Commercial

Medical Policy

Notification

Maintenance Treatment of Opioid or Alcohol Use Disorder

Notification Issue Date:

This version of the policy will become effective 01/01/2023.

This policy has been updated to include the Company's coverage position on methadone maintenance therapy as Medically Necessary with criteria.

The following changes have been made from the previous version:

The Company's coverage position was updated to include methadone maintenance therapy as Medically Necessary with criteria.
The requirement Individual participates in a comprehensive treatment program, which includes counseling and psychosocial support has been removed under BUPRENORPHINE (PROBUPHINE®) IMPLANTS and BUPRENORPHINE (SUBLOCADE^TM) INJECTION.
The requirement Individual has shown compliance with scheduled and random urine drug screening has been removed under BUPRENORPHINE (SUBLOCADE^TM) INJECTION.
Updates to ICD-10 diagnosis codes.

Title:

Maintenance Treatment of Opioid or Alcohol Use Disorder

Policy #:

08.01.37f

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

METHADONE

Methadone maintenance therapy is considered medically necessary and, therefore, covered for individuals with opioid use disorder (OUD)* when all of the following criteria are met:

The individual is diagnosed with moderate or severe OUD (including moderate or severe OUD in remission), or be at high risk of recurrence or overdose.
The individual is free of an urgent or emergent medical or psychiatric problem(s).
One of the following:

The individual is 18 years of age or older and is able to give informed consent.
For individuals less than 18 years of age consent of a parent or legal guardian has been given (Except in States where State law grants persons under 18 years of age the ability to consent to OTP treatment without the consent of another)

There is documentation that the professional provider is certified by the Substance Abuse and Mental Health Services Administration (SAMHSA).
The professional provider attests that the member cannot be treated safely or effectively in a level of care less intensive than an opioid treatment program (OTP).
The individual will receive counseling or psychotherapy

*Methadone for OUD must be dispensed in a licensed OTP that adheres to all federal guidelines.

BUPRENORPHINE (SUBLOCADE^TM) INJECTION
Buprenorphine (Sublocade) extended-release subcutaneous injection administered monthly (with a minimum of 26 days between doses) is considered medically necessary and, therefore, covered for the treatment of moderate to severe OUD when all of the following criteria are met:

The individual has a documented diagnosis of an OUD, as per DSM-5 TR.
The individual has initiated treatment with a transmucosal buprenorphine-containing product delivering the equivalent of 8 to 24 mg of buprenorphine daily, followed by dose adjustment for a minimum of 7 days. The individual is clinically stable on this dose.
The individual is not concurrently receiving supplemental dosing with buprenorphine products.

Continuation of Therapy with Buprenorphine (Sublocade) Injection

If continued therapy is required, buprenorphine (Sublocade) injection is considered medically necessary and, therefore, covered when the above criteria have been met.

Provider Requirements

Providers must be in compliance with all of the criteria outlined in the REMS program.

Prescribers must have qualifications that include a current, valid state medical license.

NALTREXONE (VIVITROL®) INJECTION
Alcohol Use Disorder

Naltrexone (Vivitrol®) intramuscular (IM) injection administered every 4 weeks (or monthly) is considered medically necessary and, therefore, covered for the treatment of alcohol dependence in individuals able to abstain from alcohol when all of the following criteria are met:

The individual has a documented diagnosis of alcohol use disorder, as per (DSM-5-TR)
The individual has abstained from alcohol prior to naltrexone (Vivitrol®) administration

Continuation of Therapy with Naltrexone (Vivitrol)
If continued therapy is required, naltrexone (Vivitrol) is considered medically necessary and, therefore, covered when the above criteria have been met.

Opioid Use Disorder

Naltrexone (Vivitrol) intramuscular (IM) injection administered every 4 weeks (or monthly) is considered medically necessary and, therefore, covered for the prevention of relapse to opioid dependence (following opioid detoxification) when all of the following criteria are met:

The individual has a documented diagnosis of OUD, as per (DSM-5-TR).
The individual has abstained from opioids at least 7 to 10 days prior to and on the day of naltrexone (Vivitrol) administration.

Continuation of Therapy with Naltrexone (Vivitrol)
If continued therapy is required, naltrexone (Vivitrol) is considered medically necessary and, therefore, covered when the above criteria have been met.

EXPERIMENTAL/INVESTIGATIONAL

All other uses than those described above for buprenorphine (Sublocade) injection are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

All other uses than those described above for naltrexone (Vivitrol) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics. Examples of uses considered experimental/investigational include, but are not limited to the following:

The individual is receiving opioid analgesics.
The individual currently has physiologic opioid or alcohol dependence, including the use of partial agonists.
The individual is in acute opioid or alcohol withdrawal.
The individual has failed the naloxone challenge or has a positive urine screen for opioids.

