What are the precautions for Revuforj (Revumenib)?

In the clinical study of Revuforj (Revumenib) in the treatment of acute leukemia, differentiation syndrome, QTc interval prolongation, embryo-fetal toxicity and other warnings and precautions appeared. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity.

1. Differentiation syndrome (DS): Revuforj can cause fatal or life-threatening DS. Symptoms of differentiation syndrome, including symptoms in patients treated with Revuforj, include fever, dyspnea, hypoxia, peripheral edema, pleuropericardial effusion, acute renal failure, and/or hypotension.

Before starting treatment with Revuforj, reduce the white blood cell count (WBC) to less than 25 micrograms per liter (Gi/L). If DS is suspected, initiate systemic corticosteroid therapy immediately (eg, dexamethasone 10 mg intravenously every 12 hours in adults or dexamethasone 0.25 mg/kg/dose intravenously every 12 hours in children weighing less than 40 kg) and continue for at least 3 days until signs and symptoms resolve. Supportive measures and hemodynamic monitoring were instituted until improvement. Interrupt Revuforj if severe signs and/or symptoms persist for more than 48 hours after initiating systemic corticosteroid therapy, or if life-threatening symptoms develop (e.g., pulmonary symptoms requiring ventilator support). If DS relapses after tapering corticosteroids, steroids should be restarted immediately.

2. QTc interval prolongation: Revuforj can cause QT (QTc) interval prolongation. Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, before treatment with Revuforj. Perform an ECG before initiating Revuforj therapy and do not initiate Revuforj therapy in patients with QTcF >450 msec. Perform an EKG at least once a week during the first 4 weeks of treatment and at least once a month thereafter. More frequent ECG monitoring may be needed in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or who are taking drugs known to prolong the QTc interval. Coadministration of Revuforj with drugs known to prolong the QTc interval may increase the risk of QTc interval prolongation.

If QTcF increases to >480 msec and <500msec, interrupt Revuforj and restart Revuforj at the same dose twice daily after the QTcF interval returns to ≤480 msec. Interrupt Revuforj if QTcF increases to >500 msec or increases >60 msec from baseline and restart Revuforj twice daily at a lower dose level after the QTcF interval returns to ≤480 msec. Revuforj should be permanently discontinued in patients with ventricular arrhythmias and in patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmias.

3. Embryo- Fetal toxicity: Based on animal test results and its mechanism of action, Revuforj taken by pregnant women can cause harm to the fetus. In an animal reproduction study, oral administration of revumenib to pregnant rats during organogenesis resulted in adverse developmental outcomes, including embryo-fetal death, malformations, and altered fetal growth, with maternal exposures approximately 0.5 times the human exposure (AUC) at the recommended dose.

Inform pregnant women of potential risks to the fetus. Advise females of reproductive potential and males who are partners of a female of reproductive potential to use an effective method of contraception during treatment with Revuforj and for 4 months after the last dose.

Reference materials:https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6eb3cdbc-0e74-477d-82d6-3bb172d3f63f