By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved the first once-monthly injectable buprenorphine, a partial opioid agonist, for the treatment of moderate-to-severe opioid use disorder. Buprenorphine is formulated in a biodegradable polymer and biocompatible solvent (Atrigel) designed to deliver the drug at a controlled rate over a one-month period after subcutaneous administration. The FDA assigned this product a priority review and a fast-track designation. It is marketed as Sublocade.
Buprenorphine extended-release injection is indicated for the treatment of moderate-to-severe opioid use disorder in patients who have initiated treatment with a transmucosal buprenorphine-containing product, followed by dose adjustment for a minimum of seven days.1 The manufacturers recommend using the product as part of a complete treatment program that includes counseling and psychosocial support.
The recommended dose is two monthly subcutaneous injections of 300 mg, followed by 100 mg monthly maintenance doses.1 The maintenance dose may be increased to 300 mg monthly if benefits outweigh risks.
The product should be prepared and administered by a healthcare provider. Buprenorphine extended-release injection is available as prefilled syringes of 100 mg/0.5 mL and 300 mg/1.5 mL.
Buprenorphine extended-release injection provides another treatment option that reduces the burden of daily medications. It can be used for patients on up to 24 mg/day of transmucosal buprenorphine. The previously approved buprenorphine implant is only for patients on transmucosal buprenorphine doses < 8 mg/day.2
Serious harm or death could result if buprenorphine extended-release injection is administered intravenously as a solid mass develops on contact with body fluids, which may cause occlusion, local tissue damage, or thromboembolic events, including life-threatening pulmonary emboli.1 Other side effects (5-8.5%) include constipation, nausea, vomiting, headache, drowsiness, injection site pain/itching, and elevation of liver enzymes.1
Buprenorphine extended-release injection was evaluated in an opioid blockade study and a randomized, double-blind, placebo-controlled, 24-week, efficacy and safety study in subjects with moderate-to-severe opioid use disorder.1 In the blockade study, 39 subjects who were stabilized with 8-24 mg/day of sublingual buprenorphine, were challenged with placebo (weeks 1-4), followed by intramuscular 6 mg and 18 mg of hydromorphone (weeks 5-12) after an injection of buprenorphine extended-release injection at the start of weeks 1 and 5. The peak effect of “drug-liking” behavior was assessed based on a 100-point visual analog scale using a noninferiority margin of < 20 (i.e., hydromorphone not substantially more likeable than placebo by this margin). Results indicated noninferiority in “drug liking” between buprenorphine extended-release injection and placebo. Complete blockage was observed throughout the eight weeks of observation after the second injection. In the efficacy trial, subjects (n = 504) were randomized to six monthly 300 mg injections, two once-monthly 300 mg doses, followed by four once-monthly injections of 100 mg for buprenorphine extended-release, or six once-monthly placebo injections. All subjects were controlled on sublingual buprenorphine/naloxone and received manual-guided, individual psychosocial support at least once a week. Efficacy was assessed over weeks 5-24 based on weekly urine drug screens and self-reported use of illicit opioid use. A “grace period” for weeks 1-4 was allowed for stabilization in treatment. Missing data were counted as positive use. Over 20 weeks, the proportions achieving success (≥ 80% opioid-free weeks) were 28.4%, 29.1%, and 2% for placebo, respectively.
More than 2.5 million Americans suffer from opioid use disorder.3 Currently recognized effective medication treatments include buprenorphine, methadone, and extended-release naltrexone. Buprenorphine extended-release injection provides another option to sublingual tablets and subcutaneous implants for opioid dependence. It is only available through a restricted program called the SUBLOCADE REMS program.1 Healthcare settings and pharmacies that order and dispense the product must be certified and comply with the REMS requirements. Cost was not available at the time of this review.