Naltrexone implants are considered experimental/investigational and, therefore, not covered because the safety and/or effectiveness of this service cannot be established by review of the available published peer-reviewed literature.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

Guidelines

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

DRUG ADMINISTRATION

The following information was derived from the US Food and Drug Administration (FDA)–approved prescribing information:

BUPRENORPHINE (SUBLOCADE) INJECTION
The following information was derived from the FDA-approved prescribing information:

Individuals appropriate for buprenorphine (Sublocade) are adults who have initiated treatment on a transmucosal buprenorphine–containing product delivering the equivalent of 8 to 24 mg of buprenorphine daily. The individual may only be transitioned to buprenorphine (Sublocade) after a minimum of 7 days.

Initiation of treatment with transmucosal buprenorphine–containing products should be based on instructions in their appropriate product label. One buprenorphine and naloxone (Suboxone) 8 mg/2 mg sublingual tablet provides equivalent buprenorphine (Sublocade) exposure to:

One buprenorphine (Subutex) 8 mg sublingual tablet, or
One buprenorphine and naloxone (Bunavail) 4.2mg/0.7 mg buccal film, or
One buprenorphine and naloxone (Zubsolv) 5.7 mg/1.4 mg sublingual tablet

Buprenorphine (Sublocade) is only approved for subcutaneous injection. Serious harm or death could result if administered intravenously. Buprenorphine (Sublocade) injection forms a solid mass upon contact with body fluids and may cause occlusion, local tissue damage, and thromboembolic events, including life-threatening pulmonary emboli, if administered intravenously.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, buprenorphine (Sublocade), and naltrexone (Vivitrol) are covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

Subject to the terms and conditions of the applicable benefit contract, naltrexone (Vivitrol) implants are not eligible for payment under the medical benefits of the Company’s products because the service is considered experimental/investigational and, therefore, not covered.

Services that are experimental/investigational are a benefit contract exclusion for all products of the Company. Therefore, they are not eligible for reimbursement consideration.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Buprenorphine (Sublocade) was approved by the FDA on November 30, 2017, for the treatment of moderate to severe opioid use disorder in individuals who have initiated treatment with a transmucosal buprenorphine–containing product, followed by dose adjustment for a minimum of 7 days.

Naltrexone (Vivitrol) implants are compounded implantable pellets that are not approved by the FDA.

Naltrexone (Vivitrol) was approved by the FDA on April 30, 2006, for the treatment of alcohol dependence in individuals who are able to abstain from alcohol in an outpatient setting prior to initiation of treatment with naltrexone (Vivitrol). Supplemental approvals for naltrexone (Vivitrol) have since been issued by the FDA.

PEDIATRIC USE

The safety and effectiveness of buprenorphine (Sublocade) have not been established in children.

The safety, efficacy, and pharmacokinetics of naltrexone (Vivitrol) have not been established in the pediatric population.

Description

OVERVIEW

The American Society of Addiction Medicine (ASAM) describes the impact of opioid use disorder as a chronic, relapsing disease that has significant economic, personal, and public health consequences. ASAM has reported that drug overdose is a national epidemic and is the leading cause of accidental death in the United States.

According to the Behavioral Health Trends in the United States: Results from the 2021 National Survey on Drug Use and Health (NSDUH) Results Detailing Mental Illness and Substance Use Levels, published by the Substance Abuse and Mental Health Services Administration (SAMHSA), in 2021:

61.2 million individuals aged 12 years or older (21.9 percent of this population) used illicit drugs
52.5 million individuals used marijuana, which was the most commonly used illicit drug (one in three individuals aged 18 to 25 years used marijuana)
Close to two in five individuals 18 to 25 years old used illicit drugs
9.2 million individuals aged 12 years or older misused opioids
46.3 million individuals aged 12 years or older (16.5 percent of the population) met DSM-5-TR criteria for substance use disorder (compared with 21.5 million individuals in 2014)
29.5 million individuals met criteria for alcohol use disorder (an increase from 17 million individuals in 2014)
24 million individuals met criteria for drug use disorder (an increase from 7.1 million individuals in 2014)
Alcohol use disorder and drug use disorder were highest among individuals aged 18 to 25 years, compared with those younger than 18 years and those 26 years and older
Among individuals aged 12 years and older, 94% received no treatment; among individuals who did not receive treatment at a specialty facility, almost none believed they required treatment

Opioid and alcohol use disorders are initially treated with psychosocial support, counseling, and pharmacologic agents (oral or sublingual agents). Those unable to comply with daily dosing may be able to transition to longer acting agents. Once the individual is stabilized on the appropriate dose, they may be transitioned to longer acting drugs, such as buprenorphine (Sublocade) subcutaneous injection, or naltrexone (Vivitrol) intramuscular (IM) injection. These drugs are used as a part of a comprehensive treatment program that includes psychosocial support and counseling.

