Koselugo Drug Interactions

Pharmacokinetic interactions: Interaction studies have only been performed in healthy adults (aged ≥18 years).
Active substances that may increase selumetinib plasma concentrations: Co-administration with a strong CYP3A4 inhibitor (200 mg itraconazole twice daily for 4 days) increased selumetinib C_max by 19% (90% CI 4, 35) and AUC by 49% (90% CI 40, 59) in healthy adult volunteers. Concomitant use of erythromycin (moderate CYP3A4 inhibitor) is predicted to increase selumetinib AUC by 41% and C_max by 23%.
Co-administration with a strong CYP2C19/moderate CYP3A4 inhibitor (200 mg fluconazole once daily for 4 days) increased selumetinib C_max by 26% (90% CI 10, 43) and AUC by 53% (90% CI 44, 63) in healthy adult volunteers, respectively.
Concomitant use of erythromycin (moderate CYP3A4 inhibitor) or fluoxetine (strong CYP2C19/CYP2D6 inhibitor) is predicted to increase selumetinib AUC by ~30-40% and C_max by ~20%.
Co-administration with medicinal products that are strong inhibitors of CYP3A4 (e.g., clarithromycin, grapefruit juice, oral ketoconazole) or CYP2C19 (e.g., ticlopidine) should be avoided. Co-administration with medicinal products that are moderate inhibitors of CYP3A4 (e.g., erythromycin and fluconazole) or CYP2C19 (e.g., omeprazole) should be avoided. If co-administration is unavoidable, patients should be carefully monitored for adverse events and the selumetinib dose should be reduced (see Dosage & Administration and Table 6).
Active substances that may decrease selumetinib plasma concentrations: Co-administration with a strong CYP3A4 inducer (600 mg rifampicin daily for 8 days) decreased selumetinib C_max by -26% (90% CI -17, -34) and AUC by -51% (90% CI -47, -54).
Concomitant use of efavirenz (moderate CYP3A4 inducer) is predicted to decrease selumetinib AUC by -38% and C_max by -22%. Avoid concomitant use of strong CYP3A4 inducers (e.g., phenytoin, rifampicin, carbamazepine, St. John's Wort) or moderate CYP3A4 inducers with KOSELUGO.
Active substances whose plasma concentrations may be altered by selumetinib: In vitro, selumetinib is an inhibitor of OAT3 and the potential for a clinically relevant effect on the pharmacokinetics of concomitantly administered substrates of OAT3 cannot be excluded (see Pharmacology: Pharmacodynamics under Actions).
Vitamin E: KOSELUGO capsules contain vitamin E as the excipient TPGS. Therefore, patients should avoid taking supplemental vitamin E and anticoagulant assessments should be performed more frequently in patients taking concomitant anticoagulant or antiplatelet medications (see Precautions).