Drug Interactions between atropine / phenobarbital and ribociclib

GENERALLY AVOID: Coadministration with potent CYP450 3A4 inducers may significantly decrease the plasma concentrations and therapeutic effects of ribociclib, which is a substrate of the isoenzyme. In healthy study subjects, administration of a single 600 mg dose of ribociclib with multiple 600 mg daily doses of rifampin, a potent CYP450 3A4 inducer, resulted in an 81% and 89% decrease in ribociclib peak plasma concentration (Cmax) and systemic exposure (AUC), respectively, compared to ribociclib administered alone. In addition, administration of efavirenz, a moderate CYP450 3A4 inducer, is predicted to decrease ribociclib Cmax and AUC by 37% and 60%, respectively. In addition, when two or more medications with similar adverse effect profiles are given concurrently, the likelihood of experiencing these adverse reactions may be increased. For example, coadministration with other agents that can prolong the QT interval (e.g., apalutamide, encorafenib, enzalutamide) may result in additive effects and an increased risk of ventricular arrhythmias like torsade de pointes.

MANAGEMENT: Concomitant use of ribociclib with potent CYP450 3A4 inducers should generally be avoided. Alternative agents with no or minimal CYP450 3A4 induction potential are recommended whenever possible. If coadministration is necessary, dosage adjustments as well as clinical and laboratory monitoring should be considered whenever a potent CYP450 3A4 inducer is added to or withdrawn from therapy. Patients should be monitored for therapeutic failure. If the CYP450 3A4 inducer also carries a risk of prolonging the QT interval, then obtaining more frequent electrocardiograms (ECGs) to monitor the QT interval may be advisable. Patients should be counseled to seek immediate medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, syncope, palpitations, irregular heartbeat, and/or shortness of breath.