(109) “P.O. Buprenorphine” - An Alternative Method of Buprenorphine Initiation: A Case Report

Background: Buprenorphine-precipitated opioid withdrawal has emerged as a major barrier to initiating buprenorphine-naloxone, a potentially life-saving treatment for persons with opioid use disorder (OUD). One recent nationwide survey suggests that at least one-in-five persons attempting to start buprenorphine within 24-hours of their last fentanyl use will experience precipitated withdrawal (1). To address such concerns, low-dose buprenorphine initiation (aka, “micro-dosing”) has emerged as an effective strategy. While various protocols exist, transdermal (TD), buccal (BUC) or sublingual (SL) tablet/film administration are all reported (2). However, no prior reports have discussed the possibility of using the oral (PO) route. This report describes a case of a successful, but inadvertent, oral administration of buprenorphine that points to the possibility of this approach.

Case Description: A 57-year-old man with a history of OUD, previously treated with buprenorphine-naloxone, was admitted to an academic medical center for poorly controlled pain following a revision of a left total knee arthroplasty. He was started on hydromorphone 10mg PO every 3 hours with adequate pain control. His buprenorphine-naloxone films had been discontinued prior to his latest surgery. He requested to re-initiate on buprenorphine before discharge. Per hospital protocol, 10 hours after last dose of hydromorphone, patient received buprenorphine-naloxone 2.0-0.5 mg tablet (COWS 16 prior to administration) followed by another 2.0-0.5 mg an hour from the first dose (COWS 13 prior to administration), and then an hour later an additional 4.0-1.0 mg (COWS 4 after administration). However, due to lack of familiarity of both the patient and his nurse with the sublingual administration of buprenorphine tablets, the medication was administered not sublingually but orally. After patient was informed of the error he recalled that, in comparison to his usual home buprenorphine-naloxone administration of SL films, the PO tablets resulted in “delayed” improvement in his withdrawal symptoms. Patient also reported significant improvement in pain one hour after the third dose. That evening, the patient was started back on his home dose. At the time of discharge, he reported near-complete resolution of his knee pain and denied any opioid withdrawal symptoms.

Discussion: Although inadvertent, and not as a low-dose initiation, the patient successfully initiated buprenorphine-naloxone via oral administration. Orally administered buprenorphine may be advantageous for use in low-dose initiation protocols for a number of reasons. First, prior studies suggest that PO buprenorphine is associated with poor bioavailability ( < 15%) due to extensive first-pass effect (4), providing lower plasma concentrations. This low bioavailability, may also eliminate the need to split the tablet/film, which can be problematic in both inpatient and outpatient settings. Second, using the tablet/film avoids using buprenorphine formulations not approved in the US for treatment of OUD such as transdermal or buccal, which is a barrier in outpatient low dose initiation. Indeed, the PO route has been used instead of the SL route for those who cannot tolerate it due to adverse effects (5). Nevertheless, more research is needed to establish the optimal strategies, feasibility and safety of PO buprenorphine for use in low-dose initiation protocols.

Conclusion: The case illustrates the successful initiation of buprenorphine via the oral route. Further research is needed to assess whether orally administered buprenorphine can safely function as a low-dose initiation strategy.

References: (1) Varshneya NB, Thakrar AP, Hobelmann JG, Dunn, KE, Huhn, As. Evidence of Buprenorphine-precipitated Withdrawal in Persons Who Use Fentanyl, Journal of Addiction Medicine: November 23, 2021 - Volume – Issue -doi: 10.1097/ADM.0000000000000922
(2) Button D, Hartley J, Robbins J, Levander XA, Smith NJ, Englander H, Low-dose Buprenorphine Initiation in Hospitalized Adults With Opioid Use Disorder: A Retrospective Cohort Analysis. Journal of Addiction Medicine, 17 May 2021,DOI: 10.1097/adm.0000000000000864
(3) “Hydromorphone: Drug Information.” Lexicomp. https://www.uptodate.com/contents/hydromorphone-drug-information.
(4) Brewster D, Humphrey MJ, Mcleavy MA. The systemic bioavailability of buprenorphine by various routes of administration, Journal of Pharmacy and Pharmacology, Volume 33, Issue 1, September 1981, Pages 500–506, https://doi.org/10.1111/j.2042-7158.1981.tb13848.x
(5) Nazari A, Naderi Mazjin S, Shamsipour M. Unusual Route of Buprenorphine Administration: An Alternative Approach for Bypassing Adverse Drug Reactions. Curr Ther Res Clin Exp. 2019;90:17-19. Published 2019 Jan 18. doi:10.1016/j.curtheres.2019.01.001