Subject:
Vivitrol® (Naltrexone Extended-Release) Injection
Description:
The FDA approved an injectable (intramuscular), long-acting form of naltrexone (Vivitrol®) in April 2006. Naltrexone is an opioid antagonist with the highest affinity for the mu opioid receptor; however, the neurobiological mechanism by which it reduces alcohol consumption in alcohol dependent patients is not entirely understood. Over the years, there have been a few oral agents such as Campral® (acamprosate calcium), Antabuse® (disulfiram), and Revia® (naltrexone hydrochloride) that have been used for alcohol dependence.
The efficacy of Vivitrol® was evaluated in a twenty-fourweek, placebo-controlled, multi-center, double-blind, randomized trial. Patients with a current diagnosis of alcohol dependence as defined by the Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition (DSM-IV) and average of 2 episodes of heavy drinking per week for the 30 days before randomization, were treated with an injection every 4 weeks of Vivitrol® 190 mg (n=210), Vivitrol(®) 380 mg (n = 205), or placebo (n=209), along with psychosocial support (12 sessions of low-intensity psychosocial support using Biopsychosocial, Report, Empathy, Needs, Direct advice, and Assessment Model- BRENDA). Standard drinks per day consumption was determined using the timeline follow back method, utilizing calendars and recall of drinking patterns, specifically data collected when breath alcohol levels were 0.02 g/dL or less. The group receiving Vivitrol® 380 mg demonstrated a statistically significant (P = 0.03) 25% reduction in heavy drinking days (≥ 5 standard drinks per day for men and ≥ 4 for women).
In October 2010, the FDA expanded the indication of Vivitrol® to include the prevention of relapse to opioid dependence, following opioid detoxification.
The efficacy of Vivitrol in the treatment of opioid dependence was evaluated in a 24 week, placebo-controlled, multi-center,double-blind, randomized trial of opioid-dependent outpatients, who had or were completing detoxification. The percentage of subjects achieving observed percentages of opioid-free weeks was greater in the Vivitrol group compared to the placebo group. Complete abstinence was observed in 23% of subjects in the placebo group compared with 36% of subjects in the Vivitrol group from Week 5 to Week 24.
Policy:
[INFORMATIONAL NOTE: Pursuant to the New Jersey State Mandate on substance use disorder (P.L.2017, c.28, effective May 16, 2017), health benefit plans are required to provide unlimited benefits for medically necessary inpatient (IP) and outpatient (OP) treatment of substance use disorder at in-network facilities and from in-network providers. It also prohibits any prior authorization or prospective utilization management for the first 180 days per plan year of medically necessary IP and OP treatment of substance use disorder, i In addition, it places restrictions on prescription of opioids, such as a 5-day supply limit on initial prescriptions for treatment of acute pain.
For additional information and specific provisions, please refer to the mandate. Not applicable to Medicare Advantage Products. ]
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
1. Vivitrol® (naltrexone extended-release) injection is medically necessary for the FDA-approved indication of the treatment of alcohol dependence in members who meet ALL of the following:
- Able to abstain from alcohol in an outpatient setting prior to initiation of treatment
- Not actively drinking at the time of Vivitrol® administration
- Enrolled in a comprehensive management program that includes psychosocial support (eg. Alcoholics Anonymous)
[ INFORMATIONAL NOTE: The inclusion and exclusion criteria of the pivotal twenty-four week placebo-controlled, multi-center, double-blind, randomized trial are as follows:
Inclusion criteria:
- 18 years or older with a current diagnosis of alcohol dependence defined by DSM-IV with minimum of 2 episodes of heavy drinking (≥5 standard drinks/day for men and ≥4 standard drinks/day for women) per week during the 30 days before screening.
Exclusion criteria:
- Evidence of liver failure
- Major depression with suicidal ideation, psychosis or bipolar disorder
- Dependence within the past year on benzodiazepines, opiates or cocaine
- More than 7 days of inpatient treatment for substance abuse in the month before screening
- Use of opiates, oral naltrexone, or disufiram in the 2 weeks before screening.
All patients received 12 sessions of standardized supportive therapy using BRENDA model that were administered by psychologists, nurses, therapists, counselors and physicians at study sites.
A subpopulation of fifty-three lead-in abstinent patients (8.8%), defined as those who reported no drinking during the consecutive 7 days preceding the first dose of study medication, were included in the study analysis. It was found that treatment effects were greater for patients with lead-in abstinence (HR, 0.20, P = .005) compared with patients who drank during the lead-in period (HR, 0.79,P = .05).]
2. Vivitrol® (naltrexone extended-release) injection is medically necessary for the FDA-approved indication of the prevention of relapse to opioid dependence following opioid detoxification.
3. Vivitrol® is contraindicated or not considered medically necessary in the following instances for members:
· Member receiving opioid analgesics
· Member with current physiologic opioid dependence
· Member is in acute opiate withdrawal
· Member failed the naloxone challenge test or has a positive urine screen for opioids
· Member has previously exhibited hypersensitivity to naltrexone, polylactid-co-glycolide (PLG), carboxymethycellulose, or any other components of the diluent.
