We return to Mike who we met in two previous PsychSnaps focused on buprenorphine (see related PsychSnaps below). Mike has moderate opioid use disorder (OUD) and is maintained (and doing well!) on buprenorphine 16mg sublingual every morning. He has returned to work, which requires him to go into the office every day, and is continuing to improve his relationships with his girlfriend and family. His only complaint about the buprenorphine is that he forgets to take it 1-2x/week, which causes him to feel bad starting around lunchtime.
Are there any options for buprenorphine for patients with OUD (at least moderate severity) that don’t require daily administration?
At the end of 2017, the FDA approved a monthly, long-acting injectable version of buprenorphine (brand name Sublocade) for patients with OUD that is given subcutaneously by trained clinicians (Haight 2019). The clinics and/or pharmacies also need to be enrolled in a REMS program. In 2023, another subcutaneous option was approved by the FDA under the brand name Brixadi that can also be given as a weekly or monthly injection. Both medications block cravings, suppress withdrawal symptoms, and ensure significant mu opioid receptor occupancy at their treatment doses. Both–though Sublocade 300mg monthly in particular–are thought to achieve higher and more steady serum buprenorphine concentrations for longer than their sublingual counterparts (Greenwald 2023, Heidbreder 2023, Sublocade and Brixadi package inserts).
You review these long-acting injectable buprenorphine options with Mike. While there are two options on the market, your clinic has only been able to provide Sublocade reliably due to pharmacy and formulary constraints. Without insurance, but with cost saving, Brixadi (32mg dose) can cost about $715 a week and both doses of Sublocade cost about $2,000 a month. You discuss the evidence that supports switching Mike to a long-acting formulation of buprenorphine, including high treatment satisfaction, improved treatment retention, and improved quality of life (Ling 2020, Martin 2022). Mike decides to switch to long-acting injectable buprenorphine and asks what he should expect.
How do you initiate and follow a patient on long-acting injectable buprenorphine?
You think Mike would benefit from a switch to a long-acting injectable version of buprenorphine to help him with adherence, provide more flexibility with OUD treatment (fewer pharmacy/clinic visits and messages), and ensure steadier serum levels and lower peak-to-trough fluctuations than with daily dosing (Jones 2021).
You offer Sublocade to Mike and explain how the medication works. It’s a once monthly injection of a depot of buprenorphine, with the medication buprenorphine dissolved in a biocompatible solvent. When the liquid polymer system is injected subcutaneously in the abdomen (with a regular needle and syringe), it solidifies upon contact with body fluids to create a solid implant. The buprenorphine, as part of this polymer matrix, is slowly released into circulation as the polymer biodegrades during the month (Heidbreder 2023). It’s important not to touch the depot/injection site as manipulation may increase the release of buprenorphine into the plasma.
Getting the injection is relatively simple in a place with trained clinicians who administer the injection in the abdominal subcutaneous tissue. The biggest downside to long-acting, injectable buprenorphine (LAIB) in the form of Sublocade is that the injection burns and requires a large, 19 gauge needle. Experts recommend the use of ice, a local anesthetic spray, or lidocaine (3mL injected subcutaneously prior to Sublocade) to help with the burning. The benefit of Brixadi is that it is injected with a smaller needle, causes less burning with injection, creates less of a lump, and can be injected in the arm and thigh in addition to the abdomen. Some data show that the mean buprenorphine levels at steady state for Sublocade 300mg are higher than what is achievable with the highest Brixadi dose (Sublocade vs Brixadi Comparison Table; package inserts for both).
When transitioning patients from sublingual bup to long-acting injectable buprenorphine, most clinicians follow the formal instructions in the package insert from the company that makes Sublocade: a patient should take at least 7 days of their sublingual buprenorphine dose (at least 8mg) prior to the injection. Some clinicians in emergent care settings may chose to administer the injection after at least one dose of sublingual buprenorphine is tolerated by a patient.