BUPRENORPHINE (SUBLOCADE) INJECTION

Buprenorphine is a Schedule III controlled substance and a partial agonist at the mu-opioid receptor. Buprenorphine has low intrinsic activity, so when it binds to the mu-opioid receptors, it activates the receptors to a lesser degree than full agonists (e.g., morphine, heroin, methadone) causing a lower potential for opioid effects, such as euphoria or sedation. Because buprenorphine has a high affinity for receptors, it cannot be displaced by full agonists; it also displaces full agonists already bound to receptors. Buprenorphine produces a physical dependence on the drug and also has a high potential for abuse that can result in overdose or death; these risks increase when individuals are also receiving other drugs that act on the central nervous system, such as benzodiazepines or alcohol. As an US Food and Drug Administration (FDA)-classified Schedule III controlled substance, there is potential for abuse, dependence, overdose, and death.

The Drug Addiction Treatment Act of 2000 (DATA 2000) permits the prescribing and dispensing of certain narcotic schedule III, IV, or V medications, such as buprenorphine to be used as opioid replacement therapy in an office- or clinic-based setting. The provider must apply for a waiver and receive additional training. Qualifications for a DATA 2000 waiver include a current, valid state medical license and a unique drug enforcement agency (DEA) registration number. Furthermore, the provider must meet at least one criteria outlined by the US Department of Health and Human Services, Substance Abuse, and Mental Health Services Administration, where the provider must have certain credentials/training in the treatment of addiction.

Any professional provider can prescribe/insert/remove the implants, as long as the appropriate licensure is held and relevant training is obtained. Examples of provider types may include Addiction Psychiatrists, Board-Certified Addiction Specialists, Primary Care Providers, etc.

BUPRENORPHINE (SUBLOCADE) INJECTION
Buprenorphine (Sublocade) subcutaneous injection was approved by the FDA on November 30, 2017, for the treatment of moderate to severe opioid use disorder in individuals who have initiated treatment with a transmucosal buprenorphine–containing product, followed by dose adjustment for a minimum of 7 days. Buprenorphine (Sublocade) is administered subcutaneously into the abdomen by a professional provider as a monthly dose with a minimum of 26 days between doses.

The FDA initiated a REMS program due to the risk of serious harm or death that could result from intravenous self-administration. The goal of the REMS is to mitigate serious harm or death that could result from intravenous self-administration by ensuring that healthcare settings and pharmacies are certified and only dispense buprenorphine (Sublocade) directly to a healthcare provider for administration by a healthcare provider. Components of the REMS program include:

Healthcare Settings and Pharmacies that order and dispense buprenorphine (Sublocade) must be certified in the SUBLOCADE REMS Program
Certified Healthcare Settings and Pharmacies must establish processes and procedures to verify that buprenorphine (Sublocade) is provided directly to a healthcare provider for administration by a healthcare provider, and the drug is not dispensed to the individual
Certified Healthcare Settings and Pharmacies must not distribute, transfer, loan, or sell buprenorphine (Sublocade)

Peer-Reviewed Literature for Buprenorphine (Sublocade) Injection

Summary
The safety and effectiveness of buprenorphine (Sublocade) injection was established in a Phase 3 randomized, double-blind, placebo-controlled multicenter trial over a 24-week period in treatment-seeking individuals (N=504) who met the DSM-5-TR criteria for moderate or severe opioid use disorder. All participants were stabilized on buprenorphine/naloxone sublingual film prior to the first dose, and received psychosocial support in addition to one of the following dosing arms: six once-monthly 300-mg doses, two once-monthly 300-mg doses followed by 4 once-monthly 100 mg doses, or 6 once-monthly SC injections of placebo (randomized 4:4:1:1 [203 subjects in the 300 mg/100 mg group, 201 subjects in the 300 mg/300 mg group, and 100 subjects in the placebo group [two groups of volume-matched placebo)]. The primary efficacy endpoint was the cumulative distribution function (CDF) of the percentage of opioid-free weeks at Week 24 based on weekly urine drug screens combined with self-reported use of illicit opioid use. It was determined, regardless of dose, that buprenorphine (Sublocade) was superior to the placebo group with statistical significance.

