Induction of Voriconazole Metabolism by Rifampin in a Patient with Acute Myeloid Leukemia: Importance of Interdisciplinary Communication To Prevent Treatment Errors with Complex Medications

Antimicrobial Agents and Chemotherapy
2007.0

Abstract

Voriconazole is metabolized by CYP450 isoenzymes 2C19, 3A4, and to a lesser extent CYP2C9, and coadministration with rifampin (a CYP450 inducer) can cause drug-drug interactions. In an ongoing study on the steady-state pharmacokinetics of voriconazole involving 31 hospitalized patients receiving voriconazole, we identified one patient with acute myeloid leukemia who was accidentally treated with the contraindicated combination of voriconazole and rifampin due to poor interdisciplinary communication (the clinical microbiologist was unaware of the patient's voriconazole therapy, and the treating physicians failed to check for drug-drug interactions). Pharmacokinetic analysis showed that after 30 days of rifampin treatment, the total voriconazole exposure was dramatically decreased by 99% (Cmax decreased from 3.92 μg/ml to 0.038 μg/ml, AUC0-12 decreased from 27.4 h·μg/ml to 0.145 h·μg/ml), while the plasma concentrations of voriconazole metabolites (N-oxide, hydroxyvoriconazole, dihydroxyvoriconazole) were similar or increased, with significantly elevated metabolic ratios, indicating rifampin-induced voriconazole metabolism. Since the antifungal effect of voriconazole depends on the parent drug, coadministration with rifampin leads to loss of efficacy. This case emphasizes the importance of interdisciplinary communication between treating physicians and consulting experts, as well as regular reviews of complex medication regimens, to prevent such treatment errors.

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