Rapid extended-release buprenorphine induction without sublingual stabilization in a shelter-based harm reduction setting for high-risk fentanyl use: a retrospective case series

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Individuals with opioid use disorder (OUD) who use illicit fentanyl in shelter-based settings face profound barriers to conventional medications for OUD (MOUD), including requirements for sublingual buprenorphine (SL-BUP) stabilization prior to extended-release injectable buprenorphine (XR-BUP) initiation. We report the safety and preliminary outcomes of a novel rapid XR-BUP induction protocol—without prior SL-BUP stabilization or required opioid abstinence—in a low-barrier, virtual-care harm reduction program. This retrospective case series examined all individuals ( n = 21) receiving at least one off-label XR-BUP injection between October 1, 2023, and April 30, 2024, through Alberta’s Virtual Opioid Dependency Program (VODP) in partnership with two harm reduction program sites offering supervised consumption and/or shelter-based housing. Eligibility required an OUD diagnosis (DSM-5), high clinical risk for recurrent overdose, prior buprenorphine exposure without allergy, and no history of substance-induced seizure. All participants were actively using illicit fentanyl (self-report, verified against provincial electronic medical records) and received 300 mg XR-BUP within 24 h of intake without prior SL-BUP stabilization. Primary outcomes were: (1) change in monthly opioid overdose (OD) incidence rates pre- versus post-treatment; (2) XR-BUP retention; and (3) adverse events. Secondary outcomes included self-reported fentanyl use change and adjunct medications. A Wilcoxon signed-rank test evaluated OD rate changes. All 21 participants were using fentanyl at intake; seven within four hours of injection. No serious adverse events or deaths occurred; two participants (10%) had mild, self-resolving symptoms. Monthly OD rates decreased significantly from a mean of 0.87 ODs/month pre-treatment to 0.08 post-treatment (Z = − 3.54, p = 0.0004). 57% ( n = 12) received at least one maintenance dose; 38% ( n = 8), 19% ( n = 4), and 10% ( n = 2) received two, three, and four maintenance doses, respectively. Mean total doses was 2.24; 75% returning for maintenance did so within 42 days. 62% reported reduced fentanyl use post-treatment. Rapid XR-BUP induction without SL-BUP stabilization was safe and associated with significant OD rate reductions in a shelter-based harm reduction setting. To our knowledge, this is the first case series describing this protocol in a harm reduction shelter context via virtual care. Larger prospective studies are needed to confirm these findings and optimize rapid induction protocols.