Important drug interaction involving phenytoin and quetiapine

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.

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.

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.