Revumenib
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: DIFFERENTIATION SYNDROME, QTc PROLONGATION and TORSADES DE POINTES Differentiation syndrome, which can be fatal, has occurred with REVUFORJ. Signs and symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and renal dysfunction. If differentiation syndrome is suspected, immediately initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution. [see Dosage and Administration (2.3 ) , Warnings and Precautions (5.1) , and Adverse Reactions (6.1) ] . QTc prolongation and Torsades de Pointes have occurred in patients receiving REVUFORJ.
Correct hypokalemia and hypomagnesemia prior to and during treatment. Do not initiate REVUFORJ in patients with QTcF > 450 msec. If QTc interval prolongation occurs, interrupt, reduce, or permanently discontinue REVUFORJ. [see Dosage and Administration (2.3) , Warnings and Precautions (5.2) , and Adverse Reactions (6.1) ] WARNING: DIFFERENTIATION SYNDROME, and QTc PROLONGATION and TORSADES DE POINTES See full prescribing information for complete boxed warning. Differentiation syndrome, which can be fatal, has occurred with REVUFORJ.
If differentiation syndrome is suspected, immediately initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution ( 2.3 , 5.1 ) QTc prolongation and Torsades de Pointes have occurred in patients receiving REVUFORJ. Correct hypokalemia and hypomagnesemia prior to and during treatment. Do not initiate REVUFORJ in patients with QTcF > 450 msec. If QTc interval prolongation occurs, interrupt, reduce, or permanently discontinue REVUFORJ. ( 2.3 , 5.2 ).
Dosing in kidney impairment
Symptoms of differentiation syndrome, including those seen in patients treated with REVUFORJ, include fever, dyspnea, hypoxia, peripheral edema, pleuropericardial effusion, acute renal failure, rash, and/or hypotension. In clinical trials, DS occurred in 60 (25%) of 241 patients treated with REVUFORJ at the recommended dosage for relapsed or refractory acute leukemia [see Adverse Reactions ] .
Dosing in liver impairment
Dosage Modifications for Adverse Reactions Assess blood counts, electrolytes, and liver enzymes prior to the initiation of REVUFORJ and monthly thereafter. Perform an electrocardiogram (ECG) prior to the initiation of REVUFORJ, at least once a week for the first 4 weeks, and at least monthly thereafter. Monitor for QTc interval prolongation and manage any abnormalities promptly [see Warnings and Precautions and Adverse Reactions ] .
Interrupt dosing or reduce dose for adverse reactions as per Table 3. Dose levels for dose reductions are listed in Table 4, Table 5, and Table 6. [See table below.] Potassium 3.6-3.9 mEq/L, and/or Magnesium 1.7-1.9 mg/dL or 0.66-0.81 mmol/L Supplement potassium and/or magnesium. Continue REVUFORJ. Potassium ≤ 3.5 mEq/L, and/or Magnesium ≤ 1.6 mg/dL or ≤ 0.65 mmol/L Supplement potassium and/or magnesium, and recheck levels within 24 hours.
On recheck of potassium and magnesium labs within 24 hours, if potassium is greater than 3.5 mEq/L and/or magnesium is greater than 1.6 mg/dL, continue REVUFORJ. If potassium is less than 3.5 mEq/L and/or magnesium is less than 1.6 mg/dL, hold REVUFORJ and continue supplementation; resume REVUFORJ at the same dose level when the correction is complete.
Other nonhematological adverse reactions Grade ≥ 3* [see Adverse Reactions ] Interrupt REVUFORJ until recovery to Grade 1* or baseline. If recovered in ≤ 7 days, restart REVUFORJ at the same dose level. If the same Grade ≥ 3* toxicity recurs, interrupt REVUFORJ until recovery to Grade 1* or baseline. Restart REVUFORJ at the reduced dose level.** If recovered in > 7 days, restart REVUFORJ at the reduced dose level.** If the same Grade ≥ 3* toxicity recurs, discontinue REVUFORJ.
