Drug Interaction Report

MONITOR: Coadministration with ruxolitinib may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein efflux transporter and/or the breast cancer resistance protein (BRCP) in the intestine. The mechanism is decreased clearance via these routes due to inhibition by ruxolitinib. The clinical significance is unknown.

MANAGEMENT: Caution is advised if ruxolitinib must be used concurrently with medications that are substrates of the P-glycoprotein efflux transporter and/or the breast cancer resistance protein (BRCP) , particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ruxolitinib is added to or withdrawn from therapy. The interaction may possibly be avoided or minimized if the doses of the affected medications are separated for as long as possible.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ruxolitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients treated with ruxolitinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Ruxolitinib may be administered with or without food.

Administration of digoxin with a high-fiber meal has been shown to decrease its bioavailability by almost 20%. Fiber can sequester up to 45% of the drug when given orally. Patients should be advised to maintain a regular diet without significant fluctuation in fiber intake while digoxin is being titrated.

Grapefruit juice may modestly increase the plasma concentrations of digoxin. The mechanism is increased absorption of digoxin due to mild inhibition of intestinal P-glycoprotein by certain compounds present in grapefruits. In 12 healthy volunteers, administration of grapefruit juice with and 30 minutes before, as well as 3.5, 7.5, and 11.5 hours after a single digoxin dose (0.5 mg) increased the mean area under the plasma concentration-time curve (AUC) of digoxin by just 9% compared to administration with water. Moreover, P-glycoprotein genetic polymorphism does not appear to influence the magnitude of the effects of grapefruit juice on digoxin. Thus, the interaction is unlikely to be of clinical significance.