(101) Induction onto Buprenorphine Utilizing Transdermal Patches Over 24-48 Hours: IPPAS Method

Background & Introduction: North America has been grappling with a tragic overdose crisis for several years (1). In response, there have been major efforts to curb this crisis. Opioid agonist treatment plays a crucial role in the comprehensive care of patients with opioid use disorder. Buprenorphine, a first-line medication for this condition, is widely used due to its relatively safer profile, attributed to its partial agonistic effects on the mu-opioid receptor. However, this feature can also lead to the risk of precipitated withdrawal, complicating the induction process (2). Numerous innovative methods have been developed to facilitate the induction to Buprenorphine, eliminating the need for patients to be in withdrawal prior to induction, and these methods have seen widespread use (3, 4). Innovation in this field continues to optimize this process. This team previously reported a case where a patient with opioid use disorder was successfully induced onto a therapeutic dose of sublingual buprenorphine, utilizing a transdermal patch over 48 hours (5). Here, we present a retrospective chart review of patients with opioid use disorder using unregulated fentanyl who were induced onto a therapeutic dose of either sublingual buprenorphine/naloxone or subcutaneous buprenorphine depot, using this method, over a period of 24 to 48 hours.

Methods: We obtained ethics approval and conducted a retrospective chart review on 51 inpatients with fentanyl use disorder previously consented and treated with one of three experimental transdermal buprenorphine induction protocols while under our service, between January 1 2022 and November 31 2023. We have previously reported on these protocols in case reports.
The induction protocols used staggered cumulative application of 20ug/h buprenorphine transdermal patches over 48 hours (6 patches per 24h) or 24 hours (6 patches per 12h, or 4 patches per 8h). As opioid requirements in fentanyl-using patients are often not met with only buprenorphine during the initial titration phase, patients may continue to use unregulated opioids until their requirements are met by the OAT medication. Oral hydromorphone 16-32mg was also ordered for every 2 hours as needed to ensure opiate requirements were met while patients lost access to their own supply. Immediately after induction, patients were started on therapeutic-dose sublingual or injection buprenorphine and all patches were removed. Withdrawal symptoms were tracked during induction and several hours following full-dose buprenorphine start.

Results: Preliminary analysis of 51 patients show that precipitated withdrawal was rare. 46 patients experienced no withdrawal symptoms during or after induction. Among the remaining 5 patients, withdrawal lacked any objective signs (2 patients), was associated with low use of full agonist opiates during induction (2), or was confounded by concurrent psychosis and hyperactive delirium (1).
There were no serious adverse events that required withdrawal from the protocol. Only 10 patients were not successfully transitioned to injection or sublingual buprenorphine treatment. Reasons were: later opted for methadone (3), later opted for detox (1), buprenorphine injection too painful (1), order for medication was missing (1), withdrawal (2), and no reason given (2).
Mean oral hydromorphone equivalents used ranged from 8.9 mg to 19.3 mg per 12h interval while or after receiving patches, depending on protocol. Medians ranged from 6mg to 8mg per 12h interval. Usage of non-opiate withdrawal management medications was essentially none.
We have recently been approved to expand the date range by 1 year earlier for patients who received the experimental transdermal buprenorphine patch induction and have an additional 29 patients undergoing data collection to increase study power, and anticipate completion of this component and secondary outcomes analysis and manuscript submission by the date of the conference.

Conclusion & Discussion: Here, we presented a case series of 51 patients who were induced onto opioid agonist treatment with buprenorphine (sublingual and subcutaneous depot forms) using transdermal buprenorphine patch. The findings indicate that patients with high opioid tolerance, particularly those using unregulated fentanyl, can be effectively induced onto buprenorphine with minimal withdrawal symptoms. No major adverse events were captured. This method shows promise, similar to previous rapid induction techniques using micro-dosing, as it eliminates the need for patients to be in withdrawal prior to induction (3, 4). Additionally, it simplifies the dosing regimen, reduces nursing workload, and shortens the induction period. We speculate that this induction approach could be particularly beneficial in outpatient settings due to its ease of use compared to other low-dose induction methods. Further research is necessary to evaluate the effectiveness and safety of this approach in a larger patient population. If proven effective, this method could lead to a reduction in dropout rates during the induction phase, improve the completion rate of the induction process, and ultimately enhance retention in treatment and overall treatment outcomes.

References: 1. Understanding the Opioid Overdose Epidemic | Opioids | CDC [Internet]. Atlanta (GA): Centers for Disease Control and Prevention; [cited 2024 Jan 21]. Available from: https://www.cdc.gov/opioids/basics/epidemic.html
2. American Society of Addiction Medicine. National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use. Am Soc Addict Med. 2015;33:27-43.
3. Spreen LA, Dittmar EN, Quirk KC, Smith MA. Buprenorphine initiation strategies for opioid use disorder and pain management: A systematic review. Pharmacother J Hum Pharmacol Drug Ther. 2022;42(5):411-27.
4. De Aquino JP, Parida S, Sofuoglu M. The Pharmacology of Buprenorphine Microinduction for Opioid Use Disorder. Clin Drug Investig. 2021 May;41(5):425-36. doi:10.1007/s40261-021-01032-7.
5. Azar P, Wong JSH, Mathew N, Vogel M, Perrone J, Herring AA, et al. 48-Hour induction of transdermal buprenorphine to sublingual buprenorphine/naloxone: the IPPAS method. J Addict Med. 2023;10–1097.