Interactions : אינטראקציות

4.5    Interaction with other medicinal products and other forms of interaction

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 (AUC0-∞)) and 39%
(maximum plasma concentration (Cmax)). In contrast, when ritonavir was administered simultaneously or 6 hours after 40 mg GIOTRIF, the relative bioavailability of afatinib was 119% (AUC0-∞) and 104% (Cmax) and 111% (AUC0-∞) and 105% (Cmax), 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 section 4.2).

Giotrif                                                                            Updated Prescribing Information Film coated tablets 20mg, 30mg, 40mg, 50mg                                                         December 2019 

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% (AUC0-∞) and 22% (Cmax) 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 section 4.4).

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 Cmax and 39% in regard to AUC0-∞. This medicinal product should be administered without food (see sections 4.2 and 5.2).