Last Review Date: 06/01/2023

Date of Origin: 10/01/2018

Dates Reviewed: 10/2018, 06/2023

1. Description of Procedure or Service

Implantable buprenorphine (Probuphine®) is indicated for the maintenance treatment of opioid dependence in patients who have achieved and sustained prolonged clinical stability on low-to-moderate doses of a transmucosal buprenorphine-containing product (i.e., doses of no more than 8 mg per day of Subutex or Suboxone sublingual tablet equivalent or generic equivalent). It is intended to be used as part of a complete treatment program to include counseling and psychosocial support.

Under the Drug Addiction Treatment Act (DATA) codified at 21 United States Code (U.S.C.) 823(g), use of this product in the treatment of opioid dependence is limited to physicians who meet certain qualifying requirements, and who have notified the Secretary of Health and Human Services

(HHS) of their intent to prescribe or dispense this product for the treatment of opioid dependence and have been assigned a unique identification number that must be included on every prescription.

Each dose consists of four Probuphine implants inserted subdermally in the inner side of the upper arm. Probuphine subdermal implants are intended to be in place for 6 months of treatment and removed by the end of the sixth month.

After one insertion in each arm (12 months), most patients should be transitioned back to a transmucosal buprenorphine-containing product for continued treatment. There is no experience with inserting additional implants into other sites in the arm to recommend a second insertion into a previously-used arm. Neither re-insertion into previously-used administration sites, nor into sites other than the upper arm, has been studied.

2. Policy

The use of buprenorphine implants is considered not medically necessary.

Note: Buprenorphine implants are likely to produce outcomes equivalent to sublingual buprenorphine, but are considerably more costly. As there are equally effective services covered under the prescription benefit (see Buprenorphine and Buprenorphine/Naloxone for Opioid Dependence) as well as the medical benefit (see Methadone Treatment for Opiate Addiction). In addition to the lack of pharmacy system regulations, safety concerns

3. Key Points

Coverage is allowed for opioid dependence treatment as a part of a medication assisted treatment program with criteria outlined in the Buprenorphine and Buprenorphine/Naloxone for Opioid Dependence Prior Authorization Policy and the Methadone Treatment for Opiate Addiction Medical Policy. Both policies utilize medication as part of a comprehensive substance use disorder treatment program that includes counseling and psychosocial support. The rationale to not include Probuphine as a coverage option is due to significant limitations of use and safety concerns that are not seen with the covered programs as outlined below. Additionally, Probuphine is considerably more costly than either of the covered programs without significant added benefit.

Due to the duration of therapy with the implantable dosage form of buprenorphine, patients will no longer be required to see their prescriber monthly to obtain new prescriptions for buprenorphine. There is an increased risk that members may not receive the routine (e.g., monthly) monitoring, assessment, and concomitant psychosocial therapies that are intended and recommended in conjunction with medication therapy. This poses a risk to the patient being successful in recovery from substance abuse. Probuphine patients may be more likely to rely solely on medication for treatment of substance abuse (without the necessary psychosocial support and therapy typically recommended) when the accountability with their prescriber is lessened. All data supporting the efficacy of buprenorphine products in the treatment of substance abuse is when buprenorphine is part of a more comprehensive treatment plan (i.e., medication assisted therapy).

Additionally, subdermal implantation of buprenorphine poses safety concerns related to the insertion and potential for expulsion of the implants. Prescribers of buprenorphine and buprenorphine/naloxone may lack the surgical skills or sterile office requirements for implantation of Probuphine. While prescribers are required to complete a REMS certification program, there are risks of improperly placed implants creating additional medical complications such as infection. The risk of expulsion of the implanted product has also been addressed in the product’s labeling. There is a Black Box Warning stating that insertion and removal of Probuphine are associated with the risk of implant migration, protrusion, expulsion, and nerve damage resulting from the procedure.

