Drug Interaction Report

MONITOR: The risk of peripheral neuropathy may be increased during concurrent use of two or more agents that are associated with this adverse effect. Patient risk factors include diabetes and age older than 60 years. In some cases, the neuropathy may progress or become irreversible despite discontinuation of the medications.

MANAGEMENT: Caution is advised during concomitant use of agents with neurotoxic effects. Patients should be monitored closely for symptoms of neuropathy such as burning, tingling, pain, or numbness in the hands and feet. Since the development of peripheral neuropathy may be dose-related for many drugs, the recommended dosages should generally not be exceeded. Consideration should be given to dosage reduction or immediate discontinuation of these medications in patients who develop peripheral neuropathy to limit further damage. If feasible, therapy should generally be reinstituted only after resolution of neuropathy symptoms or return of symptoms to baseline status. In some cases, permanent dosage reductions may be required.

GENERALLY AVOID: Coadministration with grapefruit juice is likely to increase the plasma concentrations of ponatinib, which is primarily metabolized by CYP450 3A4. However, the interaction has not been studied. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: The consumption of grapefruit, grapefruit juice, and supplements that contain grapefruit extract should be avoided during treatment with ponatinib.