Fluconazole-induced symptomatic phenytoin toxicity

Abstract

Objective: To report two cases of fluconazole-induced symptomatic phenytoin toxicity and review literature related to this interaction.

Data sources: Case reports and review articles identified by a computerized (MEDLINE) and manual (Index Medicus) search.

Data synthesis: Fluconazole is a broad-spectrum triazole antifungal agent primarily eliminated by renal mechanisms, although hepatic cytochrome P-450 inhibition and hepatotoxicity have been observed. We report two cases of fluconazole-induced symptomatic phenytoin toxicity. Both patients received high doses of the drug; one patient developed phenytoin toxicity only after long-term coadministration. Previously reported cases have occurred primarily with high-dose fluconazole and short-term coadministration.

Conclusions: Fluconazole can increase phenytoin serum concentrations leading to toxicity. Constant and continuous monitoring of serum phenytoin concentrations with fluconazole doses as low as 200 mg/d is warranted.