Drug Interactions between Kisqali Femara Co-Pack and levamlodipine

MONITOR: Coadministration with ribociclib may increase the plasma concentrations and pharmacologic effects of drugs that are substrates of CYP450 3A4. The proposed mechanism is decreased clearance due to ribociclib-mediated inhibition of CYP450 3A4 metabolism. In healthy study subjects, administration of midazolam, a sensitive CYP450 3A4 substrate, with multiple 400 mg daily doses of ribociclib increased the midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) by 2.1-fold and 3.8-fold, respectively, compared to midazolam administered alone. When given at a clinically relevant dose of 600 mg daily, ribociclib is predicted to increase midazolam Cmax and AUC by 2.4-fold and 5.2-fold, respectively.

MANAGEMENT: Caution is advised when ribociclib is used concomitantly with drugs that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ribociclib is added to or withdrawn from therapy.

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.