(106) The Promise of Extended-Release Buprenorphine for Opioid Use Disorder

Background & Introduction: Opioid use disorder (OUD) accounts for 20-41% of U.S. pregnancy-associated deaths, with highest overdose risk at 7-11 months postpartum. Medications for OUD (MOUD) during pregnancy increase prenatal care and reduce morbidity and mortality. However, less than 30% of perinatal individuals with OUD receive MOUD. Buprenorphine is safe and effective in pregnancy and comes in sublingual (SL) formulations and, more recently, two extended-release (ER) formulations.

ER-buprenorphine shows promise in overcoming barriers to SL formulations. However, ER-buprenorphine trials excluded perinatal patients, and ER formulations contain N-Methyl-2-pyrrolidone (NMP), which poses theoretical fetal risk. Perinatal ER-buprenorphine literature is limited to four case reports in pregnancy and two postpartum case series. Results were mixed, but ER-buprenorphine discontinuation due to side effects was common. However, no published perinatal studies focus on patients using fentanyl or taking typical therapeutic SL-buprenorphine doses in the fentanyl era. Our aim was to describe outcomes for ER-buprenorphine among a cohort of peripartum individuals with OUD and high fentanyl exposure.

Case Description: We conducted a retrospective case series of patients treated with ER-buprenorphine during pregnancy to one year postpartum from 1/1/2023-5/1/2025 in an urban, academic, peripartum substance use disorder clinic. This study was deemed Penn IRB exempt. We extracted data from the electronic medical record and reviewed urine drug tests (UDT) collected at each perinatal outpatient appointment per clinic protocol. The presence of buprenorphine, and its metabolite norbuprenorphine, assessed buprenorphine adherence. All charts were double coded, and we used descriptive statistics to characterize the sample and describe clinical outcomes.

15 patients received ER-buprenorphine during pregnancy or postpartum out of 96 total patients. Mean age was 34.5 years, and the majority identified as White and were Medicaid insured. Thirteen patients used fentanyl and two misused prescription opioids. Polysubstance use was common, as were mental health and medical comorbidities.

All patients initially took SL-buprenorphine before switching to ER-buprenorphine. Fourteen patients received RBP-6000 (Sublocade), and one received CAM2038 (Brixadi), which became available later in the study period. Five patients received ER-buprenorphine during pregnancy. A final pregnant patient received her last RBP-6000 dose at five weeks, with buprenorphine and norbuprenorphine levels detected throughout pregnancy despite no additional buprenorphine. Nine patients initiated ER-buprenorphine postpartum, with the average initiation at 5.13 months after delivery.
The predominant reason for switching to ER-buprenorphine was nausea with SL-buprenorphine in pregnant patients and dosing convenience in the postpartum group. Additional reasons included stigma, medication loss/theft, and persistent cravings/use on maximum SL-buprenorphine.

Side effects were minimal and included euphoria in one patient and nausea and vomiting in another patient after receiving the loading dose. Two patients needed supplemental SL-buprenorphine daily during week four after injection to manage cravings.

In both prenatal and postpartum groups, receipt of ER-buprenorphine was associated with increased UDT norbuprenorphine positivity and decreased substance use. Both groups also showed total cessation of non-prescribed opioids (46% to 0% positive in prenatal, 18% to 0% postpartum) and reduction in other substances (31% to 1% positive in prenatal, 13% to 2% postpartum). Three patients opted to stop ER-buprenorphine postpartum due to perceived stability; two had no return to use after ER-buprenorphine cessation while the third suffered a non-fatal overdose 12 months postpartum. There were no significant maternal, fetal, or neonatal adverse effects among the pregnant group, including no cases of neonatal abstinence syndrome.

Conclusion & Discussion: This retrospective case series of perinatal ER-buprenorphine demonstrates preliminary favorable safety and treatment outcomes for people at high risk of OUD-related maternal and fetal complications. All patients exhibited increased buprenorphine adherence, total opioid cessation, and decreased non-opioid substance use after starting ER-buprenorphine.

Adverse effects and pregnancy complications were minimal. No infants experienced side effects from NMP, though notably, all patients initiated after organogenesis. Three patients voluntarily discontinued ER buprenorphine within the first postpartum year due to perceived stability, with one experiencing a nonfatal overdose. Given the elevated overdose risk postpartum,2 it is crucial to discuss the importance buprenorphine continuation for at least a full year postpartum.

Limitations of this study include its single-site, small size, lack of control group, and potential selection bias for ER-buprenorphine recipients. This study was conducted in a Philadelphia, which has a potent fentanyl drug supply with adulterants so may not generalize.

This is the largest U.S. study to date reporting outcomes for pregnant and post-partum patients treated with ER-buprenorphine and provides support for use in perinatal patients where standard treatment options are inadequate.

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