Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 1A2 and/or 3A4 may increase the plasma concentrations of levobupivacaine, which is primarily metabolized by these isoenzymes. Although no clinical studies have been conducted, the possibility of prolonged and/or increased pharmacologic effects of levobupivacaine should be considered.

MANAGEMENT: Caution may be advisable if levobupivacaine is administered to patients receiving inhibitors of CYP450 1A2 (e.g., quinolones, deferasirox, mexiletine, propafenone, ticlopidine, zileuton) or CYP450 3A4 (e.g., azole antifungals, macrolide antibiotics, protease inhibitors, kinase inhibitors, aprepitant, conivaptan, cyclosporine, delavirdine, diltiazem, nefazodone, verapamil). Particular caution and dosage adjustment of levobupivacaine may be warranted during concomitant use of both a CYP450 1A2 inhibitor and a CYP450 3A4 inhibitor, or a drug that inhibits both isoenzymes (e.g., fluvoxamine). Patients should be monitored for early signs and symptoms of central nervous system toxicity such as dizziness, drowsiness, lightheadedness, anxiety, restlessness, incoherent speech, tremors, twitching, numbness and tingling of the mouth and lips, metallic taste, tinnitus, and blurred vision, as well as more serious reactions including convulsions, hypotension, arrhythmias, and cardiorespiratory depression.

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.