New advances in extended-release buprenorphine therapy for opioid use disorder

With more than 53,000 apparent opioid toxicity deaths reported in Canada between January 2016 and June 2025, opioid use and toxicity are major public health concerns in our communities.1 Fortunately, a plethora of evidence exists for the use of opioid agonist therapy (OAT) in the treatment of opioid use disorder (OUD), leading to a variety of positive outcomes including reduced mortality and reduced opioid use.2,3 Within available OAT options, buprenorphine stands out due to its superior safety profile compared to methadone; namely, it is associated with lower mortality rates across multiple meta-analyses and cohort studies.2,3 Buprenorphine is also generally associated with fewer side effects such as cardiac arrhythmias and sexual dysfunction. That said, methadone demonstrates higher treatment retention rates compared to buprenorphine, leading to the inclusion of both drugs within guidelines as first-line OAT options.2,3Adherence is often a concern for many patients requiring OAT, with initial daily observed dosing and stringent missed-dose protocols presenting as significant barriers to optimal OAT treatment. The advent of extended-release buprenorphine (Bup-XR) injection aims to significantly reduce these barriers, and has changed OAT practice dramatically over the last several years. The ubiquity of OUD and OAT in daily practice positions pharmacists as important healthcare practitioners who can help patients and other clinicians navigate the rapid developments and changes in practice with Bup-XR.The basicsBup-XR is indicated for the treatment of moderate to severe OUD, as part of a complete treatment plan that includes counselling and psychosocial supports.4 Multiple Bup-XR products exist, but availability in Canada is limited to the monthly subcutaneous (SC) injection, Sublocade.Evidence for Sublocade shows increased retention and abstinence rates when compared with placebo.3 Longitudinal studies support treatment retention and abstinence for up to 12 months in those maintained on Sublocade.3 A 24-week head-to-head trial of a different SC Bup-XR formulation vs. sublingual buprenorphine–naloxone showed non-inferiority in unregulated opioid use as measured by self-report and urine drug tests.5Traditionally, transition to Bup-XR required stabilization on transmucosal buprenorphine (most commonly SL buprenorphine–naloxone) between the doses of 8–24 mg/day for a period of seven days or more.4 The SC injection was originally approved to be administered in the abdominal area only. It must be prescribed and administered by certified healthcare practitioners. Certification of prescribers and providers is done through a manufacturer program. Across Canada, some jurisdictions have already approved or are working towards expanding the scope of certified pharmacists to include the administration of Sublocade.6 Sublocade is only distributed via a controlled distribution process, which requires dispensing pharmacies to register with the manufacturer.4Until recently, loading doses (two 300 mg doses administered one month apart) were required when transitioning to Sublocade.4 Thereafter, 100 mg maintenance doses every month are recommended in the product monograph,4 but can be either 100 mg or 300 mg depending on patient presentation. A minimum of 26 days is required between doses. Clinical trials show no significant differences in efficacy between 100 mg and 300 mg maintenance doses, but 300 mg doses are associated with more adverse events.4 Nonetheless, the prevalence of high-potency fentanyl use in many of our patients often necessitates 300 mg maintenance doses in practice.New developmentsThe pervasiveness of high-potency fentanyl has led to increased clinical needs in many OUD patients. In response, rapid developments in Bup-XR practice have emerged. Health Canada and the US Food and Drug Administration have recently approved updates to the product monograph and labelling for Sublocade, designed to reflect current clinical practice and enable increased convenience and uptake by patients in need.4,7 Transition to Sublocade now only requires a single ‘test dose’ of transmucosal buprenorphine (typically 4 mg following standard transmucosal buprenorphine induction protocols) to ensure tolerability and clinical stability, reflecting emerging evidence in this area.4,7 The second 300 mg loading dose of Sublocade can also now be administered one week after the initial loading dose. This is designed to increase treatment retention and rapidly achieve therapeutic buprenorphine levels.4,7,8Further, administration sites for Bup-XR have now been expanded to include SC tissue areas in the thigh, buttock and back of the upper-arm, in addition to the abdominal area (Figure 1).4 This is supported by a 2024 study showing comparable buprenorphine plasma exposure (AUC) following administration at the various sites.9 Of note, administration in the thigh and upper-arm areas produced peak plasma concentrations (Cmax) that were 52% and 39% higher, respectively, compared to administration in the abdomen. That said, the higher Cmax was not associated with increased adverse events in the study.9 Nevertheless, pharmacists should actively follow up with these patients to monitor for adverse effects, particularly about 24 hours after administration (Tmax).To provide additional dosing flexibility, guidance now recommends that occasional dose delays of up to four weeks (i.e., 56 days after last injection) after steady state has been achieved are not expected to have significant clinical effects and dosing can be resumed without reinduction, as therapeutic levels are likely to be maintained.10 Of course, the patient should be assessed to ensure clinical appropriateness for resumption, with particular cautions around over-sedation and precipitated withdrawal risks, especially if the patient has used any other opioids in the interim.Some patients may continue to experience cravings or withdrawal symptoms after Bup-XR administration, particularly during the initial induction period. In these situations, guidelines recommend short-term use of supplemental transmucosal buprenorphine doses of < 8 mg daily for up to 14 days.10 In practice, supplemental transmucosal buprenorphine doses may be continued for longer and at higher doses on a case-by-case basis.SummaryWith recent developments in dosing and administration site recommendations for extended-release buprenorphine injection, pharmacists should remain vigilant to rapidly-changing practices and help guide other clinicians and patients in Bup-XR use.Sunny Wang, RPh, PharmD, is a clinical pharmacist at the Centre for Addiction and Mental Health (CAMH) in Toronto, ON. He is also a clinical instructor at the Leslie Dan Faculty of Pharmacy and serves as an expert hub member for the Addiction Medicine and Psychosocial Interventions Program with Project ECHO.References:Government of Canada. Opioid- and stimulant-related harms in Canada; Last updated: December 11, 2025.Canadian Research Initiative in Substance Matters. Update to national guideline of the Canadian Research Initiative in Substance Matters for the clinical management of opioid use disorder. 2024.British Columbia Centre on Substance Use. BC Ministry of Health, and BC Ministry of Mental Health and addictions. A guideline for the clinical management of opioid use disorder. November 2023. (accessed March 19, 2026).Indivior UK Limited. Sublocade (buprenorphine solution [extended-release] for injection) product monograph. Hull, UK; December 2, 2025. (accessed March 20, 2026).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: a randomized clinical trial. JAMA Intern Med 2018;178(6):764-73. doi:10.1001/jamainternmed.2018.1052.Ontario College of Pharmacists. Expanding scope of practice; March 25, 2026. (accessed March 27, 2026).Indivior UK Limited. Sublocade (buprenorphine extended-release injection) prescribing information. Hull, UK; December 2025. (accessed March 4, 2026).Shiwach R, Le Foll B, Alho H, et al. Rapid vs standard induction to injectable extended release buprenorphine: a randomized clinical trial. JAMA Network Open 2025;8(10):e2537319. doi:10.1001/jamanetworkopen.2025.37319.Laffont CM, Lapeyra O, Mangal D, et al. A single-dose study to evaluate the relative bioavailability, safety, and tolerability of monthly extended-release buprenorphine at alternative injection locations in adult participants with opioid use disorder. Clin Drug Investig 2024;44(12):939-49. doi.org/10.1007/s40261-024-01406-7.Lintzeris N, Dunlop A, Schulz M. Long-acting injectable buprenorphine (LAIB) for opioid dependence treatment: practice guide (2nd Ed). NSW Ministry of Health: Sydney, AU; 2024.