Drug Interaction Between Erlotinib and Itraconazole in a Patient With Non–Small Cell Lung Cancer

Introduction Erlotinib (ERL) is metabolized primarily by cytochrome P450 (CYP) 3A4. We report a case of non–small cell lung cancer in which plasma ERL concentrations increased following coadministration of itraconazole (ITCZ). Case Presentation In this patient, a 67‐year‐old man receiving ERL 150 mg/day, the trough plasma concentration ( C 0 ) of ERL and its major metabolite, O‐desmethyl ERL (OSI‐420), increased following coadministration of ITCZ. The total clearance of ERL at steady state was 6.1 L/h. The mean C 0 of ERL and OSI‐420 were 437 and 47.1 ng/mL, respectively, and the C 0 ratio of OSI‐420/ERL was 0.108. With coadministration of oral ITCZ (200 mg/day capsule), the mean C 0 of ERL and OSI‐420 increased to 1124 and 166 ng/mL, respectively, and the mean C 0 ratio of OSI‐420/ERL increased to 0.147. The mean C 0 of ITCZ and the sum of ITCZ and the active metabolite hydroxyitraconazole (OH‐ITCZ) were 109 and 271 ng/mL, respectively. The mean C 0 of ERL increased approximately 2.5‐fold. Conclusion Even at the relatively lower C 0 of ITCZ (compared with the recommended target value), ITCZ coadministration increased the C 0 of ERL. In patients with a sufficient ERL C 0 of more than 500 ng/mL prior to ITCZ coadministration or patients exhibiting adequate absorption of oral ITCZ, the risk of ERL‐related adverse events with ITCZ coadministration may increase due to further elevation of the ERL C 0 . Therefore, when ERL is coadministered with ITCZ, careful monitoring for adverse effects and appropriate dose adjustments are required, considering potential changes in ERL concentrations. Management using the C 0 of ERL and ITCZ may be necessary.