Extended-Release Buprenorphine Viable, Safe During Pregnancy

Extended-release buprenorphine was an effective treatment for pregnant women with opioid use disorder (OUD) and safe for their babies, according to an open-label randomized trial.

Women randomized to weekly, injectable extended-release buprenorphine had higher rates of abstinence from illicit opioids than those in the sublingual buprenorphine group (82.5% vs 72.6%, P=0.009), reported T. John Winhusen, PhD, of the University of Cincinnati, and colleagues.

Those taking extended-release buprenorphine also had fewer serious adverse events during pregnancy (8.7% vs 26.8%, P=0.007) and during the postpartum period (6% vs 18.6%, P=0.04). While rates of nonserious AEs did not differ between groups, more were considered related to extended-release buprenorphine during pregnancy (26.1% vs 7%, P=0.003), although they “were mostly mild,” the researchers wrote in JAMA Internal Medicine.

Postpartum abstinence rates were similar in both groups (60.2% for extended-release and 59.5% for sublingual), they noted.

“These findings support weekly extended-release buprenorphine as another viable treatment option for pregnant and postpartum patients with opioid use disorder,” Winhusen told MedPage Today, adding that in other areas of medicine, the value of having multiple therapeutic options is recognized, and the same should ring true for OUD.

Winhusen also said his team “did not see worse neonatal opioid withdrawal outcomes among infants exposed to extended-release buprenorphine, despite the higher overall buprenorphine exposure with the injectable formulation.”

Overall, 30.2% of the extended-release group and 26.5% of the sublingual group required treatment for neonatal opioid withdrawal syndrome; nor were there any significant differences in neonatal opioid treatment time (10.9 vs 14.8 days, respectively).

Winhusen and colleagues did find that, at birth, neonates in the extended-release group actually had larger mean head circumference than the sublingual group (34.0 vs 33.4 cm; P=0.049). However, they noted that “both groups’ averages [for head circumference] were within normal range. This finding’s clinical significance is unclear, but it is reassuring given the higher exposure from extended-release buprenorphine.”

Sublingual buprenorphine requires daily dosing and medication levels vary throughout the day. Extended-release buprenorphine sidesteps some of these challenges, though research on its safety for moms and babies in pregnancy is lacking.

In an accompanying invited commentary, Mishka Terplan, MD, MPH, of the Friends Research Institute in Baltimore, and colleagues, called the trial “valuable — overdue.” The findings “provide clear support for including weekly extended-release buprenorphine alongside sublingual buprenorphine and methadone within the standard of care for perinatal patients,” they wrote.

Terplan’s group noted that pregnant patients are often excluded from clinical trials, creating gaps in knowledge and care. This practice “is grounded in the misconception that fetal protection demands avoidance of research,” they wrote, and argued that it is a “fallacy that ultimately impedes evidence needed to guide treatment decisions in pregnancy.”

The intent-to-treat, two-group, non-inferiority randomized clinical trial took place at 13 U.S. sites between July 2, 2020 and October 30, 2024.

A total of 140 participants between 6 and 30 weeks’ gestation were randomized to receive either standard sublingual buprenorphine (target dose 16 mg/d) or weekly injectable extended-release buprenorphine (24 mg), though dosing was determined by the clinician. Prior to randomization, all but two participants were already prescribed sublingual buprenorphine.

Participants were followed weekly throughout pregnancy up to 12 months postpartum. Most completed treatment through pregnancy (98%) and 81% did through 12 months postpartum. The primary outcome was illicit opioid abstinence during pregnancy, measured using weekly urine drug screens.

Women with physiological dependence on alcohol or sedatives requiring medically managed withdrawal were excluded, as were those with certain psychiatric and medical conditions and criminal justice cases that may interfere with study participation. Those receiving methadone or naltrexone treatment were also excluded.

Most participants were white (82.9%) while 7.1% were Black, 7.1% were Hispanic, and 10% belonged to other groups; mean maternal age was 31.2.

The authors noted that future work is needed in more diverse racial and ethnic groups. Study limitations were the more clinically stable patient population compared with many other pregnant people with OUD, and the fact that outcomes based on medical records may have been hampered by “missing data and potential quality issues,” they stated.

Winhusen said that more research is also needed to “better understand which patients may benefit most from this treatment approach and how extended-release formulations can best be integrated into perinatal addiction care.”