Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 3A4 and/or P-glycoprotein (P-gp) may increase the plasma concentrations of apixaban, which is a substrate of both the isoenzyme and efflux transporter. When apixaban was coadministered with the moderate CYP450 3A4 and P-gp inhibitor diltiazem (360 mg once a day), mean apixaban peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.3- and 1.4-fold, respectively. Likewise, coadministration with the P-gp inhibitor naproxen (500 mg single dose) increased the mean apixaban Cmax and AUC by approximately 1.6- and 1.5-fold, respectively.

MANAGEMENT: No dosage adjustment for apixaban is required during concomitant therapy with lone inhibitors of CYP450 3A4 or P-gp, or moderate or weak dual inhibitors of both CYP450 3A4 and P-gp. However, caution may be advisable. Closer monitoring of the pharmacologic effects of apixaban may be appropriate whenever a CYP450 3A4 or P-gp inhibitor is added to or withdrawn from therapy. Patients should be routinely evaluated for signs and symptoms suggesting blood loss such as a drop in hemoglobin and/or hematocrit, hypotension, or fetal distress (in pregnant women).

GENERALLY AVOID: Pomegranates and grapefruit may increase the systemic exposure to ribociclib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in these fruits. Increased exposure to ribociclib may increase the risk of adverse effects such as infections, neutropenia, leukopenia, anemia, thrombocytopenia, anorexia, nausea, vomiting, diarrhea, stomatitis, alopecia, fatigue, headache, and abnormal liver function may be increased.

MANAGEMENT: Patients receiving ribociclib should avoid consumption of pomegranates or pomegranate juice and grapefruit or grapefruit juice during treatment.