Metamizole induces voriconazole metabolism and results in subtherapeutic voriconazole concentrations

AIMS: Voriconazole is extensively metabolized via cytochrome P450 (CYP) enzymes, predominantly CYP2C19 and CYP3A4. Drugs influencing the activity or expression of CYP enzymes can cause clinically relevant changes in the metabolism and voriconazole exposure. Metamizole is known to induce CYP3A4 and CYP2C19. This study aimed to investigate the pharmacokinetic drug-drug interaction between metamizole and voriconazole.

METHODS: In this single-centre retrospective observational cohort study, we compared voriconazole serum trough concentrations before, during and after metamizole treatment.

RESULTS: In the 9 included patients, the median voriconazole trough concentration decreased by 71% during metamizole treatment (P = .028) compared to before start of metamizole. The concentration/dose ratio similarly decreased by 81% during metamizole treatment (P = .018). Additionally, the metabolic ratio (voriconazole-n-oxide/voriconazole) increased from 0.9 to 2.4 (P = .028) during metamizole treatment. Subtherapeutic voriconazole trough concentrations were more frequent when combined with metamizole (before 14%, during 70%, after 17%).

CONCLUSIONS: Metamizole increases voriconazole metabolism and decreases voriconazole trough concentrations, probably through a CYP3A4 and CYP2C19 inducing effect. It is recommended to avoid concurrent use of metamizole and voriconazole or to closely monitor voriconazole trough concentrations during metamizole treatment and up to 2 weeks after discontinuation of metamizole.