Phenytoin decreases the levels of
voriconazole and
posaconazole by about 50%. Also,
voriconazole increases the maximum
serum levels and AUC of
phenytoin by 67% and 81%, respectively. Potentially clinically significant increases in
phenytoin levels have been reported in some patients taking
posaconazole. Fosphenytoin, a prodrug of
phenytoin, may interact similarly.
Concurrent use should be avoided unless the benefits outweigh the risks. If both drugs are used be alert for evidence of
phenytoin toxicity (blurred vision,
nystagmus, ataxia or drowsiness) and, if necessary, adjust the dose based on
phenytoin levels. The dose of oral
voriconazole should be increased from 200 to 400 mg twice daily, or from 100 mg to 200 mg twice daily in patients who weigh less than 40 kg, and
intravenous voriconazole should be increased from 4 to 5 mg/kg twice daily. Similarly, consideration should be given to increasing the
posaconazole dose.