Weekly Extended-release Buprenorphine Effective During Pregnancy

Sublingual buprenorphine (SUB) is a standard treatment for opioid use disorder (OUD) during pregnancy, but less is known about the efficacy and safety of extended-release (XRB) formulations in this setting. Researchers conducted an open-label, non-inferiority randomized trial to evaluate the efficacy and safety of XRB in comparison with SUB in pregnant persons with OUD. Patients randomized to XRB received weekly Brixadi injections during pregnancy and breastfeeding periods because of concerns about exposure to an agent in the monthly formulations (N-methyl-2-pyrrolidone).

• There were 140 participants; 69 were randomized to XRB and 71 to SUB. Pregnancy and postpartum phases were completed by 98 percent and 81 percent of patients, respectively, with no between-group differences.
• Participants receiving XRB had significantly more weekly drug tests negative for other opioids during pregnancy (83 percent versus 73 percent), but not during the postpartum phase (60 percent in both groups), compared with those receiving SUB.
• Head circumference at birth was significantly larger among neonates in the XRB group, compared with those in the SUB group (34cm versus 33.4cm).
• There were no significant differences between groups in the frequency or duration of neonatal abstinence syndrome, or for other fetal outcome measures.

Comments: These findings support the administration of weekly extended-release buprenorphine for OUD in pregnancy. Although the study did not raise any safety concerns, it was powered for efficacy, not safety, and further surveillance will be needed to assess this, including the safety of the monthly formulations. The logistics of providing weekly injections present a barrier to implementation that also needs to be addressed.

Darius A. Rastegar, MD

Reference: Winhusen TJ, Lofwall MR, Kropp F, et al. Extended-release vs sublingual buprenorphine in pregnancy through 12 months post partum: a randomized clinical trial. JAMA Intern Med. 2026;186(5):533–543.