CLINICAL POLICY Department: Medical Management Document Name: Vivitrol Reference Number: NH.PHAR.96 Effective Date: 03/12



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Page: 1 of 7 IMPORTANT REMINDER This Clinical Policy has been developed by appropriately experienced and licensed health care professionals based on a thorough review and consideration of generally accepted standards of medical practice, peer-reviewed medical literature, government agency/program approval status, and other indicia of medical necessity. The purpose of this Clinical Policy is to provide a guide to medical necessity. Benefit determinations should be based in all cases on the applicable contract provisions governing plan benefits ( Benefit Plan Contract ) and applicable state and federal requirements, as well as applicable plan-level administrative policies and procedures. To the extent there are any conflicts between this Clinical Policy and the Benefit Plan Contract provisions, the Benefit Plan Contract provisions will control. Clinical policies are intended to be reflective of current scientific research and clinical thinking. This Clinical Policy is not intended to dictate to providers how to practice medicine, nor does it constitute a contract or guarantee regarding payment or results. 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. Subject Medical necessity criteria for Vivitrol (naltrexone for extended-release injectable suspension) Description The intent of the criteria is to ensure that patients follow selection elements established by Centene medical policy for Vivitrol. FDA-Approved Indications Alcohol Dependence Vivitrol is indicated for the treatment of alcohol dependence in patients who are able to abstain from alcohol in an outpatient setting prior to initiation of treatment with Vivitrol. 1 Patient should not be actively drinking at the time of initial Vivitrol administration. Opioid Dependence Vivitrol is indicated for the prevention of relapse to opioid dependence, following opioid detoxification. 1 Policy/Criteria It is the policy of health plans affiliated with Centene Corporation that Vivitrol is medically necessary for members who meet the following algorithm criteria: Figure 1: Vivitrol Safety Algorithm Figure 2: Vivitrol Alcohol Dependence Algorithm Figure 3: Vivitrol Opioid Dependence Algorithm

Page: 2 of 7 Figure 1: Vivitrol Safety Algorithm Acute hepatitis or liver failure? experiencing acute opioid withdrawal or physically dependent to opioids? Had a naloxone challenge test or urine screen for opioids within last 7 days? Document result of UDS or naloxone challenge Positive for opioids? Anticipated need for opioid pain meds during Vivitrol therapy? What is intent of treatment? Prevention of relapse to opioid dependence Other Treatment of alcohol dependence Proceed to Figure 3 Proceed to Figure 2

Page: 3 of 7 Figure 2: Vivitrol Alcohol Dependence Algorithm From Figure 1 abstaining from alcohol? receiving Vivitrol injection? participating or will participate in alcohol counseling and AA? Tried and failed oral naltrexone? Had at least 6 months of sobriety or received at least 6 months of Vivitrol injection? Adherent to Vivitrol injection? Approve for 3 months participating in alcohol counseling and AA?

Page: 4 of 7 Figure 3: Vivitrol Opioid Dependence Algorithm From Figure 1 receiving Vivitrol through Centene benefit? Tried and failed Suboxone? Tried and failed oral naltrexone? on Vivitrol therapy? How long has the patient been on Vivitrol injection? 1 year <1 year participating or will participate in drug abuse counseling? Adherent to Vivitrol injection? Approve for 3 months participating in drug abuse counseling?

Page: 5 of 7 Background Vivitrol (naltrexone) is an opioid antagonist with a high affinity for the mu opioid receptors indicated for the treatment of alcohol dependence and for the prevention of relapse to opioid dependence. 1 Mu opioid receptors play a major role in developing alcohol and opioid dependence through their rewarding effects. 2,3 Because substance abuses are highly prevalent and its health, social, and economic consequences are usually devastating, diverse treatment options are needed, including psychosocial approaches and pharmacological treatment. 4 Naltrexone produces antagonistic effects by competitively displacing opiate molecules at opiate receptors as well as by blocking the access of narcotics to opiate receptor sites. 5 In alcohol dependence, naltrexone, by blocking opioid receptors, leads to less alcohol-induced pleasure, high, and intoxication, and ultimately, less craving and relapse. In opioid dependence, it is thought that naltrexone may diminish or eliminate opiate-seeking behavior by blocking the euphoriant effect of opiates. 5,6 In addition to Vivitrol, there are orally-administered therapies available for the management of alcohol and opioid dependence. For alcohol dependence, the available therapies include naltrexone, acamprosate, and disulfiram. 5-9 These medications may help patients reduce drinking, avoid relapse to heavy drinking, achieve and maintain abstinence, or gain a combination of these effects. 7-9 If one medication proves ineffective for an individual, another may be tried. 7,8 For opioid dependence, naltrexone is available in tablet form and works in the same manner as Vivitrol injection. 5,6 Both are effective in preventing relapse in patients who have withdrawn from opioids. 10 Additional therapies for opioid dependence include maintenance therapy with an opioid agonist such as methadone and buprenorphine. 9,10 Regardless of the pharmacological therapy selected, drug therapy should be a part of a comprehensive management program that includes psychosocial support or counseling. 7-10 It is noted that when pharmacologic therapy is used in conjunction with a comprehensive management program, the benefits of such programs may be additive or prolonged. 6,10 Safety WARNING: HEPATOTOXICITY 1 Cases of hepatitis and clinically significant liver dysfunction were observed with Vivitrol exposure during the clinical development program and in post marketing period. Transient, asymptomatic hepatic tranaminase evelavatons were also observed in the clinical trails and post marketing period. Although patients with clinically significant liver disease were not systematically studied, clinical trials did include patients with asymptomatic viral hepatitis infections. When patients presented with elevated transaminases, there were often other potential causative or contributory etiologies identified, including pre-existing alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other potentially hepatotoxic drugs.

