Revuforj
revumenib · Tablet, Film Coated · Oral
Uses
1 INDICATIONS AND USAGE REVUFORJ is a menin inhibitor indicated for: the treatment of relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene ( KMT2A ) translocation as determined by an FDA-authorized test in adult and pediatric patients 1 year and older. ( 1 ) the treatment of relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 ( NPM1 ) mutation in adult and pediatric patients 1 year and older who have no satisfactory alternative treatment options. ( 1 ) Relapsed or Refractory Acute Leukemia REVUFORJ is indicated for the treatment of relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene ( KMT2A ) translocation as determined by an FDA-authorized test in adult and pediatric patients 1 year and older. REVUFORJ is indicated for the treatment of relapsed or refractory acute myeloid leukemia with a susceptible nucleophosmin 1 ( NPM1 ) mutation [see Dosage and Administration (2.1) , Clinical Pharmacology (12.1) , and Clinical Studies (14.1) ] in adult and pediatric patients 1 year and older who have no satisfactory alternative treatment options.
Dosage and administration
Select patients for treatment with REVUFORJ based on the presence of a KMT2A translocation or an NPM1 mutation. ( 2.1 ) Administer REVUFORJ orally twice daily fasted or with a low-fat meal at approximately the same time each day. ( 2.2 ) See Full Prescribing Information for recommended REVUFORJ dosage regimen, dosage modifications, and administration instructions. ( 2.2 , 2.3 ) 2.1 Patient Selection Relapsed or Refractory Acute Leukemia with a KMT2A Translocation Select patients for treatment with REVUFORJ based on the presence of a KMT2A translocation [see Clinical Studies (14.1) ] . Information on FDA authorized tests for the detection of a KMT2A translocation to determine eligibility for treatment is available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?id=DEN240067 Relapsed or Refractory Acute Myeloid Leukemia with an NPM1 mutation Select patients for treatment with REVUFORJ based on the presence of an NPM1 mutation [see Clinical Pharmacology (12.1 ) and Clinical Studies (14.2) ] . An FDA-approved companion diagnostic for the detection of an NPM1 mutation is not currently available. 2.2 Recommended Dosage The recommended dosage of REVUFORJ varies by patient weight and concomitant use of strong CYP3A4 inhibitors. See Table 1 for the recommended dosage for patients 1 year and older. Do not start REVUFORJ until the WBC is reduced to less than 25 Gi/L. Continue REVUFORJ until disease progression or unacceptable toxicity. For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response. Table 1. REVUFORJ Recommended Dosage for Patients 1 Year and Older *See Table 2 for the total tablet dosage by BSA (body surface area) for patients weighing less than 40 kg. Patient Weight Without Strong CYP3A4 Inhibitors With Strong CYP3A4 Inhibitors 40 kg or more 270 mg orally twice daily 160 mg orally twice daily Less than 40 kg 160 mg/m 2 orally twice daily* 95 mg/m 2 orally twice daily* Table 2: Recommended Dosage using Tablets* for Patients Weighing Less than 40 kg * If needed, attain the desired dose by combining different strengths of REVUFORJ tablets. BSA (m 2 ) REVUFORJ Dosage for 160 mg/m 2 REVUFORJ Dosage for 95 mg/m 2 1.4 220 mg twice daily 135 mg twice daily 1.3 220 mg twice daily 135 mg twice daily 1.2 185 mg twice daily 110 mg twice daily 1.1 185 mg twice daily 110 mg twice daily 1 160 mg twice daily 100 mg twice daily 0.9 135 mg twice daily 75 mg twice daily 0.8 135 mg twice daily 75 mg twice daily 0.7 110 mg twice daily 50 mg twice daily 0.6 100 mg twice daily 50 mg twice daily 0.5 75 mg twice daily 50 mg twice daily 0.4 50 mg twice daily 25 mg twice daily If the strong CYP3A4 inhibitor is discontinued, increase the REVUFORJ dose after at least 5 half-lives of the strong CYP3A4 inhibitor to the recommended dosage without strong CYP3A4 inhibitors (Table 1). Concurrent use of standard intrathecal chemotherapy prophylaxis is recommended for patients with risk of central nervous system relapse. Administration: Correct hypokalemia, hypomagnesemia, and other electrolyte abnormalities prior to treatment. Administer REVUFORJ twice daily fasted or with a low-fat meal (e.g., meals with approximately 400 calories, 25% or less fat). Administer REVUFORJ orally around the same time each day. Advise patients to swallow tablets whole and to not cut or chew tablets. If patients are unable to swallow tablets, they may be crushed and dispersed in water and taken within 2 hours of preparation [see Instructions for Use ] . If a dose of REVUFORJ is missed or not taken at the usual time, administer the dose as soon as possible on the same day and at least 12 hours prior to the next scheduled dose. Return to the normal schedule the following day. Do not administer 2 doses within 12 hours. 