Giotrif Drug Interactions

Interactions with drug transport systems: Effects of P-gp and breast cancer resistance protein (BCRP) inhibitors on afatinib: In vitro studies have demonstrated that afatinib is a substrate of P-gp and BCRP. When the strong P-gp and BCRP inhibitor ritonavir (200 mg twice a day for 3 days) was administered 1 hour before a single dose of 20 mg GIOTRIF, exposure to afatinib increased by 48% (area under the curve (AUC_0-∞)) and 39% (maximum plasma concentration (C_max)). In contrast, when ritonavir was administered simultaneously or 6 hours after 40 mg GIOTRIF, the relative bioavailability of afatinib was 119% (AUC_0-∞) and 104% (C_max) and 111% (AUC_0-∞) and 105% (C_max), respectively. Therefore, it is recommended to administer strong P-gp inhibitors (including but not limited to ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone) using staggered dosing, preferably 6 hours or 12 hours apart from GIOTRIF (see Dosage & Administration).
Effects of P-gp inducers on afatinib: Pre-treatment with rifampicin (600 mg once daily for 7 days), a potent inducer of P-gp, decreased the plasma exposure to afatinib by 34% (AUC_0-∞) and 22% (C_max) after administration of a single dose of 40 mg GIOTRIF. Strong P-gp inducers (including but not limited to rifampicin, carbamazepine, phenytoin, phenobarbital or St. John's wort (Hypericum perforatum)) may decrease exposure to afatinib (see Precautions).
Effects of afatinib on P-gp substrates: Based on in vitro data, afatinib is a moderate inhibitor of P-gp. However, based on clinical data it is considered unlikely that GIOTRIF treatment will result in changes of the plasma concentrations of other P-gp substrates.
Interactions with BCRP: In vitro studies indicated that afatinib is a substrate and an inhibitor of the transporter BCRP. Afatinib may increase the bioavailability of orally administered BCRP substrates (including but not limited to rosuvastatin and sulfasalazine).
Food effect on afatinib: Co-administration of a high-fat meal with GIOTRIF resulted in a significant decrease of exposure to afatinib by about 50% in regard to C_max and 39% in regard to AUC_0-∞. This medicinal product should be administered without food (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).