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Substantial Impairment of Voriconazole Clearance by High-Dose Meropenem in a Patient With Renal Failure
Mazyar Mahmoudi1, Thorsten Brenner2, Gencay Hatiboglu3
1Departments of Clinical Pharmacology and Pharmacoepidemiology.
Abstract:
A critically ill patient with multiple postoperative infections repeatedly required profound voriconazole dose reductions whenever high-dose meropenem was added. Subsequent in vitro assessment confirmed inhibition of cytochrome P450 (CYP) 2C19 and CYP3A4 by meropenem, suggesting that during meropenem treatment, narrow therapeutic index drugs metabolized by these CYPs require close monitoring.
Insights
Meropenem can significantly reduce doses of voriconazole, an antifungal drug, by inhibiting key liver enzymes. This interaction necessitates careful monitoring of patients on both medications to prevent adverse events.
Area of Science:
- Clinical Pharmacology
- Infectious Diseases
- Drug Metabolism
Background:
- Critically ill patients often require broad-spectrum antibiotics like meropenem.
- Voriconazole is a crucial antifungal agent with a narrow therapeutic index.
- Drug-drug interactions can complicate treatment in critically ill patients.
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