Skip to main content
After reviewing the article by Bruneau et al,(1) we agree that appropriate therapy should be used to manage opioid use disorders, with buprenorphine-naloxone (BUP/NX) being a first-line option. A significant limitation of the medication, however, is the need for an individual to abstain from opioid use for a period of time prior to BUP/BX initiation. Such a requirement is necessary to allow adequate time for the elimination of systemic full opioid agonists to avoid precipitation of opioid withdrawal with the use of BUP/NX (a partial opioid agonist with high affinity for the mu opioid receptor). In the current fentanyl era however, successfully achieving this ‘opioid washout’ can be a challenge. While fentanyl has a rapid onset and short duration of action, the substance itself is lipophilic resulting in distribution to the peripheral tissues in a manner that is not dose-dependent.(2, 3) Consequently, continuous and prolonged use of fentanyl can result in an increased volume of distribution systemically with slow dissipation overall.(2) Accordingly, the pharmacokinetics of fentanyl combined with its high prevalence in the illicit drug market appear (at least anecdotally) to be increasing the incidence of precipitated withdrawal during the BUP/NX induction process. This occurs despite patients objectively being in moderate to severe opioid withdrawal prior to initiation on the medication.
To address this, some prescribers in British Columbia (and likely beyond) are adopting a ‘micro-dosing’ approach for BUP/NX inductions. Officially recognized as the Bernese method,(4) ‘micro-dosing’ involves the prescribing of BUP/NX in a very small initial dose (e.g., 0.5/0.125 milligrams [mg]) with incremental increases to both dose and frequency over time (Table 1). Coinciding with this, patients can continue to use other opioids (either prescribed or illicit), until a therapeutic dose of BUP/NX has been achieved (e.g., usually >8 mg daily), at which point full opioid agonists are generally discontinued.(4) The entire induction process takes place over a 7 to 10 day period and has been associated with significant success. Individuals consistently report the induction process to be well-tolerated with a reduction or elimination of cravings and avoidance of precipitated withdrawal.(4, 5) While further research evaluating BUP/NX ‘micro-dosing’ is certainly needed (to date only 2 case reports and one small case series exist),(4, 5) adoption of this prescribing approach may offer a safe and effective alternate strategy for BUP/NX induction among individuals with an OUD. In the wake of an ever-changing illicit drug market, innovation (with simultaneous evaluation) is needed to help turn the tide on North America’s opioid crisis.
Table 1: Outpatient micro-dosing induction schedule for buprenorphine/naloxone.
Day 1: 0.5mg loading dose (0.5mg total)
Day 2: 0.5mg BID (1mg total)
Day 3: 1mg BID (2mg total)
Day 4: 2mg BID (4mg total)
Day 5: 3mg BID (6mg total)
Day 6: 4mg BID (8mg total)
Day 7: 12 mg (12mg and discontinue other opioids)
References:
1. Bruneau J, Ahamad K, Goyer M-È, Poulin G, Selby P, Fischer B, et al. Management of opioid use disorders: a national clinical practice guideline. Canadian Medical Association Journal. 2018;190(9):E247-E57.
2. McClain DA, Hug CC, Jr. Intravenous fentanyl kinetics. Clinical pharmacology and therapeutics. 1980;28(1):106-14.
3. Holley FO, van Steennis C. Postoperative analgesia with fentanyl: pharmacokinetics and pharmacodynamics of constant-rate i.v. and transdermal delivery. British journal of anaesthesia. 1988;60(6):608-13.
4. Hammig R, Kemter A, Strasser J, von Bardeleben U, Gugger B, Walter M, et al. Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the Bernese method. Substance abuse and rehabilitation. 2016;7:99-105.
5. Klaire S, Zivanovic R, Barbic SP, Sandhu R, Mathew N, Azar P. Rapid micro-induction of buprenorphine/naloxone for opioid use disorder in an inpatient setting: A case series. The American journal on addictions. 2019.