Drug Interactions between Meprozine and revumenib

GENERALLY AVOID: Revumenib causes dose-related prolongation of the QT interval. Coadministration with other agents that can prolong the QT interval may result in additive effects and an increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In clinical trials, QT interval prolongation was reported as an adverse reaction in 29% of patients treated with revumenib at the recommended dosage for relapsed or refractory acute leukemia with a KMT2A translocation. Additionally, Grade 3 QT interval prolongation occurred in 12% of those patients and a greater than 60 msec increase in Fridericia-corrected QT interval (QTcF) from baseline was reported in 18% of patients. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypocalcemia). Moreover, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: It is recommended to avoid revumenib in combination with other drugs that can prolong the QT interval. If concomitant use cannot be avoided, obtain electrocardiograms (ECGs) when initiating, during concomitant use, and as clinically indicated. Serum electrolytes, including potassium, magnesium, and calcium, should be monitored before starting revumenib therapy and monthly during treatment. 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 advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. Permanently discontinue revumenib in patients who develop QTc interval prolongation with life-threatening arrhythmia.

ADJUST DOSE: The central nervous system and respiratory depressant effects of meperidine may be potentiated by concomitant use of other agents with CNS depressant effects. An increased risk of serious adverse reactions such as respiratory depression, hypotension, profound sedation, syncope, coma, and even death should be considered, particularly in elderly or debilitated patients.

MANAGEMENT: Caution and dosage adjustments are advisable when meperidine is used in combination with other narcotic analgesics, general anesthetics, phenothiazines, sedative-hypnotics, tranquilizers, tricyclic antidepressants, or other CNS depressants such as alcohol. A lower dosage of meperidine should be considered initially, then titrated carefully according to pain level and clinical response. Meperidine dosage reductions of 25% to 50% have been recommended for patients receiving phenothiazines and other tranquilizers. Patients should be advised to avoid rising abruptly from a sitting or recumbent position, and to notify their physician if they experience dizziness, lightheadedness, orthostasis, syncope, tachycardia, or excessive CNS effects that interfere with their normal activities. Patients should also avoid driving or operating hazardous machinery until they know how these medications affect them.