Drug Interaction Report

ADJUST DOSING INTERVAL: Products containing aluminum, calcium, magnesium and other polyvalent cations such as antacids or vitamin with mineral supplements are likely to interfere with the gastrointestinal absorption of oral bisphosphonates. For example, the bioavailability of tiludronate has been shown to decrease 80% during simultaneous administration with calcium, and 60% when aluminum- or magnesium-containing antacids were administered one hour before tiludronate.

MANAGEMENT: Antacids or other oral medications containing aluminum, calcium, magnesium and other polyvalent cations should be administered at least 30 minutes after the bisphosphonate dose.

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: Administration with food may increase the absorption of calcium. However, foods high in oxalic acid (spinach or rhubarb), or phytic acid (bran and whole grains) may decrease calcium absorption.

MANAGEMENT: Calcium may be administered with food to increase absorption. Consider withholding calcium administration for at least 2 hours before or after consuming foods high in oxalic acid or phytic acid.

ADJUST DOSING INTERVAL: Food significantly decreases the bioavailability of risedronate, possibly to negligible levels.

MANAGEMENT: Risedronate should be administered with 180 to 240 mL (6 to 8 ounces) of plain water, at least 30 minutes before the first food, beverage, or medication of the day. Patients should remain upright for at least 30 minutes following administration of risedronate.

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.