Micro-dosing Buprenorphine/Naloxone to Combat Fentanyl Withdrawal During Renal Failure

Case Description
A 48-year old man was admitted for anasarca and anuria secondary to membranoproliferative glomerulonephritis (MPGN) due to Hepatitis B and C secondary to injection drug use in setting of opioid use disorder (OUD). The patient endorsed using fentanyl and heroin daily intravenously, and urine drug screen revealed levels above the limit of quantification of morphine, fentanyl, norfentanyl, oxycodone, oxymorphone, and 6MAM/heroin metabolites. Addiction medicine was consulted for management of OUD in setting of chronic pain and renal failure resulting in decreased clearance of full agonists. The patient was started on the micro-dosing protocol of buprenorphine.1 The 8-day micro-dosing protocol gradually increased buprenorphine/naloxone dosing beginning with 0.5mg once daily on day one to 12mg daily on day eight. Agonists were continued until day 6. Concurrently, his renal failure was treated with a furosemide drip by the medical team, resulting in improved renal function. The patient reported adequate pain control while full agonists on the mu receptors were slowly replaced by buprenorphine. Despite his renal failure the patient tolerated the micro-dosing protocol well and did not experience any symptoms of withdrawal during the protocol or after discontinuation of full agonists. The patient endorsed transportation barriers to weekly clinic appointments and therefore, extended release buprenorphine was administered prior to discharge. Despite his complicated medical history, his OUD was treated during his admission while maintaining pain control and without causing precipitated withdrawal, and he was in early remission at time of discharge.

Discussion
Prior to initiation of buprenorphine, patients usually require a short period of mild to moderate opioid withdrawal (approximately 8-12 hours since the last dose of short-acting opioid), to prevent precipitated withdrawal.2 This case was challenging as the time required to develop opioid withdrawal was unclear in the setting of delayed renal clearance. The lipophilic property of fentanyl and the patient’s high BMI (>30) further complicated the appropriate timing for buprenorphine initiation.2,3 In addition, the patient was concerned about the withdrawal period due to chronic pain. Micro-dosing of buprenorphine/naloxone avoids precipitation of opioid withdrawal by providing a partial opioid agonist with high affinity to the mu opioid receptor that slowly replaces the full agonists.1,4 Our case demonstrates that micro-dosing can be successfully used in patients with decreased renal clearance. Starting buprenorphine extended release at discharge addresses the health inequity of living in a rural, underserved area.

Conclusion
This case illustrates a case of severe opioid use disorder in the setting of renal failure. Micro-dosing buprenorphine/naloxone is an effective treatment option to transition patients with renal failure to medication for OUD without causing precipitated withdrawal.

References: 1. Bruneau J, Goyer ME, Ahamad K, et al. Management of opioid use disorders: A national clinical practice guideline. CMAJ. 2018; 190(9): E247-E257.
2. Randhawa PA, Brar R, Nolan S. Buprenorphine-naloxone "microdosing": an alternative induction approach for the treatment of opioid use disorder in the wake of North America's increasingly potent illicit drug market. CMAJ. 2020 Jan 20;192(3): E73.
3. McClain DA, Hug CC Jr. Intravenous fentanyl kinetics. Clin Pharmacol Ther. 1980;28(1):106-14.
4. Hämmig R, Kemter A, Strasser J, von Bardeleben U, Gugger B, Walter M, Dürsteler KM, Vogel M. Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the Bernese method. Subst Abuse Rehabil. 2016; 7:99-105.

Learning Objective: To illustrate a case of severe opioid use disorder in the setting of renal failure using micro-dosing buprenorphine/naloxone as an effective treatment option to avoid precipitated withdrawal.