Drug Interactions between ivacaftor / lumacaftor and vonoprazan

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of vonoprazan, which is metabolized by the isoenzyme. When coadministered with potent CYP450 3A4 inducers, vonoprazan systemic exposure (AUC) is predicted to decrease by 80%. Reduced efficacy of vonoprazan may occur.

MANAGEMENT: According to the manufacturer, concomitant use of vonoprazan with potent CYP450 3A4 inducers should be avoided.

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of ivacaftor, which is primarily metabolized by the isoenzyme. The interaction occurs to a greater extent when ivacaftor is administered as monotherapy than when administered in combination with lumacaftor, a potent CYP450 3A4 inducer. In study subjects, ivacaftor systemic exposure (AUC) increased by 8.5-fold when it was administered concomitantly with the potent CYP450 3A4 inhibitor ketoconazole and by 3-fold with the moderate CYP450 3A4 inhibitor fluconazole. By contrast, when lumacaftor/ivacaftor was coadministered with the potent CYP450 3A4 inhibitor itraconazole, ivacaftor peak plasma concentration (Cmax) and AUC increased by an average of 3.7- and 4.3-fold, respectively, and when coadministered with the moderate CYP450 3A4 inhibitor ciprofloxacin, ivacaftor Cmax and AUC increased by just 29% each.

MANAGEMENT: Caution is advised if ivacaftor is used with CYP450 3A4 inhibitors. A dosage adjustment for ivacaftor may be required if undue adverse effects occur.