Page: 6 of 7 Patients should be warned of the risk of hepatic injury and advised to seek medical attention if they experience symptoms of acute hepatitis. Use of Vivitrol should be discontinued in the event of symptoms and/or signs of acute hepatitis. Vivitrol is contraindicated in the following patients: 1) patients with acute hepatitis or liver failure, 2) patients receiving opioid analgesics, 3) patients with current physiologic opioid dependence, 4) patients in acute opioid withdrawal, 5) patients who have failed the naloxone challenge test or have a positive urine screen for opioids, and 6) patients who have previously exhibited hypersensitivity to naltrexone, polylactide-co-glycolide, carboxymethylcellulose, or any other components of the diluent. 1 Prior to initiating Vivitrol, both opioid-dependent and alcohol dependent patients must be free of opioids. References 1. Vivitrol [naltrexone for extended-release injectable suspension). Waltham, MA. Alkermes, Inc.; July 2013. 2. Mendez M, Morales-Mulia M. Role of mu and delta opioid receptors in alcohol drinking behavior. Curr Drug Abuse Rev. 2008 Jun;1(2):239-252. 3. Le Merrer J, Becker JA, Befort K, et al. Reward processing by the opioid system in the brain. Physiol Rev. 2009 Oct;89(4):1379-1412. 4. World Health Organization. Management of Substance Dependence. A Systematic Review of Opioid Antagonists for Alcohol Dependence. http://www.who.int/substance_abuse/publications/en/opioid.pdf. Accessed August 8, 2011. 5. Naltrexone. In: DRUGDEX System [Internet database]. Ann Arbor, MI, USA: Truven Health Analytics. Updated periodically. Available at: http://www.thomsonhc.com. 6. American Society of Health System Pharmacists. AHFS Drug Information. Bethesda, MD. Electronic version, 2011. http://online.lexi.com. 7. Prescribing Medications for Alcohol Dependence - Excerpt from Helping Patients Who Drink Too Much: A Clinician s Guide. U.S. Department of Health and Human Services, National Institutes of Health National Institute on Alcohol Abuse and Alcoholism. NIH Publication 07 3769. October 2008 Update. http://pubs.niaaa.nih.gov/publications/practitioner/cliniciansguide2005/prescribingmeds.pdf. 8. Helping Patients Who Drink Too Much: A Clinician s Guide. U.S. Department of Health and Human Services, National Institutes of Health National Institute on Alcohol Abuse and Alcoholism. NIH Publication 07 3769 (Updated 2005 Edition). www.niaaa.nih.gov/guide. 9. Kleber, HD, Weiss RD, Anton RF Jr, et al. Treatment of patients with substance use disorders, second edition. American Psychiatric Association. Am J Psychiatry. 2007;164(4 Suppl):5-123. 10. World Health Organization. Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence. http://www.who.int/substance_abuse/publications/opioid_dependence_guidelines.pdf.

Page: 7 of 7 Revision Log Date Removed the two questions related to hepatitis warnings in Figure 1: 03/13 Has the patient been warned about the risk of hepatic injury and been advised to seek medical attention if they experience symptoms of acute hepatitis? Will Vivitrol be discontinued in the event of symptoms or signs of acute hepatitis? Converted to Centene policy template 06/13 Reviewed with no changes recommended 03/14 Reversed references to figure 2 & 3 in Figure 1 (incorrectly directed) 08/14 Edited Warning: Hepatotoxicity 02/15 Updated references Added requirement for drug screen within last 7 days. Added requirement for patients to try and fail oral naltrexone. Added requirement of recent drug screening for reauthorization. Removed requirement for monthly drug screen 07/15 2014 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. 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.