The number of participants with 80% or more opioid-free weeks was statistically significantly higher in both groups receiving buprenorphine (Sublocade) compared to the placebo group (28.4% [300 mg/100 mg], 29.1% [300 mg/300mg], 2% [placebo]).

NALTREXONE IMPLANTS AND (VIVITROL) INJECTION

Naltrexone is an opioid antagonist that binds to and blocks the mu-opioid receptor, thereby preventing the receptor from being activated by full agonists, such as morphine, heroin, and methadone. Without activation of the receptor, there are no opioid effects such as euphoria or sedation.

NALTREXONE IMPLANTS
Naltrexone implants are compounded pellets using a bulk powder formulation of naltrexone. As per FDA guidance, "Compounded drugs are not FDA-approved. This means that FDA does not review these drugs to evaluate their safety, effectiveness, or quality before they reach patients." Although there have been randomized trials and systematic reviews for naltrexone implants, the evidence is limited in quantity and quality.

Peer-Reviewed Literature for Naltrexone Implants

Summary
The National Health and Medical Research Council (NHMRC) guidance on the use of naltrexone implant in 2010 concluded that "while naltrexone implant treatment may show some efficacy as part of an integrated program, more research is needed. Naltrexone implants are an experimental product and as such should only be used in the context of a well-conducted randomized controlled trial with sufficient sample size, appropriate duration of treatment and follow up, regular robust monitoring, provision of a comprehensive psychosocial treatment program, and with comparison to current best practice. Until these trials have occurred and the relevant data are available and validated, the efficacy of the treatment, alone or in comparison to conventional first line treatments, cannot be determined."

As summarized in The World Federation of Societies of Biological Psychiatry guidelines, the majority of evidence for naltrexone implants have been trials in countries outside of the United States, including Russia and Australia. They stated "naltrexone implants cannot yet be recommended for clinical use because although there are promising efficacy data for them, safety concerns remain and require further evaluation" (Soyka et al. 2011).

In 2012, Krupitsky et al. conducted a randomized, double-dummy, double-blind, 24-week trial in 306 individuals in Russia. There were three study arms to compare efficacy:

bimonthly naltrexone implant and daily oral placebo
bimonthly placebo implant and daily oral naltrexone
bimonthly placebo implant and daily oral placebo

The primary outcome was retention without relapse. At 6 months, those with the naltrexone implant (52.9%) remained in treatment without relapse, compared to oral naltrexone (15.7%) or placebo (10.8%) at 6 months; however, there was loss to follow-up at 9 and 12 months. Longer term studies are required in order to make final efficacy determinations.

A systematic review and meta-analysis was performed by Larney et al. in 2014. Five randomized controlled trials (576 individuals) and four non-randomized studies (8358 individuals) were included in the review. The quality of evidence reviewed was classified as moderate to low. They summarized that “The evidence on safety, efficacy, and effectiveness of naltrexone implants was limited in quantity and quality, and the evidence had little clinical use in settings where effective treatments for opioid dependence (such as opioid substitution therapy) were available. Naltrexone implants were significantly more effective in suppressing opioid use than placebo or oral naltrexone.”

Kelty et al. in 2017 conducted a retrospective cohort study in Australia to compare rates of fatal and serious but nonfatal opioid overdose in opioid-dependent individuals treated with methadone, buprenorphine or implant naltrexone, and to identify risk factors for fatal opioid overdose. They reviewed opioid-dependent individuals treated with methadone (n = 3515), buprenorphine (n = 3250) or implant naltrexone (n = 1461) between 2001 and 2010, were matched against state mortality and hospital data. They concluded there was no significant difference between the three groups in terms of crude rates of fatal or nonfatal opioid overdoses.

NALTREXONE (VIVITROL) INJECTION
Naltrexone (Vivitrol) was approved by the FDA on April 13, 2006, for the treatment of alcohol dependence in individuals who are able to abstain from alcohol in an outpatient setting prior to initiation of treatment with naltrexone (Vivitrol). In addition, on October 12, 2010, naltrexone (Vivitrol) was FDA-approved for the prevention of relapse to opioid dependence, following opioid detoxification.

Naltrexone (Vivitrol) is available as one 380-mg vial that may be administered by a professional provider (no special training is required) via IM gluteal injection (alternating buttocks for each subsequent injection) every 4 weeks or once a month. Prior to initiating naltrexone (Vivitrol), an opioid-free duration of a minimum of 7 to 10 days is recommended for individuals, to avoid precipitation of opioid withdrawal that may be severe enough to require hospitalization.

The FDA initiated a REMS program for naltrexone (Vivitrol) to inform professional providers about the potential risk of severe injection site reactions that may occur during administration and to, additionally, counsel their patients accordingly. The communication includes a patient counseling tool and a poster that shows professional providers the “Key Techniques to Reduce Severe Injection Site Reactions.”

