Drug Interactions between ponatinib and rifabutin

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of ponatinib. In vitro, ponatinib has been shown to undergo Phase I metabolism primarily via CYP450 3A4 and to a lesser extent, CYP450 2C8, 2D6 and 3A5. When a single 45 mg dose of ponatinib was administered to healthy subjects following 7 days of continuous daily dosing of 600 mg rifampin, a potent CYP450 3A4 inducer, mean ponatinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 42% and 62%, respectively, compared to ponatinib administered alone. Similar results were observed with thrice daily administration of 100 mg oral phenytoin, another potent CYP450 3A4 inducer, using physiologically based pharmacokinetic modeling. Loss of therapeutic effect may occur.

MANAGEMENT: Concomitant use of ponatinib with potent CYP450 3A4 inducers should generally be avoided. Alternative agents with no or minimal CYP450 3A4 induction potential are recommended whenever possible. Patients should be monitored for reduced efficacy of ponatinib if use of potent CYP450 3A4 inducers is required.