Drug Interactions between darunavir and talazoparib

MONITOR: Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the plasma concentrations of talazoparib, which has been shown in vitro to be a substrate of the efflux transporter. In a drug-drug interaction study in patients with advanced solid tumors, compared with a single talazoparib dose (0.5 mg), multiple daily doses of the P-gp inhibitor itraconazole (100 mg twice daily) with a single dose of talazoparib (0.5 mg) increased the talazoparib total exposure and peak plasma concentration by 56% and 40%, respectively. In addition, population pharmacokinetic analysis has shown that 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%.

MANAGEMENT: No initial dosage adjustment is recommended by the manufacturer when talazoparib is coadministered with inhibitors of 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.