2.3 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 (5.2) and Adverse Reactions (6.1) ] . 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. Table 3. Recommended Management and Dosage Modifications for Adverse Reactions *Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening. Severity as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0). **See Tables 4, 5 and 6 for the reduced dose levels. Adverse reaction Recommended action Differentiation Syndrome [see Warnings and Precautions (5.1) ] If differentiation syndrome is suspected, administer systemic corticosteroids and initiate hemodynamic monitoring until symptom resolution and for a minimum of 3 days. [see Warnings and Precautions (5.1) ] . Interrupt REVUFORJ if severe signs and/or symptoms persist for more than 48 hours after initiation of systemic corticosteroids, or earlier for life-threatening symptoms such as pulmonary symptoms requiring ventilator support [see Warnings and Precautions (5.1) ] . Resume REVUFORJ at the same dose when signs and symptoms improve to Grade 1* or lower. Noninfectious leukocytosis Initiate treatment with hydroxyurea in patients with an elevated or rapidly rising leukocyte count. Add leukapheresis if clinically indicated. Taper hydroxyurea only after leukocytosis improves or resolves. QTc interval greater than 480 msec to 500 msec [see Warnings and Precautions(5.2) ] Interrupt REVUFORJ. Check electrolyte levels. Correct hypokalemia and hypomagnesemia [see Warnings and Precautions (5.2) ] . Restart REVUFORJ at the same dose level after the QTc interval returns to less than or equal to 480 msec.
Dosage forms and strengths
Tablets: 25 mg, 110 mg, 160 mg ( 3 ) Tablets: 25 mg of revumenib: Pink modified oval film-coated tablet debossed with “S” on one side and “25” on the other side. 110 mg of revumenib: Beige modified oval film-coated tablet debossed with “S” on one side and “110” on the other side. 160 mg of revumenib: Purple modified oval film-coated tablet debossed with “S” on one side and “160” on the other side.
Contraindications
None. None. ( 4 )
Warnings and precautions
Embryo-Fetal Toxicity : Can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of potential risk to a fetus and to use effective contraception . ( 5.3 , 8.1 , 8.3 ) 5.1 Differentiation Syndrome REVUFORJ can cause fatal or life-threatening differentiation syndrome (DS). 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 (6.1) ] . Among those with a KMT2A translocation, DS occurred in 33% of patients with acute myeloid leukemia (AML), 33% of patients with mixed-phenotype acute leukemia (MPAL), and 9% of patients with acute lymphoblastic leukemia (ALL); DS occurred in 18% of patients with NPM1 mutated AML. DS was Grade 3 or 4 in 12% of patients and fatal in two patients. The median time to initial onset was 9 days (range 3-41 days). Some patients experienced more than 1 DS event. Treatment interruption was required for 7% of patients, and treatment was withdrawn for 1%. Reduce the white blood cell count (WBC) to less than 25 Gi/L prior to starting REVUFORJ. If DS is suspected, immediately initiate treatment with systemic corticosteroids (e.g., dexamethasone 10 mg intravenously every 12 hours in adults or dexamethasone 0.25 mg/kg/dose intravenously every 12 hours in pediatric patients weighing less than 40 kg) for a minimum of 3 days and until resolution of signs and symptoms. Institute supportive measures and hemodynamic monitoring until improvement. Interrupt REVUFORJ if severe signs and/or symptoms persist for more than 48 hours after initiation of systemic corticosteroids, or earlier if life-threatening symptoms occur such as pulmonary symptoms requiring ventilator support. Restart steroids promptly if DS recurs after tapering corticosteroids [see Dosage and Administration (2.3) ]. 5.2 QTc Interval Prolongation and Torsades de Pointes REVUFORJ can cause QT (QTc) interval prolongation and Torsades de Pointes [see Clinical Pharmacology (12.2) ] . Of the 241 patients treated with REVUFORJ at the recommended dosage for relapsed or refractory acute leukemia in clinical trials, QTc interval prolongation was reported as an adverse reaction in 86 (36%) of patients. QTc interval prolongation was Grade 3 in 15% and Grade 4 in 2%. The heart-rate corrected QT interval (using Fridericia’s method) (QTcF) was greater than 500 msec in 10%, and the increase from baseline QTcF was greater than 60 msec in 24%. REVUFORJ dose reduction was required for 7% due to QTc interval prolongation [see Adverse Reactions (6.1)] . QTc prolongation occurred in 21% of the 34 patients less than 17 years old, 35% of the 146 patients 17 years to less than 65 years old, and in 46% of the 61 patients 65 years or older. One patient had a fatal outcome of cardiac arrest, and one patient had nonsustained Torsades de Pointes. Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to and throughout treatment with REVUFORJ. Perform an ECG prior to initiation of treatment with REVUFORJ, and do not initiate REVUFORJ in patients with QTcF > 450 msec. Perform an ECG at least once a week for the first 4 weeks on treatment, and at least monthly thereafter [see Dosage and Administration (2.3) ] . In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring may be necessary. Concomitant use of REVUFORJ with drugs known to prolong the QTc interval may increase the risk of QTc interval prolongation. [see Drug Interactions (7.1) , Clinical Pharmacology (12.2) ] . Interrupt REVUFORJ if QTcF increases to greater than 480 msec and less than 500 msec, and restart REVUFORJ at the same dose twice daily after the QTcF interval returns to less than or equal to 480 msec. Interrupt REVUFORJ if QTcF increases to greater than 500 msec or by > 60 msec from baseline, and restart REVUFORJ twice daily at the lower dose level after the QTcF interval returns to less than or equal to 480 msec. Permanently discontinue REVUFORJ in patients with ventricular arrhythmias and in those who develop QTc interval prolongation with signs or symptoms of life- threatening arrhythmia [see Dosage and Administration (2.3) ] . 5.3 Embryo-Fetal Toxicity Based on findings in animals and its mechanism of action, REVUFORJ can cause fetal harm when administered to a pregnant woman. 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. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with REVUFORJ and for 4 months after the last dose [see Use in Specific Populations ( 8.1 , 8.3 ) and Clinical Pharmacology (12.3) ].
Side effects
The following clinically significant adverse reactions are described elsewhere in the labeling: Differentiation Syndrome [see Warnings and Precautions (5.1) ] QTc Interval Prolongation and Torsades de Pointes [see Warnings and Precautions (5.2) ] The most common adverse reactions (≥ 20%) including laboratory abnormalities, are phosphate increased, hemorrhage, nausea, infection without identified pathogen, aspartate aminotransferase increased, alanine aminotransferase increased, creatinine increased, musculoskeletal pain, febrile neutropenia, electrocardiogram QT prolonged, potassium decreased, parathyroid hormone intact increased, alkaline phosphatase increased, diarrhea, bacterial infection, triglycerides increased, differentiation syndrome, fatigue, edema, viral infection, phosphate decreased, decreased appetite, and constipation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Syndax Pharmaceuticals, Inc., at 1-888-539-3REV or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of REVUFORJ reflects exposure in 241 patients (207 adult and 34 pediatric patients) with relapsed or refractory (R/R) acute leukemia with a KMT2A translocation or an NPM1 mutation treated with REVUFORJ at a dose approximately equivalent to 160 mg in adults orally twice daily with a strong CYP3A4 inhibitor [see Clinical Studies (14) ] . The median duration of exposure to REVUFORJ was 2.5 months (range < 1 to 40 months), and 10% of patients were exposed for more than 6 months. Fatal adverse reactions occurred in 9 (4%) patients who received REVUFORJ, including 4 with sudden death, 2 with differentiation syndrome, 2 with hemorrhage, and 1 with cardiac arrest. Serious adverse reactions were reported in 184 (76%) patients. The most frequent serious adverse reactions (≥ 10%) were infection (29%), febrile neutropenia (20%), bacterial infection (15%), differentiation syndrome (13%), and hemorrhage (11%). Adverse reactions leading to dose interruption occurred in 49% of patients. The most common adverse reactions (≥ 5%) leading to dose interruption were electrocardiogram QT prolonged, infection, febrile neutropenia, differentiation syndrome, nausea, and hypokalemia. Adverse reactions leading to dose reduction occurred in 12% of patients who received REVUFORJ. Adverse reactions leading to a dose reduction (≥ 5%) included electrocardiogram QT prolonged. Adverse reactions leading to permanent discontinuation occurred in 20% of patients. Adverse reactions resulting in permanent discontinuation (> 1%) included infection. The most common (≥ 20%) adverse reactions were phosphate increased, hemorrhage, nausea, infection without identified pathogen, aspartate aminotransferase increased, alanine aminotransferase increased, creatinine increased, musculoskeletal pain, febrile neutropenia, electrocardiogram QT prolonged, potassium decreased, parathyroid hormone intact increased, alkaline phosphatase increased, diarrhea, bacterial infection, triglycerides increased, differentiation syndrome, fatigue, edema, viral infection, phosphate