Xospata Drug Interactions

Gilteritinib is primarily metabolised by CYP3A enzymes, which can be induced or inhibited by a number of concomitant medicinal products.
Effects of other medicinal products on Xospata: CYP3A/P-gp Inducers: Concomitant use of Xospata with strong CYP3A/P-gp inducers (e.g., phenytoin, rifampin and St. John's Wort) should be avoided because they can decrease gilteritinib plasma concentrations. In healthy subjects, co-administration of rifampicin (600 mg), a strong CYP3A/P-gp inducer, to steady state with a single 20 mg dose of gilteritinib decreased gilteritinib mean C_max by 27% and mean AUC_inf by 70%, respectively, compared to subjects administered a single dose of gilteritinib alone (see Precautions).
CYP3A, P-gp and/or BCRP inhibitors: Strong inhibitors of CYP3A, P-gp and/or BCRP (e.g., voriconazole, itraconazole, posaconazole, clarithromycin, erythromycin, captopril, carvedilol, ritonavir, azithromycin) can increase gilteritinib plasma concentrations. A single, 10 mg dose of gilteritinib co-administered with itraconazole (200 mg once daily for 28 days), a strong CYP3A, P-gp and BCRP inhibitor, to healthy subjects resulted in an approximate 20% increase in mean C_max and 2.2-fold increase in mean AUC_inf relative to subjects administered a single dose of gilteritinib alone. Gilteritinib exposure increased approximately 1.5-fold in patients with relapsed or refractory AML when co-administered with a strong CYP3A, P-gp and/or BCRP inhibitor (see Precautions).
Effects of Xospata on other medicinal products: Gilteritinib as an inhibitor or inducer: Gilteritinib is not an inhibitor or inducer of CYP3A4 or an inhibitor of MATE1 in vivo. The pharmacokinetics of midazolam (a sensitive CYP3A4 substrate) were not significantly (C_max and AUC increased approximately 10%) affected after once-daily administration of gilteritinib (300 mg) for 15 days in patients with FLT3-mutated relapsed or refractory AML. Additionally, the pharmacokinetics of cephalexin (a sensitive MATE1 substrate) were not significantly (C_max and AUC decreased by less than 10%) affected after once daily administration of gilteritinib (200 mg) for 15 days in patients with FLT3-mutated relapsed or refractory AML.
Gilteritinib is an inhibitor of P-gp, BCRP and OCT1 in vitro. As no clinical data is available, it cannot be excluded that gilteritinib could inhibit these transporters at a therapeutic dose. Caution is advised during co-administration of gilteritinib with substrates of P-gp (e.g., digoxin, dabigatran etexilate), BCRP (e.g., mitoxantrone, methotrexate, rosuvastatin) and OCT1 (e.g., metformin).
5HT_2B receptor or sigma nonspecific receptor: Based on in vitro data, gilteritinib may reduce the effects of medicinal products that target 5HT_2B receptor or sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline). Avoid concomitant use of these medicinal products with Xospata unless use is considered essential for the care of the patient.