(53) Rapid Low-Dose – High-Dose Buprenorphine Initiation Using PO Methodology - Case Series

Background & Introduction: In the era of fentanyl, avoiding buprenorphine precipitated opioid withdrawal (BPOW) in patients seeking treatment for opioid use disorder (OUD) is a major and ongoing concern. Evidence indicates that buprenorphine is an effective medication in the maintenance treatment of OUD, specifically at high doses (≥16mg)1. There have been various initiation methods described in the literature involving different dosing and modalities, with a growing body of evidence supporting predominantly low-dose (≤0.5mg) initiation methods.2-3 However, there are significant barriers to these methods that prevent community-based inpatient and outpatient treatment facilities from using them (e.g., inability to cut pills/films to allow low-dose administration, withdrawal length of time, using opioid agonist, and buprenorphine formulations not approved in the US for treatment of OUD such as transdermal, intravenous or buccal). This current case series provides additional evidence of the effectiveness of utilization of oral administration (PO) of buprenorphine4. This methodology takes advantage of the low oral bioavailability ( < 15%) due to the extensive first-pass effect5 for the low dose administration, and decreases the time from last fentanyl use to buprenorphine 16mg within 35-72 hours by repeated and escalading dose of buprenorphine (i.e., rapid low dose – high dose buprenorphine initiation).

Case Description: Sample: N=10 patients (Mage = 19.77; male = 92.31%) across 13 admissions from January-September 2023 were initiated on buprenorphine using rapid low dose – high dose PO buprenorphine protocol and met all inclusion/exclusion criteria for the protocol. Average COWS before first dose was 4.23 (range 1-8). Most (76.92%) reported using fentanyl solo or in combination with other opioids and 100% tested positive for fentanyl on urine drug screening; other primary opioids used in this sample included heroin and oxycodone. Two patients reported a history of multiple and significant BPOW when attempting to start buprenorphine in the past. Protocol: This protocol directed low dose buprenorphine/naloxone (January-April) or buprenorphine monoproduct (May-onward). On day 1 of protocol (8 patients initiated < 24 hours from last fentanyl use, and 5 patients initiated 24-48 hour from last fentanyl use), patients received 2mg PO at hour 0, 2mg PO at hour 3, 4mg PO at hour 6, 8mg PO at hour 9. On day 2 (within 35-72 hours of last fentanyl use), patients received buprenorphine 16mg sublingual at 8AM. Inclusion Criteria: 1) Positive urine toxicology for fentanyl; 2) COWS at time of initiation ≤8; 3) Initiation started within 48 hours from last fentanyl use. Exclusion Criteria: 1) Receiving extended-release buprenorphine subcutaneous injection at any time in the past. Outcomes: The protocol was initiated and completed successfully in 12 patients (success rate = 92.31%). One patient had worsening withdrawal after the first PO dose (COWS increased from 7 to 10) and decided to wait till the next day to initiate. However next day his COWS remained at 1 and he declined further dosing. All patients who completed the protocol tolerated the initiation well and reported favorable experiences with the protocol, including the 2 patients with significant history of BPOW, one of whom described this as “the best experience of my life”. Important to note that the one person who developed worsening withdrawal symptom received buprenorphine/naloxone combination product. None of the patients receiving buprenorphine monoproduct developed any withdrawal symptoms.

Conclusion & Discussion: This case series successfully adds evidence for utilizing a rapid PO buprenorphine initiation for patients presenting with severe fentanyl use history, including history of BPOW. This protocol allowed for the successful initiation on buprenorphine from fentanyl with a comparable success rate to other protocols currently being used. This methodology is effective at 1) reducing the duration of withdrawal symptoms until full dose of buprenorphine is initiated, 2) reducing BPOW, 3) removing barriers experienced by community-based inpatient addiction centers, including the inability to cut tablets/films, lack of access to opioid agonists as well as transdermal, IV or buccal formulations of buprenorphine due to regulatory restrictions. While this methodology needs further research, this protocol can be easily replicated in other inpatient treatment centers. Staff can be easily trained to deliver the initially low-dose PO buprenorphine and then transfer to a high-dose sublingual dose with relative ease. Effectiveness may vary on how patients present to the facility (e.g., already experiencing withdrawal, different amount/types of opioid use). Nevertheless, this case series demonstrates that this protocol is a viable methodology for inpatient facilities who want to implement low dose buprenorphine initiation but have limitations on the dosing and formulations of buprenorphine they can dispense.

References: 1. Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No.: CD002207.
2. Weiner MB, Guerra M, Morrow G, Adams K. Hospital-based buprenorphine micro-dose initiation. Am Soc Add Med. 2021;15(3):255-257.
3. Button DB, Hartley J, Robbins j, et al. Low-dose buprenorphine initiation in hospitalized adults with opioid use disorder: A retrospective cohort analysis. Am Soc Add Med. 2022;16(2): e105-e111.
4. Hakimi E, Chava A, Hathaaway DB, Suzuki J. “PO Buprenorphine” An alternative method of buprenorphine Initiation: A case report. ASAM Conference Poster Presentation. 2022; Hollywood, Florida.
5. Brewster D, Humphrey MJ, Mcleavy MA. The systemic bioavailability of buprenorphine by various routes of administration, Journal of Pharmacy and Pharmacology, Vol 33, Issue 1, September 1981, Pages 500-506.