Drug Interactions between revumenib and Tuinal

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of revumenib and increase plasma concentrations of its active metabolite M1, as revumenib has been shown to be primarily metabolized by the isoenzyme. Reduced therapeutic efficacy of revumenib and an increased risk of QT interval prolongation due to increased systemic exposures of M1 may occur. However, pharmacokinetic and clinical data from drug interaction studies are unavailable.

MANAGEMENT: The potential for diminished pharmacologic effects of revumenib and an increased risk of QT interval prolongation should be considered during coadministration with CYP450 3A4 inducers. Pharmacologic response to revumenib should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy. It is advised to perform an electrocardiogram (ECG) prior to the initiation of revumenib, at least once a week for the first 4 weeks, and at least monthly thereafter to monitor for QT prolongation. Revumenib should not be started if baseline QTc is greater than 450 msec. Likewise, treatment should be interrupted and adjusted in accordance with the product labeling in patients who develop QTc prolongation greater than 480 msec. 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.

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of revumenib and increase plasma concentrations of its active metabolite M1, as revumenib has been shown to be primarily metabolized by the isoenzyme. Reduced therapeutic efficacy of revumenib and an increased risk of QT interval prolongation due to increased systemic exposures of M1 may occur. However, pharmacokinetic and clinical data from drug interaction studies are unavailable.

MANAGEMENT: The potential for diminished pharmacologic effects of revumenib and an increased risk of QT interval prolongation should be considered during coadministration with CYP450 3A4 inducers. Pharmacologic response to revumenib should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy. It is advised to perform an electrocardiogram (ECG) prior to the initiation of revumenib, at least once a week for the first 4 weeks, and at least monthly thereafter to monitor for QT prolongation. Revumenib should not be started if baseline QTc is greater than 450 msec. Likewise, treatment should be interrupted and adjusted in accordance with the product labeling in patients who develop QTc prolongation greater than 480 msec. 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.