4. Vivitrol® is approved initially for 6 months at the FDA approved dose of 380 mg (1 vial) delivered intramuscularly every 4 weeks.
[INFORMATIONAL NOTE: According to the FDA approved package insert, the injection must be administered by a healthcare professional as an intramuscular (IM) gluteal injection, alternating buttocks for each subsequent injection, using the carton components provided. Vivitrol must not be administered intravenously or subcutaneously. FDA informed healthcare professionals of the risk of adverse injection site reactions in patients receiving naltrexone. As per the FDA approved package insert, to prevent occurrence of an acute abstinence (withdrawal) in patients dependent on opioids, or an exacerbation of a pre-existing subclinical abstinence syndrome, patients must be opioid-free for a minimum of 7-10 days before starting Vivitrol® treatment.]
5. Continued therapy with Vivitrol® will be considered for an additional 6 months beyond the initial approval period:
· If the member shows reduction in heavy drinking when used for alcohol dependence.
[INFORMATIONAL NOTE: As per the Center for Disease Control and Prevention, a standard drink is one 12 oz. beer, 5 oz. of wine, 1.5 oz. of 80-proof spirits, or 8 oz. of malt liquor.]
· If the member shows sustained abstinence from opioid use when used for the prevention of relapse to opioid dependence
[INFORMATIONAL NOTE: Methods to determine opioid use include the naloxone challenge test and urine screen for opioids]
6. Continued therapy beyond 12 months will be reviewed on a case-by-case basis every 6 months based on the member's response to drug therapy and continued enrollment in a comprehensive management program which includes psychosocial support.
7. Other uses of Vivitrol® are considered investigational, including but not limited to, amphetamine dependence, cocaine dependence, Crohn’s disease, cannabis dependence, treatment resistant depression (TRD), hypoglycemia. Alzheimer's disease, schizophrenic disorder.
Medicare Coverage
There is no National Coverage Determination (NCD). In the absence of an NCD, coverage decisions are left to the discretion of Local Medicare Carriers. Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, has not issued a determination for this service. Therefore, Medicare Advantage Products will follow the Horizon Policy.
Medicaid Coverage
For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf
Index:
Vivitrol® (Naltrexone Extended-Release) Injection
Naltrexone-Extended Release Injection (Vivitrol)
References:
1. Vivitrol® product information. Alkermes. Cambridge, MA. September 2019.
2. FDA Update: Naltrexone for extended-release injectable suspension Information. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm103334.htm
3. Naltrexone (Vivitrol)- A Once-Monthly injection for Alcoholism. The Medical Letter on Drugs and Therapeutics. 2006 July 21;48(1240): 53-65.
4. US Department of Health and Human Services. Naltrexone and alcoholism treatment: Treatment improvement protocol (TIP) Series 28. Available at: http://ncadi.samhsa.gov/govpubs/bkd268/28c.aspx. Accessed 3/2011.
5. Garbutt J, et al. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence. JAMA 2005; 293:1617-1625.
6. American Heart Association. Alcohol, Wine and Cardiovascular Disease. Available from: http://www.americanheart.org/presenter.jhtml?identifier=4422
7. Center for Disease Control and Prevention. Alcohol and Public Health-FAQs. Available from: http://www.cdc.gov/alcohol/faqs.htm#4
8. US Department of Agriculture. Dietary Guidelines for Americans 2010. Available from: http://www.health.gov/dietaryguidelines/dga2010/DietaryGuidelines2010.pdf.
9. Clinical Trials.gov. Study of Naltrexone for Methamphetamine Addiction. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00984360?term=vivitrol&rank=43.
10. Clinical Trials.gov. Extended Release Naltrexone for Treating Amphetamine Dependence in Iceland. Available from: http://www.clinicaltrials.gov/ct2/show/NCT01100853?term=vivitrol&rank=9.
11. Clinical Trials.gov. Vivitrol as a Treatment for Cocaine and Alcohol Dependence. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00777062?term=vivitrol&rank=10.
12. ClinicalTrials.gov. Vivitrol as Treatment for Treatment Resistant Depression Available from: https://clinicaltrials.gov/ct2/show/NCT02911597
13. ClinicalTrials.gov. Vivitrol as Treatment for Cannabis Dependence Available from: https://clinicaltrials.gov/ct2/show/NCT02088177
14. ClinicalTrials.gov. Vivitrol. Available at: https://clinicaltrials.gov/ct2/results?cond=vivitrol&term=&cntry=&state=&city=&dist= . Accessed January 2020.
15. Clinical Pharmacology. Vivitrol. Available at: https://www.clinicalkey.com/pharmacology/monograph/426?sec=monindi&n=Vivitrol. Accessed February 4, 2020.
16. Drugdex. Vivitrol. Dosing/Administration. Non-FDA uses. Accessed February 4, 2020.
17. AHFS. Vivitrol. Other uses. Available at: http://online.statref.com/document/ve1xLQ2CZKvg9FkYolk6ej!!?searchid=1580846335060585510&categoryType=All. Accessed February 4, 2020.
Codes:
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CPT*
HCPCS
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