Extended-Release Subcutaneous Buprenorphine Injection May Reduce Fentanyl Use


HCPLive spoke with Joshua M. Cohen, MD, MPH, to discuss a post-hoc analysis of a phase 3 study that showed buprenorphine may be effective at reducing fentanyl use.

Extended-Release Subcutaneous Buprenorphine Injection May Reduce Fentanyl Use

Joshua Cohen, MD, MPH

Credit: Braeburn

A post hoc analysis suggests buprenorphine (Brixadi) may be effective for treating opioid use disorder (OUD) with fentanyl use and extended-release subcutaneous injected formulation may help in reducing fentanyl use.1

“We did see that Brixadi was found to be non-inferior to sublingual buprenorphine in the primary endpoint of responder rate for negative opioid assessments but was also found to be superior to sublingual buprenorphine in the cumulative distribution function that measured the overall percentage of negative urine over the course of the study,” Joshua M. Cohen, MD, MPH, FAHS, chief medical officer at Braeburn told HCPLive.

On May 23, 2023, the FDA approved buprenorphine as an extended-release subcutaneous injection for the treatment of moderate to severe OUD.2 This marked the first long-acting buprenorphine injectable with both weekly and monthly doses. A boxed warning indicates it should only be used by healthcare professionals since it could be dangerous if accidentally injected into a vein instead of the subcutaneous space.

Yet, limited data exists on the effectiveness of OUD medications, like buprenorphine, among patients using fentanyl, a potent opioid. Investigators, led by Edward V. Nunes, MD, from the Columbia University Irving Medical Center Department of Psychiatry, sought to evaluate the effectiveness of sublingual or extended-release injection formulations of subcutaneous buprenorphine for OUD treatment among patients with and without fentanyl use.1

The team conducted a post hoc analysis of a 24-week, randomized, double-blind clinical trial conducted at 35 outpatient sites in the US from December 2015 to November 2016 comparing patients on sublingual buprenorphine-naloxone vs extended-release subcutaneous injection buprenorphine. Participants were placed into the following groups: presence of fentanyl vs absence of fentanyl or norfentanyl in urine at baseline. They had urine testing weekly for 12 weeks, followed by 6 urine testings between weeks 13 and 24. Investigators analyzed the data on an intention-to-treat basis from March 2022 to August 2023.

The main outcomes were retention in treatment, percentage of urine samples negative for any opioids, percentage of urine samples negative for fentanyl or nor-fentanyl, and scores withdrawal scales and visual analog craving scales.

The study included 428 participants and 123 did not have baseline fentanyl use. In the fentanyl-positive group, the mean percentage of urine samples negative for fentanyl during the study was 74.6% among participants receiving subcutaneous buprenorphine and 61.9% among participants receiving sublingual buprenorphine-naloxone (difference, 12.7%; 95% confidence interval [CI], 9.6% - 15.9%. Investigators noted the treatment rapidly reduced opioid withdrawal and craving scores in all groups.

Investigators saw buprenorphine appeared to be effective for patients with baseline fentanyl use, although fentanyl use had fewer opioid-negative urine samples during the study than the fentanyl-negative subgroup. The data was consistent with a lot of data on fentanyl. Cohen said fentanyl use represented a more difficult-to-treat group of patients, more significant disease, and greater overall opioid exposure since fentanyl is more potent than heroin.

“We believe that most of the patients who did test fentanyl positive in this study believed that they were using heroin but were probably being exposed to fentanyl because that was around the time that we started to see the increase of fentanyl presence in the drug supply,” Cohen said.

Ultimately, the trial included 3 overdoses, and all of them were patients treated with sublingual buprenorphine (1 in the fentanyl-negative group and 2 In the fentanyl-positive group)—none treated with subcutaneous buprenorphine. Many patients did not realize they were exposed to fentanyl which is 30 – 50 times more potent than heroin and has worsened the opioid overdose epidemic.

“Because of that, I think that there [was] concern that maybe buprenorphine wouldn't work as well in people with fentanyl, but these results are consistent with a number of recent observational studies that also suggest that buprenorphine is effective in the presence of fentanyl,” Cohen said. “That information [and] that consistency with those other studies is also useful for clinicians.”


  1. Nunes EV, Comer SD, Lofwall MR, et al. Extended-Release Injection vs Sublingual Buprenorphine for Opioid Use Disorder With Fentanyl Use: A Post Hoc Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024;7(6):e2417377. Published 2024 Jun 3. doi:10.1001/jamanetworkopen.2024.17377
  2. Braeburn's BRIXADI™ (buprenorphine) Extended-Release Subcutaneous Injection (CIII) Receives FDA Approval for Moderate to Severe Opioid Use Disorder. https://www.prnewswire.com/news-releases/braeburns-brixadi-buprenorphine-extended-release-subcutaneous-injection-ciii-receives-fda-approval-for-moderate-to-severe-opioid-use-disorder-301832521.html#:~:text=PLYMOUTH%20MEETING%2C%20Pa.%2C%20May,OUD)%20in%20patients%20who%20have. Accessed July 2, 2024.

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