Mike has been on bup 16mg daily for months. After securing insurance authorization for Sublocade, you prepare him for the typical dosing schedule of the medication: 300mg dose for the first two months, then 100mg buprenorphine monthly for maintenance. The Sublocade injection doses don’t correlate 1:1 to a certain amount of sublingual buprenorphine over the month; the injection doses for initiation and maintenance were chosen based on receptor occupancy and craving blockade. Of note, patients who use fentanyl or who are on higher sublingual buprenorphine doses (e.g. 24mg) may require an ongoing Sublocade maintenance dose of 300mg, according to expert opinion. Recent trials suggest that the 300mg maintenance dosing is necessary to prevent return to use in patients injecting drugs (Greenwald 2023).
During the first few months on Sublocade, Mike may experience decreasing serum levels of buprenorphine at the end of month, resulting in cravings or withdrawal symptoms. You provide extra sublingual buprenorphine films for him to have on hand to use daily if he notices any symptoms, especially in the week before he gets his next shot. You schedule follow-up visits with Mike 1 week after the first injection and then monthly.
Key Points
- Long-acting injectable buprenorphine (LAIB) can improve medication adherence, treatment retention, quality of life, and treatment satisfaction for patients with opioid use disorder.
- LAIB in the form of Sublocade is safe and easy to administer subcutaneously monthly with the main side effect of injection site burning
Related PsychSnaps and Resources
How do you start buprenorphine for a patient with opioid use disorder? Era Kryzhanovskaya, June 2024.
How do you start buprenorphine for someone with fentanyl use disorder? Era Kryzhanovskaya, August 2024.
Package Inserts:
- Sublocade https://www.sublocade.com/Content/pdf/prescribing-information.pdf table 7/page 33
- Brixadi https://brixadi.com/pdfs/brixadi-prescribing-information.pdf table 7/page 37
Comparison Table of Brixadi and Sublocade, Accessed November 4th, 2024: https://www.smchealth.org/sites/main/files/file-attachments/brixadi_formulary_recommendation_to_hpsm.pdf?1689879826
References
Greenwald MK, Wiest KL, Haight BR, Laffont CM, Zhao Y. Examining the benefit of a higher maintenance dose of extended-release buprenorphine in opioid-injecting participants treated for opioid use disorder. Harm Reduct J. 2023 Dec 2;20(1):173. doi: 10.1186/s12954-023-00906-7. PMID: 38042801; PMCID: PMC10693082.
Haight BR, Learned SM, Laffont CM, Fudala PJ, Zhao Y, Garofalo AS, Greenwald MK, Nadipelli VR, Ling W, Heidbreder C; RB-US-13-0001 Study Investigators. Efficacy and safety of a monthly buprenorphine depot injection for opioid use disorder: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2019 Feb 23;393(10173):778-790. doi: 10.1016/S0140-6736(18)32259-1. Epub 2019 Feb 18. PMID: 30792007.
Heidbreder C, Fudala PJ, Greenwald MK. History of the discovery, development, and FDA-approval of buprenorphine medications for the treatment of opioid use disorder. Drug Alcohol Depend Rep. 2023 Jan 10;6:100133. doi: 10.1016/j.dadr.2023.100133. PMID: 36994370; PMCID: PMC10040330.
Jones AK, Ngaimisi E, Gopalakrishnan M, Young MA, Laffont CM. Population pharmacokinetics of a monthly buprenorphine depot injection for the treatment of opioid use disorder: A combined analysis of phase II and phase III trials. Clin Pharmacokinet. 2021;60: 527–540. doi.org/10.1007/s40262-020-00957-0
Ling W, Nadipelli VR, Solem CT, Ronquest NA, Yeh YC, Learned SM, Mehra V, Heidbreder C. Effects of monthly buprenorphine extended-release injections on patient-centered outcomes: A long-term study. J Subst Abuse Treat. 2020 Mar;110:1-8. doi: 10.1016/j.jsat.2019.11.004. Epub 2019 Nov 15. PMID: 31952623.
Martin E, Maher H, McKeon G, Patterson S, Blake J, Chen KY. Long-acting injectable buprenorphine for opioid use disorder: A systematic review of impact of use on social determinants of health. J Subst Abuse Treat. 2022 Aug;139:108776. doi: 10.1016/j.jsat.2022.108776. Epub 2022 Mar 25. PMID: 35365366.