By William Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Medical Director, Pharmacy, Northern California Kaiser Permanente, and Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA.

Drs. Elliott and Chan report no financial relationships relevant to this field of study.

The FDA has approved the first buprenorphine implant for the treatment of opioid dependence. Buprenorphine is a partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor. Buprenorphine was previously approved as oral and sublingual tablets. The implant is marketed as Probuphine.


Buprenorphine implant 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 (< 8 mg/day).1


A trained professional inserts the buprenorphine implant subdermally in a patient’s upper arm, leaving the implant there for six months before removal.1 It should be used as part of a complete treatment program that includes counseling and psychosocial support. Each ethylene vinyl acetate implant (2.5 mm diameter x 26 mm length) contains 80 mg of buprenorphine HCl (74.2 mg of buprenorphine base).


The implant provides a more convenient form of delivery with sustained medication for six months. This form of buprenorphine offers convenience and eliminates the risk of the patient forgetting to take the medication or someone stealing it, factors the FDA considered advantageous during the approval process.


The implant contains 80 mg of a drug that could be expelled or removed, resulting in accidental exposure or misuse.1 Insertion and removal of the implants are associated with the risk of migration, protrusion, expulsion, and nerve damage from the procedure.1 Most frequent adverse events were implant-site pain, pruritus, and erythema.1


The efficacy of the buprenorphine implant was demonstrated in one randomized, double-blind, double-dummy, six-month study in 178 subjects.1 Study subjects met the DSM-IV-TR criteria for opioid dependency as a primary diagnosis and were clinically stable on sublingual buprenorphine at a dose of no more than 8 mg/day.1

Healthcare providers attested to the clinical stability based on a checklist that included no reports of illicit opioid use, no withdrawal symptoms, no hospital admissions or ED visits in the past 90 days, low to no desire to use illicit opioids, stable living and work environments, and compliance with clinical/behavior/cognitive visits.

Subjects were randomized to buprenorphine implants and placebo sublingual tablets or sublingual buprenorphine/naloxone and placebo implants. Supplemental dosing with sublingual buprenorphine/naloxone was allowed if clinically appropriate. Efficacy was based on four randomly scheduled urine toxicology screens and patients self-reporting to detect opioid use over the six-month period. Subjects in the buprenorphine arm who required supplemental buprenorphine were considered as non-responders.

The proportion of subjects with no evidence of illicit drug use was 63% for the implant and 64% for usual sublingual buprenorphine/naloxone. The implant appears to be less effective if the daily buprenorphine dose is > 8 mg. In two studies in subjects stabilized on 12-16 mg/day, the success rate for the implant was about 30% at weeks 17 to 24, which was similar to sublingual buprenorphine, in one study and 37% for the full 24 weeks in the second study.2,3


Buprenorphine (with or without naltrexone) and methadone are approved and effective drugs for management of opioid dependence.4,5 Buprenorphine, in contrast to methadone, can be prescribed in an office-based setting as opposed to a federally authorized opioid treatment clinic.6,7 The implant provides another option for those who have been stabilized on low-to-moderate doses of sublingual buprenorphine.

The implant is only available to certified healthcare providers through the PROBUPHINE REMS Program. Prescribers and providers who plan to insert or remove the implants must successfully complete a live training program. Cost was not available at the time of this review.


  1. Probuphine Prescribing Information. Titan Pharmaceuticals Inc. May 2016.
  2. Rosenthal RN, Ling W, Casadonte P, et al. Buprenorphine implants for treatment of opioid dependence: Randomized comparison to placebo and sublingual buprenorphine/naloxone. Addiction 2013;108:2141-2149.
  3. Ling W, Casadonte P, Bigelow G, et al. Buprenorphine implants for treatment of opioid dependence: A randomized controlled trial. JAMA 2010;304:1576-1583.
  4. Mattick RP, Breen C, Kimber J, et al. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev 2014; doi: 10.1002/14651858.CD002207.pub4.
  5. Substance Abuse and Mental Health Services Administration. Federal Guidelines for Opioid Treatment Programs. Available at: Accessed June 4, 2016.
  6. Ling W. Buprenorphine implant for opioid addiction. Pain Manag 2012;2:345-350.
  7. U.S. Department of Health and Human Services. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction: A Treatment Improvement Protocol. Available at: Accessed June 4, 2016.