Voriconazole potentiates warfarin-induced prothrombin time prolongation

Area of Science:

• Pharmacology and Drug Interactions
• Clinical Pharmacy
• Antifungal and Anticoagulant Therapy

Background:

• Voriconazole is a broad-spectrum antifungal agent.
• Warfarin is a commonly prescribed anticoagulant.
• Both drugs are metabolized by cytochrome P450 enzymes, suggesting potential interactions.

Purpose of the Study:

• To investigate the effect of voriconazole on the pharmacodynamics of warfarin.
• To assess the safety and tolerability of coadministering voriconazole and warfarin.
• To measure prothrombin time changes as an indicator of warfarin's effect.

Main Methods:

• A double-blind, placebo-controlled, two-way crossover study.
• Healthy male subjects received voriconazole or placebo with warfarin.
• Prothrombin time was measured to assess warfarin's anticoagulant effect.

Main Results:

• Coadministration of voriconazole with warfarin resulted in a statistically significant increase in prothrombin time.
• The mean maximum change and area under the effect curve for prothrombin time were significantly greater with voriconazole.
• Elevated prothrombin times persisted for up to 144 hours post-warfarin dose when coadministered with voriconazole.

Conclusions:

• Voriconazole potentiates warfarin's effect, leading to prolonged prothrombin times.
• Regular prothrombin time monitoring is crucial when voriconazole and warfarin are used together.
• Dose adjustments of warfarin may be necessary during coadministration.