Drug interaction between erlotinib and phenytoin for brain metastases in a patient with nonsmall cell lung cancer.

Erlotinib, a substrate drug metabolized by the CYP3A4 enzyme, is an epidermal growth factor receptor tyrosine kinase inhibitor used to treat nonsmall cell lung cancer (NSCLC). Concomitant use of erlotinib and the antiepileptic drug phenytoin, an inducer of CYP3A4, may result in a drug-drug interaction accompanied by changes in the blood concentrations of both drugs. We determined the blood concentration of each drug to confirm the interaction between phenytoin and erlotinib in a case of NSCLC with brain metastases. The phenytoin blood concentration (8.2-10.0µg/mL) gradually increased 3-fold (to 24.2µg/mL) 7 months after the start of erlotinib (150mg/d) co-administration. The erlotinib blood concentration which was maintained at 0.15-0.37µg/mL under phenytoin co-administration, increased 12-fold (to 1.77µg/mL) after the stoppage of phenytoin co-administration. The present case revealed that blood phenytoin increased and blood erlotinib decreased subsequent to the interaction of the 2 drugs in the CYP3A4 metabolic enzyme system.