Peer-Reviewed Literature for Naltrexone (Vivitrol) Injection

Summary

Garbutt et al. in 2005 evaluated the efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence in a 6-month, randomized, double-blind, multicenter, placebo-controlled trial. Participants received monthly IM injections of 380 mg of long-acting naltrexone (n=205), 190 mg of long-acting naltrexone (n=210), or a matching volume of placebo (n=209), along with biweekly psychosocial support.

The primary efficacy endpoint was the event rate, which combines the frequency and pattern of heavy drinking days over the 24 weeks of treatment. The definition of heavy drinking (five or more drinks per day for men and four or more drinks per day for women). Participants who received 380 mg of long-acting naltrexone experienced approximately a 25% greater reduction in the rate of heavy drinking relative to placebo-treated individuals (P=0.03). Individuals treated with naltrexone 190 mg reported a 17% greater reduction in the rate of heavy drinking than placebo-treated individuals (P=0.07). A subset of individuals with lead-in abstinence showed even greater reductions in the number of drinking days and in the number of heavy drinking days, when receiving long-acting naltrexone, compared to placebo-treated individuals. These results were not seen in the subset of individuals who were actively drinking at the time of treatment initiation. Long-acting injectable naltrexone was well tolerated, where the most common adverse events were nausea, headache, fatigue, and injection site reaction tenderness.

Krupitsky et al. 2011 performed a double-blind, placebo-controlled, multicenter randomized (1:1) trial to evaluate the safety and effectiveness of injectable extended-release naltrexone (n=126) versus placebo (n=124) for the treatment of opioid dependence. Placebo or injectable extended-release naltrexone were administered at 380 mg IM every 4 weeks for 24 weeks, along with biweekly individual drug counseling sessions. After 24 weeks, all participants were offered open-label injectable extended-release naltrexone for an additional year. The primary endpoint was the response profile for confirmed abstinence during weeks 5 to 24, assessed by urine drug tests and self report of non-use. The median proportion of weeks of confirmed abstinence was 90% in the injectable extended-release naltrexone group compared with 35% in the placebo group (P=0.0002). Individuals in the injectable extended-release naltrexone group self-reported a median of 99.2% opioid-free days compared with 60.4% for the placebo group (P=0.0004). Total abstinence (opioid-free at all weekly visits) was reported in 36% of individuals in the injectable extended-release naltrexone group compared with 23% in the placebo group (P=0.0224). According to the authors, injectable extended-release naltrexone was well-tolerated with mainly mild to moderate adverse reactions.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

References for Medically Necessary Indications

Aronowitz SH, Behrends CN, Lowenstein M, et al. Lowering the Barriers to Medication Treatment for People with Opioid Use Disorder: Evidence for a Low-Threshold Approach. Penn LDI Cherish, January 18, 2022. Available at: Penn-LDI.CHERISH-Issue-Brief.January-2022.pdf (upenn.edu). Accessed February 24, 2025.

AHFS DI [database online]. Hudson, OH: Lexi-Comp, Inc.;http://online.lexi.com/lco/action/index/dataset/complete_ashp [available with subscription]. Accessed February 24, 2025.

American Hospital Formulary Service (AHFS). Drug Information 2025. methadone. [Lexicomp Online Web site]. 02/17/25. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed February 24, 2025.

American Hospital Formulary Service (AHFS). Drug Information 2025. naltrexone (c®). [Lexicomp Online Web site]. 02/17/25. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed February 24, 2025.

American Medical Association. Overdose Epidemic Report. Available at: https://end-overdose-epidemic.org/wp-content/uploads/2022/09/AMA-Advocacy-2022-Overdose-Epidemic-Report_090622.pdf. Accessed February 24, 2025.

American Society of Addiction Medicine (ASAM). Opioid Addiction 2016 Facts & Figures. Available at: http://www.asam.org/docs/default-source/advocacy/opioid-addiction-disease-facts-figures.pdf. Accessed February 24, 2025.

Center for Substance Abuse Treatment. Clinical Guidelines for the use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40. DHHS publication no. (SMA) 04-3939. Rockville, MD: Substance Abuse and Mental Health Services Administration (SAMHSA); 2004. Available at: https://www.ncbi.nlm.nih.gov/books/NBK64245/. Accessed February 24, 2025.

Cicero TJ, Ellis MS, Surratt HL, Kurtz SP. The changing face of heroin use in the United States: a retrospective analysis of the past 50 years. JAMA Psychiatry. 2014;71(7):821-826.

