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

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).

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.

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.