Micro-Dosing Intravenous Buprenorphine to Rapidly Transition from Full Opioid Agonists

Introduction: Initiating buprenorphine for opioid use disorder can be difficult because of the risk of precipitating withdrawal in patients transitioning from methadone, requiring opioid analgesia, or with regular exposure to fentanyl. Guidelines recommend tapering methadone over days to weeks and waiting 36-72 hours before initiating buprenorphine. Many patients, especially those in the post-operative period, cannot tolerate the 8 hours without opioid analgesia required to transition from short-acting full opioid agonists. Finally, patients and clinicians increasingly report precipitated withdrawal in patients with repeat exposure to fentanyl despite waiting 24-72 hours before initiating buprenorphine, likely due to fentanyl's lipophilicity and protracted renal clearance. Low-dose initiation, also known as micro-dosing, is an alternative to standard initiation. Prior studies relied on non-standard dosing of tablets or films, patches, or buccal formulations, all of which are unavailable in many hospitals.

Methods: We report a novel approach to micro-dosing using intravenous buprenorphine. Intravenous buprenorphine was administered every six hours in escalating doses of 0.15 mg to 0.6 mg over three days before transitioning to sublingual buprenorphine. Patients were prescribed as-needed hydromorphone to treat pain, withdrawal, or craving during the transition period.

Results: Two patients were successfully transitioned to buprenorphine using three days of intravenous buprenorphine micro-dosing without precipitating withdrawal. One patient was rapidly transitioned from methadone and a second was transitioned from post-operative full-opioid agonists. Both patients used as-needed hydromorphone during the transition period.

Conclusions: A novel method of using intravenous buprenorphine micro-dosing and as-needed full-agonist opioids was successfully used to transition one patient from methadone maintenance and one patient from full-opioid agonist analgesia without precipitating withdrawal.

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