Department of Health and Human Services. Medications for the Treatment of Opioid Use Disorder. Office of the Secretary. 42 CFR Part 8. RIN 0930-AA39. 2024-01693.pdf (federalregister.gov). Accessed February 24, 2025.

DEA Methadone Fact Sheet. Drug Fact Sheet: Methadone (dea.gov). Accessed February 24, 2025.

Elsevier’s Clinical Pharmacology Compendium. buprenorphine. Indications/Dosages (Revised: 03/14/25). Mechanism of Action (Revised: 03/14/25). [Clinical Key Web site]. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed March 14, 2025.

Elsevier’s Clinical Pharmacology Compendium. naltrexone (Vivitrol®). 12/26/2024. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed February 24, 2025.

Garbutt JC, Kranzler HR, O'Malley SS, et al; Vivitrex Study Group. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial. JAMA. 2005 Apr 6;293(13):1617-1625.

Kampman K, Jarvis M. American Society of Addiction Medicine (ASAM) National practice guideline for the use of medications in the treatment of addiction involving opioid Use. 2015. Available at: http://www.asam.org/docs/default-source/practice-support/guidelines-and-consensus-docs/asam-national-practice-guideline-supplement.pdf?sfvrsn=24#search="naltrexone" or https://www.asam.org/resources/guidelines-and-consensus-documents/npg or https://www.asam.org/docs/default-source/practice-support/guidelines-and-consensus-docs/asam-national-practice-guideline-jam-article.pdf?sfvrsn=0. Accessed on February 24, 2025.

Krupitsky E, Nunes EV, Ling W, et al. Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial. Lancet. 2011;377(9776):1506-1513.

Lexi-Drugs Compendium. buprenorphine. 03/13/25. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 14, 2025.

Lexi-Drugs Compendium. naltrexone (Vivitrol®). 03/14/25. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 14, 2025.

Lexi-Drugs Compendium. methadone. 03/13/25. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 14, 2025.

Lobmaier P, Kornor H, Kunoe N, Bjørndal A. Sustained-Release Naltrexone For Opioid Dependence. Cochrane Database Syst Rev. 2008;(2) CD006140.

Dolophine Tablets [package insert]. Columbus, OH: Roxane Laboratories, Inc.; June 2021. Accessed February 24, 2025.

Methadone Injection [package insert]. Rockford, IL: Mylan Institutional LLC; 12/ 2023. Accessed February 24, 2025.

Methadone Oral Solution [package insert]. Columbus, OH: Roxane Laboratories, Inc.; 10/2024. Accessed February 24, 2025.

Methadone Intensol Concentrate [package insert]. Columbus, OH: Roxane Laboratories, Inc.; 01/ 2025. Accessed February 24, 2025.

Methadose Concentrate [package insert]. Hazelwood, MO: Mallinckrodt Inc.; 12/ 2023. Accessed February 24, 2025.

Methadose Tablets [package insert].Hazelwood, MO: Mallinckrodt Inc.; 09/ 2018. Accessed February 24, 2025.

Methadose Dispersible [package insert]. Hazelwood, MO: Mallinckrodt Inc.; 02/2020. Available at: Methadose™ Dispersible Tablets 40 mg | Mallinckrodt Pharmaceuticals. Accessed February 24, 2025.

National Academies of Sciences, Engineering, and Medicine. (2019). Medications for Opioid Use Disorder Save Lives. Washington, DC: The National Academies Press. Available at: https://doi.org/10.17226/25310. Accessed February 24, 2025.

Probuphine® (buprenorphine) implant. [prescribing information]. Titan Pharmaceuticals, Inc. South San Francisco, CA; 12/2023. Available at: https://probuphine.com/. Accessed February 24, 2025.

Probuphine® (buprenorphine) implant. [Probuphine® REMS Program]. Titan Pharmaceuticals, Inc. South San Francisco, CA. Available at: https://probuphinerems.com/. Accessed February 24, 2025.

Rudd RA, Seth P, David F, Scholl L. Increases in Drug and Opioid-Involved Overdose Deaths — United States, 2010–2015. MMWR Morb Mortal Wkly Rep. 2016;65:1445-1452.

Self-Compliance Tool for the Mental Health Parity and Addiction Equity Act (MHPAEA) (dol.gov). Available at: Self-Compliance Tool for the Mental Health Parity and Addiction Equity Act (MHPAEA) (dol.gov). Accessed February 24, 2025.

Sublocade (buprenorphine) extended-release subcutaneous injection. [prescribing information 02/2025]. Indivior Inc. North Chesterfield, VA. Available at: https://www.sublocade.com/. Accessed on February 24, 2025.

