European journal of clinical pharmacology
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Eur. J. Clin. Pharmacol. · Mar 2015
Randomized Controlled TrialEffects of terbinafine and itraconazole on the pharmacokinetics of orally administered tramadol.
Tramadol is widely used for acute, chronic, and neuropathic pain. Its primary active metabolite is O-desmethyltramadol (M1), which is mainly accountable for the μ-opioid receptor-related analgesic effect. Tramadol is metabolized to M1 mainly by cytochrome P450 (CYP)2D6 enzyme and to other metabolites by CYP3A4 and CYP2B6. We investigated the possible interaction of tramadol with the antifungal agents terbinafine (CYP2D6 inhibitor) and itraconazole (CYP3A4 inhibitor). ⋯ Terbinafine may reduce the opioid effect of tramadol and increase the risk of its monoaminergic adverse effects. Itraconazole has no meaningful interaction with tramadol in subjects who have functional CYP2D6 enzyme.