UMEM Educational Pearls

Title: CYP3A4 inducing agents may cause opioid withdrawal in patients on buprenorphine

Keywords: buprenorphine, CYP3A4, induction, inhibition, metabolism (PubMed Search)

Posted: 4/23/2020 by Hong Kim, MD
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Buprenorphine (BUP) is increasingly prescribed/used to treat opioid use disorder (OUD) in the United State. BUP is mainly metabolized by CYP3A4 where its enzymatic activity can be either induced or inhibited by many agents.

For example, a study showed that Rifampin administration for 15 days, a potent 3A4 inducer, resulted in (1):

Reduction of plasma BUP concentration (70% reduction in area under the curve [AUC])
50% of the study subjects (12 out of 24) experienced opioid withdrawal symptoms (OWS)
4 out of 12 who experience OWS received transient increase in their BUP dose (25-100%)

On the contrary, exposure to voriconazole – strong 3A4 inhibitor - resulted in (n=12 health volunteers) (2):

Increased the plasma BUP AUC by 4.3 fold
Increased peak BUP concentration by 3.9 fold
Documented adverse effects were dizziness and nausea only

Cannabis use – (CBD is a CYP 3A4 inhibitor) also increased the BUP concentration by 2.7 fold. (3)

Bottom line:

Be mindful of drug-drug interaction when initiating a new medication in patients with OUD on BUP
Inquire about any recent medication change in patients who may be experiencing OWS while on steady dose of BUP for their OUD.

References

1. Drug Alcohol Depend. 2011 Nov 1;118(2-3):326-34. doi: 10.1016/j.drugalcdep.2011.04.013. Epub 2011 May 19.

Rifampin, but not rifabutin, may produce opiate withdrawal in buprenorphine-maintained patients.

McCance-Katz EF¹, Moody DE, Prathikanti S, Friedland G, Rainey PM.

2. Eur J Clin Pharmacol. 2018 Dec;74(12):1615-1622. doi: 10.1007/s00228-018-2548-8. Epub 2018 Aug 30.

Voriconazole greatly increases the exposure to oral buprenorphine.

Fihlman M^1,2, Hemmilä T², Hagelberg NM^1,2, Backman JT³, Laitila J³, Laine K^4,5, Neuvonen PJ³, Olkkola KT⁶, Saari TI^7,8.

3. Eur Arch Psychiatry Clin Neurosci. 2020 Jan 6. doi: 10.1007/s00406-019-01091-0. [Epub ahead of print]

Buprenorphine-cannabis interaction in patients undergoing opioid maintenance therapy.

Vierke C¹, Marxen B², Boettcher M³, Hiemke C⁴, Havemann-Reinecke U^2,5.