Drug Interaction Report

Coadministration with drugs that elevate the gastric pH such as proton pump inhibitors, H2-receptor antagonists, and antacids may decrease the oral bioavailability of ponatinib and reduce its concentrations in plasma. The aqueous solubility of ponatinib has been shown to be pH-dependent, with higher pH resulting in decreased solubility. However, in a drug interaction study in healthy volunteers, coadministration of ponatinib after multiple doses of lansoprazole resulted in a minor reduction in ponatinib Cmax but no change in overall systemic exposure (AUC) compared to ponatinib administered alone. Therefore, ponatinib may be coadministered with medicines that increase gastric pH without dose adjustment or separation of administration.

ADJUST DOSING INTERVAL: Bowel cleansing products can increase the gastrointestinal transit rate. Oral medications administered within one hour of the start of administration of the bowel cleansing solution may be flushed from the gastrointestinal tract and not properly absorbed.

MANAGEMENT: Patients should be advised that absorption of oral medications may be impaired during bowel cleansing treatment. Oral medications (e.g., anticonvulsants, oral contraceptives, antidiabetic agents, antibiotics) should not be administered during and within one hour of starting bowel cleansing treatment whenever possible. However, if concomitant use cannot be avoided, monitoring for reduced therapeutic effects may be advisable.

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.