Important drug interaction involving phenytoin and quetiapine

OBJECTIVE: To describe a patient case in which a drug interaction involving quetiapine and phenytoin resulted in an absence of clinical response and serum quetiapine levels below the point of detection. CASE SUMMARY: This patient was on concurrent phenytoin, valproic acid, and quetiapine therapy for 10 months. Prior to discontinuing phenytoin, a serum quetiapine level was found to be less than 10 ng/mL. It took approximately 1 month after phenytoin's discontinuation for quetiapine levels to attain measurable concentrations. The patient's clinical response to quetiapine improved significantly after this interaction resolved. DISCUSSION: Phenytoin is an inducer of cytochrome P450 3A4, and quetiapine is a substrate of this enzyme. Patients on concurrent phenytoin and quetiapine therapy may require monitoring of quetiapine concentrations, which is often not routine practice, as this drug interaction can result in a clinically significant reduction in quetiapine levels contributing to a lack of efficacy.