FLUCONAZOLE-INDUCED SYMPTOMATIC PHENYTOIN TOXICITY

OBJECTIVE: To report two cases of fluconazole-induced symptomatic phen ytoin toxicity and review lite related to this interaction. DATA SOURC ES: Case reports and review articles identified by a computerized (MED LINE) and manual (Index Medicus) search. DATA SYNTHESIS: Fluconazole i s a broad-spectrum triazole antifungal agent primarily eliminated by r enal mechanisms, although hepatic cytochrome P-450 inhibition and hepa totoxicity have been observed. We report two cases of fluconazole-indu ced 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 primari ly with high-dose fluconazole and short-term coadministration. CONCLUS IONS: Fluconazole can increase phenytoin serum concentrations leading to toxicity. Constant and continuous monitoring of serum phenytoin con centrations with fluconazole doses as low as 200 mg/d is warranted.