Furthermore, there are risks when a drug with an extended duration of action, such as an implantable dosage form like Probuphine, is implanted if other drugs of abuse are consumed. If the steady low dose of buprenorphine implanted is no longer sufficient to satisfy cravings, the patient may seek additional opioids to combat withdrawal symptoms further adding to drug levels already in the body. The risk of respiratory and central nervous system depression associated with concomitant use of benzodiazepines is still present with Probuphine and could prove dangerous in a patient with implanted buprenorphine.

In addition, there are operational constraints that pose a risk to patient safety. Drug utilization review (DUR) edits exist in the pharmacy claims system for various reasons. Most importantly, they alert the pharmacists of drug interactions or contraindications with drugs on the patient’s profile. In opioid dependent patients, the DUR edits alert the pharmacist of life-threatening drug interactions prior to the dispensing of the medication. It also serves as a method to track compliance as it alerts when concomitant opioids are prescribed. By implanting buprenorphine in the physician’s office, the claim for the medication does not process under the prescription benefit so the inherent safety measures incorporated cannot be realized.

Lastly, limitations to the use of Probuphine also exist in the requirement that only patients who are stable on 8mg or less of sublingual buprenorphine daily may benefit. The majority of buprenorphine users require more than 8mg per day or require supplemental dosing to control withdrawal symptoms, making the implantable buprenorphine inappropriate for use. As options for opioid dependence treatment exist with methadone and buprenorphine transmucosal products when coverage criteria are met, the risks of treatment with Probuphine do not support medical necessity.

4. Billing Code/Availability Information

HCPCS:

• J0570 – Buprenorphine implant, 74.2 mg: 1 billable unit = 74.2 mg

NDC:

• Probuphine implant kit consisting of four individually packaged sterile implants of 74.2 mg each and one individually packaged sterile disposable applicator: 52440-0100-xx

5. References

1. Probuphine [package insert]. Princeton, NJ; Braeburn; June 2022. Accessed May 2023.
2. Psychopharmacology Drugs Advisory Committee to the FDA meeting materials. January 12, 2016. Available at: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/ucm475314.htm. Accessed October 23, 2018.
3. Opioid Overdose. Centers for Disease Control and Prevention. Available at: http://www.cdc.gov/drugoverdose/index.html. Accessed October 23, 2018.
4. Psychopharmacology Drugs Advisory Committee to the FDA meeting materials. January 12, 2016. Available at: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/ucm475314.htm. Accessed October 23, 2018.
5. Kleber HD, Weiss RD, Anton RF, et al. Practice guideline for the treatment of patients with substance abuse disorders. 2006; American Psychiatric Association; 1-275. Available at: http://psychiatryonline.org/guidelines.aspx. Accessed October 23, 2018.
6. Drugs@FDA. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed October 23, 2018. 
7. The American Society of Addiction Medicine (ASM). National Practice Guideline for the Use of Medications in Treatment of Addiction Involving Opioid Use. December 2019. Available at: https://www.asam.org/docs/default-source/quality-science/npg-jam-supplement.pdf?sfvrsn=a00a52c2_2.
8. Reus VI, Fochtmann LJ, Bukstein O, et al. The American Psychiatric Association Practice Guideline for the Pharmacological Treatment of Patients With Alcohol Use Disorder. Am J Psychiatry. 2018 Jan 1;175(1):86-90.
9. The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update. J Addict Med. 2020 Mar/Apr;14(2S Suppl 1):1-91. doi: 10.1097/ADM.0000000000000633.
10. Nasser AF, Greenwald MK, Vince B, et al. Sustained-Release Buprenorphine (RBP-6000) Blocks the Effects of Opioid Challenge With Hydromorphone in Subjects With Opioid Use Disorder. J Clin Psychopharmacol. 2016 Feb;36(1):18-26. doi: 10.1097/JCP.0000000000000434. PMID: 26650971; PMCID: PMC5549150.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD) and Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. They can be found at: http://www.cms.gov/medicare-coverage-database/search/advanced-search.aspx. Additional indications may be covered at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD): N/A