(129) Rapid Outpatient Initiation of Long-Acting Injectable Buprenorphine: A Case Series

Background & Introduction: Buprenorphine is a lifesaving medication for opioid use disorder in the setting of an overdose epidemic driven by fentanyl, which has in recent years claimed over 100,000 lives annually.1 However, initiating buprenorphine in real-world ambulatory settings is challenging in the fentanyl era. Because fentanyl is long-acting, patients who regularly use fentanyl typically must withdraw for 24 hours or more before initiating sublingual buprenorphine or risk precipitating withdrawal. Innovative buprenorphine initiation strategies are needed to overcome challenges to initiating this highly effective treatment.2 Clinical trials demonstrate that long-acting injectable buprenorphine (LAIB) is at least as effective as sublingual buprenorphine (SL-BUP) 3. LAIB has been administered to patients with minimal to mild withdrawal symptoms who are initiating buprenorphine in emergency departments without first receiving SL-BUP (rapid initiation of LAIB or rALIB), providing a new option for buprenorphine initiation in the fentanyl era .4 However, there have been no studies of rLAIB in the outpatient setting where there is commonly less access to supportive medications and capacity for patient monitoring, but where the majority of buprenorphine initiations happen. In this report, we describe a case series of 13 patients who received rLAIB in outpatient settings to illustrate rLAIB feasibility and clinical outcomes.

Case Description: The rLAIB outpatient protocol was designed to initiate LAIB for patients with mild to no opioid withdrawal and no recent sublingual buprenorphine. After a discussion of what to expect and rLAIB risks and benefits, patients are administered a weekly dose of LAIB (Brixadi 8mg, 16mg, 24mg or 32mg). Weekly Brixadi reaches peak plasma concentration 24 hours post-administration, during which patients are counseled they may experience some withdrawal symptoms as buprenorphine slowly displaces full agonist opioids from the opioid receptors.5 Patients are prescribed supportive medications for withdrawal management and counseled about the risks and benefits of using small amounts of their own non-prescribed opioid supply during the first 24 hours post-injection. Patients return one week later to receive a monthly injection.

Patients largely received rLAIB at two sites: the Comprehensive Health Care Center (CHCC) and OnPoint NYC (OPNYC). CHCC is a federally qualified health center located in the Bronx, NY, an urban area with high rates of poverty and opioid overdose deaths. OPNYC is a large harm reduction organization with the United States' first publicly recognized overdose prevention centers as well as co-located drug user health clinics.

Our case series includes 13 patients, the majority of whom were male (62%), middle aged (median age 39), and currently injecting non-prescribed opioids (N=7, 54%). Four (30.8%) patients identified as non-Latinx white, one (7.7%) patient as non-Latinx Black, three (23.1%) patients as non-Latinx of other race, and five (38.5%) as Latinx of any race. Ten (77%) patients had a documented history of SL-BUP treatment, and three (23.1%) patients had unsuccessfully attempted outpatient SL-BUP initiations, reporting this as their motivation for rLAIB. Time since last non-prescribed opioid use prior to rLAIB ranged from less than one hour to 21 hours. All patients had a COWS score of less than 8 prior receiving rLAIB, and nine (69.2%) had a COWS score of 4 or less. Nine (69.2%) patients received weekly Brixadi 32mg. Seven (53.8%) patients received rLAIB at OnPoint NYC, and six patients received rLAIB at CHCC.

Ten (76.9%) patients reported mild withdrawal symptoms after receiving rLAIB that subsided within a few days. Two (15.4%) patients reported that they did not have withdrawal symptoms. One patient was administered SL-BUP immediately after receiving rLAIB and experienced precipitated withdrawal. Seven (53.8%) patients received a second LAIB dose. Nine (69.2%) patients attended a follow-up appointment after receiving rLAIB.

Conclusion & Discussion: Our findings support rLAIB as a promising, novel approach to buprenorphine initiation in the outpatient setting. All but one patient tolerated rLAIB well, with either no withdrawal symptoms or mild symptoms that were self-managed, and high percentages received a second injection and returned for follow-up. The patient who experienced precipitated withdrawal did so after SL-BUP was administered immediately after LAIB, which informed our protocol moving forward to advise patients against SL-BUP use in the first 24 hours.

Our rLAIB protocol allows patients to start LAIB when they present to care and are interested in treatment, without requiring that they be in opioid withdrawal or already taking SL-BUP. This is critical in low-threshold settings such as OnPoint NYC where timely treatment initiation is key. rLAIB also obviates the need for patients to follow complex low-dose SL-BUP initiation protocols which often take several days and risk loss-to-follow-up. The high percentage of patients returning for subsequent injections and follow-up appointments indicates acceptability of rLAIB to patients. rLAIB provides an innovative, patient-centered, streamlined pathway for individuals at high risk for fatal overdose to initiate buprenorphine in the fentanyl era.

References: 1. Tanz LJ, Stewart A, Gladden RM, Ko JY, Owens L, O’Donnell J. Detection of Illegally Manufactured Fentanyls and Carfentanil in Drug Overdose Deaths — United States, 2021–2024. MMWR Morb Mortal Wkly Rep 2024;73:1099–1105. DOI: 10.15585/mmwr.mm7348a2

‌2. Weimer M, Herring AA, Kawasaki S, Meyer M, Kleykamp BA, Ramsey KS. ASAM Clinical Considerations: Buprenorphine Treatment of Opioid Use Disorder for Individuals Using High-potency Synthetic Opioids. J Addict Med. Published online July 28, 2023. doi:10.1097/adm.0000000000001202

3. Lofwall MR, Walsh SL, Nunes EV, et al. Weekly and Monthly Subcutaneous Buprenorphine Depot Formulations vs Daily Sublingual Buprenorphine With Naloxone for Treatment of Opioid Use Disorder. JAMA Intern Med. 2018;178(6):764. doi:10.1001/jamainternmed.2018.1052

4. D’Onofrio G, Herring AA, Perrone J, et al. Extended-Release 7-Day Injectable Buprenorphine for Patients With Minimal to Mild Opioid Withdrawal. JAMA Netw Open. 2024;7(7):e2420702. doi:10.1001/jamanetworkopen.2024.20702

5‌. Blair HA. Buprenorphine extended-release injection (Brixadi®) in the management of opioid use disorder: a profile of its use in the USA. Drugs Ther Perspect. Published online March 15, 2024. doi:10.1007/s40267-024-01055-y