Drug Interactions between donepezil and phenobarbital

MONITOR: Coadministration with drugs that are inducers of the CYP450 3A4 and/or 2D6 enzymatic pathways may decrease the plasma concentrations of donepezil. The mechanism is accelerated clearance of donepezil due to enhanced CYP450 activities. 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: While clinical data are lacking, the possibility of a diminished therapeutic response to donepezil should be considered in patients receiving concomitant inducer agents. 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. The prescribing information for the concomitant CYP450 3A4 inducers should be consulted for specific recommendations.

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