review (TCR) October 2, 2020 No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, digital scanning, or via any information storage or retrieval system without the express written consent of Magellan Rx Management. All requests for permission should be mailed to: Magellan Rx Management Attention: Legal Department 6950 Columbia Gateway Drive Columbia, Maryland 21046 The materials contained herein represent the opinions of the collective authors and editors and should not be construed to be the official representation of any professional organization or group, any state Pharmacy and Therapeutics committee, any state Medicaid Agency, or any other clinical committee. This material is not intended to be relied upon as medical advice for specific medical cases and nothing contained herein should be relied upon by any patient, medical professional or layperson seeking information about a specific course of treatment for a specific medical condition. All readers of this material are responsible for independently obtaining medical advice and guidance from their own physician and/or other medical professional in regard to the best course of treatment for their specific medical condition. This publication, inclusive of all forms contained herein, is intended to be educational in nature and is intended to be used for informational purposes only. Send comments and suggestions to [email protected]. October 2020 Proprietary Information. Restricted Access – Do not disseminate or copy without approval. © 2004-2020 Magellan Rx Management. All Rights Reserved. AGENTS Drug Manufacturer amlodipine / atorvastatin generic, Pfizer (Caduet®)1 atorvastatin generic, Pfizer (Lipitor®)2 ezetimibe / simvastatin generic, Merck Sharp and Dohme (Vytorin®)3 fluvastatin4 generic fluvastatin ER generic, Novartis (Lescol XL®)5 lovastatin6 generic lovastatin ER Covis (Altoprev®)7 pitavastatin calcium Kowa (Livalo®)8 pitavastatin magnesium Medicure (Zypitamag®*)9 pravastatin generic; BMS (Pravachol®)10 rosuvastatin generic, AstraZeneca (Crestor®)11 rosuvastatin Sun (Ezallor™ Sprinkle*)12 simvastatin Salerno (Flolipid*)13 simvastatin generic, Merck Sharp and Dohme (Zocor®)14 * Simvastatin oral suspension (Flolipid), pitavastatin tablet (Zypitamag), and rosuvastatin (Ezallor) were approved as a New Drug Application (NDA) via the 505(b)(2) pathway. A 505(b)(2) NDA is a United States (US) Food and Drug Administration (FDA) approval pathway in which at least some of the information required for approval comes from studies not conducted by or for the applicant.15 Some of the data used for approval of Flolipid, Zypitamag, and Ezallor were derived from safety and efficacy data with simvastatin (Zocor), pitavastatin (Livalo), and rosuvastatin (Crestor), respectively. Lipotropics, Statins Review – October 2020 Page 2 | Proprietary Information. Restricted Access – Do not disseminate or copy without approval. © 2004-2020 Magellan Rx Management. All Rights Reserved. FDA-APPROVED INDICATIONS atorvastatin (Lipitor), fluvastatin, amlodipine/ ezetimibe/ simvastatin lovastatin ER Indications fluvastatin ER lovastatin21 atorvastatin* (Vytorin)18 (Altoprev)22 (Lescol XL)19,20 (Caduet)16,17 Primary hypercholesterolemia . Heterozygous familial and nonfamilial X X X X X Reduce: Total-C, LDL-C, TG and ApoB Increase: HDL-C Heterozygous familial X X X hypercholesterolemia 10–17 years -- -- 10–16 years 10–17 years . pediatric (Lipitor only) Mixed dyslipidemia Fredrickson Type X . IIa and IIb X X X To reduce X Reduce: Total-C, LDL-C, TG total-C, LDL-C and ApoB Increase HDL-C X X X -- X Hypertriglyceridemia X -- -- -- -- Fredrickson Type IV Primary dysbetalipoproteinemia X -- -- -- -- Fredrickson Type III Homozygous familial X X -- -- -- hypercholesterolemia Atherosclerosis -- -- X X X . slow progression Total-C = Total cholesterol; LDL-C = low density lipoprotein cholesterol; TG = triglycerides; ApoB = apoprotein B * Caduet is indicated when amlodipine and atorvastatin are both appropriate. Indications for amlodipine are hypertension, chronic stable angina, vasospastic angina, and angiographically documented coronary artery disease (CAD). Lipotropics, Statins Review – October 2020 Page 3 | Proprietary Information. Restricted Access – Do not disseminate or copy without approval. © 2004-2020 Magellan Rx Management. All Rights Reserved. FDA-Approved Indications (continued) atorvastatin (Lipitor), fluvastatin, amlodipine/ ezetimibe/ simvastatin lovastatin lovastatin ER Indications fluvastatin ER atorvastatin* (Vytorin) (Altoprev) (Lescol XL) (Caduet) CVD Reduces risk of MI, Reduces risk of MI, Reduces risk of MI, stroke, unstable angina, and need . primary prevention of -- -- unstable angina, coronary revascularization, angina for coronary coronary events revascularization revascularization CHD Reduces risk of MI, stroke . secondary prevention of in Type 2 diabetics coronary events without CHD; Reduces risk of MI, stroke, Reduces risk of coronary -- -- -- CHF hospitalization, revascularization angina, and revascularization in CHD patients Total-C = Total cholesterol; LDL-C = low density lipoprotein cholesterol; TG = triglycerides; ApoB = apoprotein B * Caduet is indicated when amlodipine and atorvastatin are both appropriate. Indications for amlodipine are hypertension, chronic stable angina, vasospastic angina, and angiographically documented coronary artery disease (CAD). Lipotropics, Statins Review – October 2020 Page 4 | Proprietary Information. Restricted Access – Do not disseminate or copy without approval. © 2004-2020 Magellan Rx Management. All Rights