Sublocade (buprenorphine) extended-release subcutaneous injection. [Sublocade REMS Program]. Indivior Inc. North Chesterfield, VA. Available at: https://www.sublocaderems.com/. Accessed on February 24, 2025.

Substance Abuse and Mental Health Services Administration (SAMHSA). Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health; 2014. Available at: http://www.samhsa.gov/data/sites/default/files/NSDUH-FRR1-2014/NSDUH-FRR1-2014.pdf. Accessed on February 24, 2025.

Substance Abuse and Mental Health Services Administration (SAMHSA). Behavioral health trends in the United States: Results from the 2021 National Survey on Drug Use and Health; 2023. Available at: SAMHSA Announces National Survey on Drug Use and Health (NSDUH) Results Detailing Mental Illness and Substance Use Levels in 2021 | SAMHSA. Accessed on February 24, 2025.

Substance Abuse and Mental Health Services Administration (SAMHSA). Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Quick Guide for Physicians Based on TIP 40. 2005.

Substance Abuse and Mental Health Services Administration (SAMHSA). Programs & Campaigns » Medication-Assisted Treatment » Medication and Counseling Treatment » Naltrexone. Last Updated: 04/21/2022. Available at: https://www.samhsa.gov/medication-assisted-treatment/treatment/naltrexone. Accessed February 24, 2025.

Substance Abuse and Mental Health Services Administration (SAMHSA). Substance use disorders. 04/27/22. Available at: https://www.samhsa.gov/disorders/substance-use. Accessed February 24, 2025.

Substance Abuse and Mental Health Services Administration (SAMHSA).Medication-Assisted Treatment (MAT) | SAMHSA. Last Updated: 06/10/2022. Accessed February 24, 2025.

Truven Health Analytics. Micromedex® DrugDex® Compendium. buprenorphine. 03/13/25. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed March 14, 2025.

Truven Health Analytics. Micromedex® DrugDex® Compendium. naltrexone (Vivitrol®). 02/27/25. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed February 27, 2025.

Truven Health Analytics. Micromedex® DrugDex® Compendium. methadone. 03/13/25. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed March 14, 2025.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. buprenorphine (Probuphine®) prescribing information and approval letter (Original 12/15/2023; Updated 06/17/2022). [FDA Web site]. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed February 24, 2025.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. buprenorphine (Probuphine®) Approved Risk Evaluation and Mitigation Strategies (REMS). Initial 05/2016; Revised 11/01/2018. [FDA Web site]. Available at: http://www.accessdata.fda.gov/scripts/cder/rems/index.cfm?event=IndvRemsDetails.page&REMS=356. Accessed February 24, 2025.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. buprenorphine (Sublocade) prescribing information and approval letter (Original 11/30/2017; Updated 06/17/2022). [FDA Web site]. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed February 24, 2025.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. naltrexone (Vivitrol®) Approved Risk Evaluation and Mitigation Strategies (REMS). Initial 03/2010; Revised 09/22/2021. [FDA Web site]. Available at: https://www.accessdata.fda.gov/scripts/cder/rems/index.cfm?event=IndvRemsDetails.page&REMS=67. Accessed February 24, 2025.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. naltrexone (Vivitrol®) prescribing information and approval letter (Original: 04/13/06. Revised 09/30/2022). [FDA Web site]. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed February 24, 2025.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. methadone prescribing information and approval letter (Original 12/15/2004; Updated 12/15/2023). [FDA Web site]. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed February 24, 2025.

Vivitrol® (naltrexone) implant. [prescribing information]. Alkermes, Inc.; Waltham, MA. Original: 04/13/06. Revised 01/2024. Available at: https://www.vivitrol.com/opioid-alcohol-addiction-awareness?s_mcid=ppc-google-vivitrol-general-terms. Accessed February 24, 2025.

References for Naltrexone Implant

Kelty E, Hulse G. Fatal and non-fatal opioid overdose in opioid dependent patients treated with methadone, buprenorphine or implant naltrexone. Int J Drug Policy. 2017; 46:54-60.

Krupitsky E, Zvartau E, Blokhina E, et al. Randomized trial of long-acting sustained-release naltrexone implant vs oral naltrexone or placebo for preventing relapse to opioid dependence. Arch Gen Psychiatry. 2012 Sep;69(9):973-981.

Larney S, Gowing L, Mattick RP, Farrell M, Hall W, Degenhardt L. A systematic review and meta-analysis of naltrexone implants for the treatment of opioid dependence. Drug Alcohol Rev. 2014 ;33(2):115-128.

National Health and Medical Research Council (NHMRC). Naltrexone implant treatment for opioid dependence. 2015. Available at: https://www.nhmrc.gov.au/about-us/publications/naltrexone-implant-treatment-opioid-dependence#block-views-block-file-attachments-content-block-1. Accessed February 24, 2025.