Grade 4* neutropenia or thrombocytopenia [see Adverse Reactions ] Interrupt REVUFORJ until recovery to Grade ≤ 2* or baseline. Restart REVUFORJ at the same dose level. If Grade 4* neutropenia or thrombocytopenia recurs without attributable cause, interrupt REVUFORJ until recovery to Grade ≤ 3*. Restart REVUFORJ at the reduced dose level.** Grade 3* or higher allergic reactions [see Adverse Reactions ] Permanently discontinue REVUFORJ. [See table below.] [See table below.] [See table below.] 0.5 50 mg twice daily 25 mg twice daily 0.4 25 mg twice daily 25 mg twice daily
Drug interactions
Check revumenib against a medication listLabel text (4 paragraphs)
Strong CYP3A4 Inhibitors: Reduce the REVUFORJ dose. ( 2.2 , 7.1 ) Strong or moderate CYP3A4 Inducers: Avoid concomitant use with REVUFORJ. ( 7.1 ) QTc Prolonging Drugs: Avoid concomitant use with REVUFORJ. If concomitant use is unavoidable, monitor patients more frequently for QTc interval prolongation. ( 5.2 , 7.1 )
7.1 Effect of Other Drugs on REVUFORJ Strong CYP3A4 Inhibitors If concomitant use of strong CYP3A4 inhibitors is required, reduce the REVUFORJ dosage [see Recommended Dosage (2.2) ] . Revumenib is primarily metabolized by CYP3A4 [see Clinical Pharmacology (12.3) ] . Concomitant use with a strong CYP3A4 inhibitor increases revumenib systemic exposure [see Clinical Pharmacology(12.3) ] , which may increase the risk of REVUFORJ adverse reactions. Strong or Moderate CYP3A4 Inducers Avoid concomitant use with strong or moderate CYP3A4 inducers. Revumenib is primarily metabolized by CYP3A4 [see Clinical Pharmacology (12.3) ] .
Concomitant use with a strong or moderate CYP3A4 inducer may decrease revumenib and increase M1 systemic exposure [see Clinical Pharmacology (12.3) ] , which may reduce REVUFORJ efficacy or increase the risk of QT prolongation associated with the M1 metabolite. Drugs that Prolong QTc Interval Avoid concomitant use of REVUFORJ with other drugs with a known potential to prolong QTc interval. If concomitant use cannot be avoided, obtain ECGs when initiating, during concomitant use, and as clinically indicated [see Warnings and Precautions (5.2) ] . Withhold REVUFORJ if the QTc interval is greater than 480 msec.
Restart REVUFORJ after the QTc interval returns to less than or equal to 480 msec [see Dosage and Administration (2.3) ] . REVUFORJ causes QTc interval prolongation [see Clinical Pharmacology (12.2) ] . Concomitant use of REVUFORJ with other drugs that prolong QTc interval may result in an increase in the QTc interval and adverse reactions associated with QTc interval prolongation [see Warnings and Precautions(5.2) ].
Contraindications
None. None. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
E*Likelihood score E*: Unproven but suspected rare cause of clinically apparent liver injury.
Revumenib is a small molecule inhibitor of menin and is used to treat children and adults with relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene translocation. Revumenib is associated with mild-to-moderate elevations in serum aminotransferase levels during therapy but has not been linked to episodes of clinically apparent liver injury with jaundice.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on findings in animals and its mechanism of action [see Clinical Pharmacology (12.1) ], REVUFORJ can cause fetal harm when administered to a pregnant woman. There are no available data on REVUFORJ use in pregnant women to evaluate for a drug-associated risk. In an animal reproduction study, oral administration of revumenib to pregnant rats during the period of organogenesis caused adverse developmental outcomes, including embryo-fetal mortality, malformations, and altered fetal growth at maternal exposures approximately 0.5 times the human exposure (AUC) at the recommended dose (see Data). Advise pregnant women of the potential risk to a fetus. In the U.S.
general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Data Animal Data In an embryo-fetal development study, revumenib was administered once daily via oral gavage at doses of 30, 100, and 300 mg/kg/day to pregnant rats during the period of organogenesis (gestation days 6-17). Decreased maternal body weight gain and adverse embryo-fetal findings including decreases in the number of live fetuses, increases in resorptions and post-implantation loss, and decreases in fetal body weight were observed at all doses.
At 300 mg/kg/day, total litter resorption and eye malformations were observed. At the dose of 30 mg/kg/day in rats, the maternal exposures (AUC) were approximately 0.5 times the human exposure at the recommended dose.
Breastfeeding (LactMed)
No information is available on the use of revumenib during breastfeeding. Because it is 90% bound to plasma proteins, the amount in milk is likely to be very low. The manufacturer recommends that breastfeeding be discontinued during therapy and for 1 week after the last dose.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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