Drug Interactions between alpelisib and talazoparib

MONITOR: Coadministration with inhibitors of P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP) may increase the plasma concentrations of talazoparib, which has been shown in vitro to be a substrate of both efflux membrane transporters. In clinical studies, administration of talazoparib with the P-gp inhibitors amiodarone, carvedilol, clarithromycin, itraconazole, and verapamil resulted in an approximate 45% increase in talazoparib exposure and an increase in the rate of talazoparib dose reduction. In contrast, coadministration with the P-gp inhibitors azithromycin, atorvastatin, diltiazem, felodipine, fluvoxamine, and quercetin increased talazoparib exposure by just 8%. The effect of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied.

MANAGEMENT: No initial dosage adjustment is recommended by the manufacturer when talazoparib is coadministered with inhibitors of BCRP and/or P-gp other than amiodarone, carvedilol, clarithromycin, itraconazole, or verapamil. However, patients should be closely monitored for adverse effects such as myelosuppression and myelodysplastic syndrome/acute myeloid leukemia, and dosage adjustments made or treatment withheld as needed in accordance with the product labeling.