Initiation and Dosing of Extended-Release Buprenorphine: A Narrative Review of Emerging Approaches for Patients Who Use Fentanyl

Kenneth W Lee,1 Annabel Mead,2 Imran Ghauri,3 Bruce Hollett,4 Martine Drolet,5 Jan-Marie Kozicky5 1Department of Family Medicine, Department of Psychiatry, Western University, London, ON, Canada; 2Correctional Health Services, BC Mental Health and Substance Use Services, Vancouver, BC, Canada; 3Alberta Health Services, Calgary, AB, Canada; 4Memorial University of Newfoundland, St. John’s, NL, Canada; 5Indivior, Montreal, QC, CanadaCorrespondence: Kenneth W Lee, London RAAM Clinic, Suite 260, 200 Queens Avenue, London, ON, N6A 1J3, Canada, Tel +1 519 280 7790, Email [email protected]: Individuals with Opioid Use Disorder (OUD) who use fentanyl are at high risk of mortality due to opioid-related overdose. While buprenorphine extended-release (BUP-XR) may reduce this risk, there is a need to optimize clinical practice with BUP-XR to overcome barriers to treatment initiation and retention in patients who use fentanyl. Through a narrative review of evidence from peer-reviewed publications and conference abstracts, this article provides an overview of current novel initiation and dosing strategies for BUP-XR in patient populations with confirmed or presumed use of fentanyl. Evidence in this area is rapidly emerging with multiple studies describing BUP-XR initiation prior to 7-day stabilization on transmucosal buprenorphine (TM-BUP). Results from a randomized controlled study indicate that initiating BUP-XR following a single TM-BUP dose is noninferior to standard initiation in terms of treatment retention at injection 2, with similar rates of precipitated withdrawal and adverse events, and this protocol is now included in the approved prescribing information in the USA. While additional “macro/high-dose” or “micro/low-dose” and “direct dose” induction approaches have also been reported, evidence for these is limited to small uncontrolled studies or case reports. Consistent with evidence from studies of TM-BUP, which suggests individuals who use fentanyl may require higher maintenance doses in order to be retained in treatment, administrative and observational data suggests that use of the 300-mg maintenance dose, shortened intervals between doses, and supplemental TM-BUP may be feasible approaches to increase buprenorphine exposure in patients with ongoing symptoms and improve retention. Evidence in this area is rapidly evolving, and many of these strategies are increasingly being adopted clinically and incorporated into clinical guidelines. Further research should incorporate increased sample sizes, broader and more consistent outcome measurement, and increased duration of follow-up to facilitate more robust evaluation of efficacy and safety as well as increase comparability between studies.Keywords: opioid use disorder, extended-release buprenorphine, long-acting buprenorphine, BUP-XR, fentanyl