Injectable extended-release buprenorphine is an effective treatment for opioid use disorder (OUD), but injection site reactions (ISRs) are common treatment-emergent adverse events that may impact patient comfort, adherence, and outcome. This report examines the clinical presentation, prevalence, and management of Sublocade-related ISRs through two case studies and a review of existing literature.

We present two cases of ISRs in patients receiving extended-release buprenorphine, Sublocade. The first involves a 65-year-old male who experienced localized pain, swelling, and erythema after the injection. The second case features a 58-year-old male with injection site swelling, tenderness, and presumed cellulitis. We also examine ISR prevalence and severity from clinical trials and real-world data.

Both patients received timely care and responded well to appropriate interventions. The first case was managed conservatively with cold compresses, topical hydrocortisone, and ibuprofen, resulting in symptom resolution. The second case required oral antibiotics after ultrasound imaging revealed a subcutaneous fluid collection; the cellulitis resolved without systemic complications.

While ISRs associated with Sublocade are common, most are manageable with conservative interventions. Emphasizing patient education, proper injection techniques, and site rotation is essential to prevent ISRs, minimize their severity, and enhance treatment outcomes in patients with OUD.