Drug Interaction Report

MONITOR: Coadministration with CYP450 3A4 inhibitors may increase the plasma concentrations of amlodipine, which is a substrate of the isoenzyme. In 8 elderly hypertensive patients, administration of a single 5 mg dose of amlodipine in combination with the moderate CYP450 3A4 inhibitor diltiazem (180 mg orally daily for 3 days) resulted in a nearly 60% increase in amlodipine peak plasma concentration (Cmax) and systemic exposure (AUC). Associated systolic, diastolic, and standing blood pressures decreased compared to those obtained with amlodipine alone. Erythromycin, another moderate inhibitor, did not significantly alter amlodipine systemic exposure in healthy volunteers. However, pharmacokinetic changes may be more pronounced in elderly patients.

MANAGEMENT: Close monitoring of clinical response and tolerance is recommended if amlodipine is prescribed with potent or moderate CYP450 3A4 inhibitors. Dosage reduction may be required for amlodipine. Patients should be advised to seek medical attention if they experience edema or swelling of the lower extremities; sudden, unexplained weight gain; difficulty breathing; chest pain or tightness; or hypotension as indicated by dizziness, fainting, or orthostasis.

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.