Soyka M, Kranzler HR, van den Brink W, et al.; WFSBP Task Force on Treatment, Guidelines for Substance Use Disorders. The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of substance use and related disorders. Part 2: Opioid dependence. World J Biol Psychiatry. 2011;12(3):160-187.

US Food and Drug Administration (FDA). FDA Compounding Laws and Policies. 09/10/2020. Available at: https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm606881.htm. Accessed February 24, 2025.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

See Attachment A.

HCPCS Level II Code Number(s)

MEDICALLY NECESSARY

G2086 Office-based treatment for opioid use disorder, including development of the treatment plan, care coordination, individual therapy and group therapy and counseling; at least 70 minutes in the first calendar month

G2087 Office-based treatment for opioid use disorder, including care coordination, individual therapy and group therapy and counseling; at least 60 minutes in a subsequent calendar month

G2088 Office-based treatment for opioid use disorder, including care coordination, individual therapy and group therapy and counseling; each additional 30 minutes beyond the first 120 minutes (list separately in addition to code for primary procedure)

J2315 Injection, naltrexone, depot form, 1 mg

Q9991 Injection, buprenorphine extended-release (sublocade), less than or equal to 100 mg

Q9992 Injection, buprenorphine extended-release (sublocade), greater than 100 mg

EXPERIMENTAL/INVESTIGATIONAL

THE FOLLOWING CODE IS USED TO REPRESENT NALTREXONE IMPLANTS:

J7999 Compounded drug, not otherwise classified

Revenue Code Number(s)

USE THE FOLLOWING CODE FOR METHADONE MAINTENANCE THERAPY:

0944 Other Therapeutic Services (see also 095X, an extension of 094X)-Drug Rehabilitation

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From 08.01.37f:

10/02/2024

This version of the policy will be issued on 08/11/2025 with a retroactively effective date of 10/02/2024.

This policy has been updated to reflect final rule recommendations. This final rule modifies and updates certain provisions of regulations related to Opioid Treatment Program (OTP) accreditation, certification, and standards for the treatment of Opioid Use Disorder (OUD) with Medications for Opioid Use Disorder (MOUD) in OTPs. This includes making flexibilities put forth during the COVID-19 Public Health Emergency (PHE) permanent, as well as expanding access to care and evidence-based treatment for OUD. The effective date of this final rule is April 2, 2024, and the compliance date is October 2, 2024.

Buprenorphine (Probuphine) implants was removed from the market 10/2020 and no longer available in US, thus was removed from the policy.

Revisions From 08.01.37e:

01/01/2025	This policy has been identified for the HCPCS code update, effective 01/01/2025. Inclusion of a policy in a Code Update memo does not imply that a full review of the policy was completed at this time. The following HCPCS codes have been removed from this policy: J0570 Buprenorphine implant, 74.2 mg

Revisions From 08.01.37d:

10/02/2024

This version of the policy will be issued on 10/21/2024 with a retroactively effective date of 10/02/2024.

Revisions From 08.01.37c:

05/29/2024	This policy has been reissued in accordance with the Company's annual review process.
04/10/2023	This version of the policy will become effective 04/10/2023. This policy has been updated to include the Company's coverage position on buprenorphine injection. The following provider requirement was removed from medically necessary criteria: Prescribers must obtain a waiver as per the requirements in the Drug Addiction Treatment Act (DATA) of 2000.

05/29/2024

This policy has been reissued in accordance with the Company's annual review process.

04/10/2023

This version of the policy will become effective 04/10/2023.

This policy has been updated to include the Company's coverage position on buprenorphine injection.

The following provider requirement was removed from medically necessary criteria:

Prescribers must obtain a waiver as per the requirements in the Drug Addiction Treatment Act (DATA) of 2000.

Revisions From 08.01.37b:

01/01/2023

This version of the policy will become effective 01/01/2023.

This policy has been updated to include the Company's coverage position on methadone maintenance therapy as Medically Necessary with criteria.

Revisions From 08.01.37a:

08/11/2021	This policy has been reissued in accordance with the Company's annual review process.
11/04/2019	This policy has been updated to include the Company’s coverage position on buprenorphine (Sublocade^TM) extended-release subcutaneous injection (as Medically Necessary) and naltrexone implants (as Experimental/Investigational). Policy criteria has been modified for naltrexone (Vivitrol®).

Effective 10/05/2017 this policy has been updated to the new policy template format.

Version Effective Date:

10/2/2024

Version Issued Date:

7/28/2025

Version Reissued Date: