Drug Interactions between Grafapex and ripretinib

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of ripretinib and its active metabolite, DP-5439. Both ripretinib and DP-5439 are primarily metabolized by CYP450 3A4, with minor contribution from CYP450 2C8 and 2D6. DP-5439 is also a substrate for the P-glycoprotein and breast cancer resistance protein (BCRP) efflux transporters in vitro. When a single 50 mg dose of ripretinib was administered in 20 healthy volunteers treated with 200 mg once daily itraconazole, a potent CYP450 3A4 and P-gp inhibitor, ripretinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 36% and 99%, respectively, while the Cmax and AUC of DP-5439 increased by 6% and 99%, respectively, compared to administration of ripretinib alone. The extent to which other, less potent inhibitors of CYP450 3A4 may interact with ripretinib and its metabolite is unknown.

MANAGEMENT: Caution is advised when ripretinib is used concomitantly with CYP450 3A4 inhibitors. Patients should be monitored more frequently for ripretinib-related toxicities such as palmar-plantar erythrodysesthesia, hypertension, cardiac dysfunction and arthralgia/myalgia, and the treatment discontinued or dosing withheld or adjusted in accordance with the product labeling as necessary.