Reserved. FDA-Approved Indications (continued) rosuvastatin† pitavastatin pravastatin simvastatin Indications (Crestor, Ezallor (Livalo, Zypitamag)23 (Pravachol)24 (Flolipid, Zocor) 27,28 Sprinkle)25,26 Primary hypercholesterolemia . Heterozygous familial and nonfamilial X X X‡ X Reduce: Total-C, LDL-C, TG and ApoB Heterozygous familial hypercholesterolemia X X X‡ X . pediatric 8 years and older 8 years and older 8–17 years 10–17 years (Livalo only) Mixed dyslipidemia Fredrickson Type -- X X‡ X . IIa and IIb Reduce: Total-C, LDL-C, TG and ApoB Increase HDL-C X X X‡ X Hypertriglyceridemia - Fredrickson Type IV -- X X X Primary dysbetalipoproteinemia - Fredrickson Type III -- X X X Homozygous familial hypercholesterolemia X -- -- X 7–17 years§ Atherosclerosis -- X X‡ -- . slow progression CVD Reduces risk of MI, stroke, Reduces total mortality Reduces risk of MI, revascularization, in risk by reducing CHD . primary prevention of coronary events myocardial -- patients without clinically death, MI, stroke, and revascularization, CV evident CHD, but with need for revascularization mortality multiple risk factors‡ in high risk patients Total-C = Total cholesterol; LDL-C = low density lipoprotein cholesterol; TG = triglycerides; ApoB = apoprotein B † High risk = patients with increased risk of CV disease based on age 50 years (men) and 60 years (women), hsCRP 2 mg/dL, and presence of at least 1 additional CV risk factor (e.g., hypertension, low high-density lipoprotein cholesterol (HDL-C), smoking, or a family history of premature CAD). ‡ Approval for rosuvastatin (Crestor) only § Rosuvastatin (Ezallor Sprinkle) is approved for use in adults only. Lipotropics, Statins Review – October 2020 Page 5 | Proprietary Information. Restricted Access – Do not disseminate or copy without approval. © 2004-2020 Magellan Rx Management. All Rights Reserved. FDA-Approved Indications (continued) rosuvastatin† pitavastatin pravastatin simvastatin Indications (Crestor, Ezallor (Livalo, Zypitamag)29 (Pravachol)30 (Flolipid, Zocor) 33,34 Sprinkle)31,32 CHD Reduces risk of MI, Reduces total mortality myocardial risk by reducing CHD . secondary prevention of coronary events -- -- revascularization, CV death, MI, stroke, and mortality, stroke/TIA need for revascularization Total-C = Total cholesterol; LDL-C = low density lipoprotein cholesterol; TG = triglycerides; ApoB = apoprotein B † High risk = patients with increased risk of CV disease based on age 50 years (men) and 60 years (women), hsCRP 2 mg/dL, and presence of at least 1 additional CV risk factor (e.g., hypertension, low high-density lipoprotein cholesterol (HDL-C), smoking, or a family history of premature CAD). Lipotropics, Statins Review – October 2020 Page 6 | Proprietary Information. Restricted Access – Do not disseminate or copy without approval. © 2004-2020 Magellan Rx Management. All Rights Reserved. OVERVIEW Many clinical trials have demonstrated that a high serum concentration of low-density lipoprotein cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C) are major risk factors for coronary heart disease (CHD). The National Health and Nutrition Examination Survey (NHANES) reported that from 2015 to 2018, approximately 11.4% of adults in the United States (US) had high total cholesterol (≥ 240 mg/dL) and 17.2% had low HDL-C (< 40 mg/dL).35 The prevalence of high total cholesterol in women was 12.1% compared to 10.5% in men, but the difference was not significant. The prevalence of low HDL-C was higher in men (26.6%) compared to women (8.5%). In 2015 to 2018, there were no significant race and Hispanic-origin differences in the prevalence of high total cholesterol in adults. The NHANES analysis was based on measured cholesterol only and does not consider whether lipid-lowering medications were taken. In addition, NHANES
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  • Clinical Policy: Pitavastatin (Livalo), Ezetimibe/Simvastatin

    Clinical Policy: Pitavastatin (Livalo), Ezetimibe/Simvastatin

    Clinical Policy: Pitavastatin (Livalo), Ezetimibe/Simvastatin (Vytorin 10/10 mg) Reference Number: CP.CPA.62 Effective Date: 11.16.16 Last Review Date: 11.17 Revision Log Line of Business: Commercial See Important Reminder at the end of this policy for important regulatory and legal information. Description Pitavastatin (Livalo®) is an inhibitor of HMG-CoA reductase (statin) that lowers cholesterol in the blood for prevention of cardiovascular events and for the management of dyslipidemias. Ezetimibe/simvastatin (Vytorin®) is a combination cholesterol absorption inhibitor and HMG- CoA reductase inhibitor (statin). FDA approved indication Livalo: • Primary Hyperlipidemia or Mixed Dyslipidemia: As an adjunctive therapy to diet to reduce elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and to increase high density lipoprotein cholesterol (HDL-C) in adult patients with primary or mixed dyslipidemia. Vytorin: • Primary Hyperlipidemia: As an adjunctive therapy to diet to reduce elevated total-C, LDL- C, apo B, TG, and non-HDL-C, and to increase HDL-C in patients with primary (heterozygous familial and non-familial) hyperlipidemia or mixed hyperlipidemia. • Homozygous Familial Hypercholesterolemia (HoFH): As an adjunctive therapy to diet to reduce elevated total-C and LDL-C in patients with homozygous familial hypercholesterolemia (HoFH), as an adjunct to other lipid-lowering treatments. Limitations of use: • 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. • The effect of Livalo on cardiovascular morbidity and mortality has not been determined.