Ticlopidine-induced phenytoin toxicity

OBJECTIVE: To report a probable case of ticlopidine-induced phenytoin toxicity. CASE SUMMARY: A 72-year-old white man suddenly developed combative behavior, refused to leave his room, stopped eating, and began falling to the floor 6 weeks after being given ticlopidine. The total phenytoin concentration was measured at 43.6 mu g/mL; the dosage of phenytoin was decreased and the symptoms later resolved. After ticlopidine was discontinued, the patient was rechallenged with the same dose of phenytoin without symptoms of toxicity. DISCUSSION: Possible mechanisms of the drug interaction are discussed with emphasis on cytochrome P450 metabolism. CONCLUSIONS: Clinicians should be aware of this potentially serious drug interaction and either avoid the phenytoin-ticlopidine combination, or monitor closely for phenytoin toxicity.