decreased, decreased appetite, and constipation. The common adverse reactions are summarised in Table 7. Table 7. Adverse Reactions Reported in ≥ 20% (Any Grade) or ≥ 5% (Grade 3 or 4) in Patients with R/R Acute Leukemia # Includes the following fatal adverse reactions: DS (n=2); hemorrhage (n=2) a – Includes nausea and vomiting b – includes diarrhea, colitis, and neutropenic colitis c – includes epistaxis, contusion, petechiae, gingival bleeding, hematoma, hemoptysis, hemorrhoidal hemorrhage, mouth hemorrhage, hematuria, ecchymosis, hemorrhage intracranial, subdural hematoma, upper gastrointestinal hemorrhage, gastrointestinal hemorrhage, vaginal hemorrhage, post- procedural hemorrhage, rectal hemorrhage, subarachnoid hemorrhage, vitreous hemorrhage, catheter site hemorrhage, conjunctival hemorrhage, hematochezia, melaena, retinal hemorrhage, anal hemorrhage, brain stem hemorrhage, cystitis hemorrhagic, eye hematoma, genital contusion, injection site hematoma, lower gastrointestinal hemorrhage, mucosal hemorrhage, oral blood blister, oral contusion, oral purpura, pulmonary hemorrhage, shock hemorrhagic, spinal subdural hematoma d – includes disseminated intravascular coagulation, pulmonary embolism, cerebrovascular accident, superficial vein thrombosis, deep vein thrombosis, acute myocardial infarction, cerebral infarction, embolism, hemorrhoids thrombosed, medical device site thrombosis, myocardial infarction, renal infarction, splenic infarction, thrombosis, and transient ischaemic attack e – includes pneumonia, sepsis, urinary tract infection, septic shock, sinusitis, skin infection, upper respiratory tract infection, osteomyelitis, device related infection, enterocolitis infectious, conjunctivitis, hordeolum, rhinitis, acute sinusitis, diverticulitis, endocarditis, perirectal abscess, rectal abscess, tooth abscess, abscess limb, appendicitis, bronchitis, epididymitis, eye infection, gastroenteritis, infection, mucosal infection, neutropenic sepsis, rash pustular, retinitis, shock, sialadenitis, soft tissue infection, tooth infection, vascular device infection f – includes bacteraemia, clostridium difficile infection, cellulitis, escherichia bacteremia, paronychia, staphylococcal bacteremia, streptococcal bacteremia, alpha hemolytic streptococcal infection, clostridium difficile colitis, clostridium test positive, enterobacter infection, enterobacter sepsis, enterococcal bacteremia, escherichia urinary tract infection, pseudomonal bacteremia, pseudomonas infection, skin bacterial infection, bacteriuria, cellulitis staphylococcal, cornyebacterium bacteremia, enterobacter bacteremia, enterococcal in…
Drug interactions
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) ].
Use in specific populations
Lactation: Advise not to breastfeed ( 8.2 ) 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. 8.2 Lactation Risk Summary There are no data on the presence of revumenib or its metabolites in human milk or the effects on the breastfed child or milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with REVUFORJ and for 1 week after the last dose. 8.3 Females and Males of Reproductive Potential Based on findings in animals and its mechanism of action, REVUFORJ can cause fetal harm when administered to pregnant women [ see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify pregnancy status in females of reproductive potential within 7 days prior to initiating REVUFORJ. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with REVUFORJ and for 4 months after the last dose. Males Advise males of reproductive potential to use effective contraception during treatment with REVUFORJ and for 4 months after the last dose. Infertility Females and Males Based on findings in animals, REVUFORJ may impair fertility. The effects on fertility were reversible [see Nonclinical Toxicology (13.1) ] . 8.4 Pediatric Use The safety and efficacy of REVUFORJ have been established in pediatric patients 1 year and older with relapsed or refractory acute leukemia with a KMT2A translocation or an NPM1 mutation. Use of REVUFORJ for this indication is supported by evidence from adequate and well-controlled trials in adults and pediatric patients [see Clinical Studies (14) ] and additional pharmacokinetic and safety data in pediatric patients [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3) ] . The patients included 25 infants (age < 2 years), 78 children (age 2 to < 12 years) and 29 adolescents (age 12 to < 17 years). The recommended dosage in patients weighing less than 40 kg is BSA-based. The safety and efficacy of REVUFORJ in pediatric patients less than 1 year old have not been established . Animal Data In a repeat dose toxicity study in 6-7 week-old rats treated with revumenib at 75, 150, or 300 mg/kg/day for 13 weeks, an irreversible increase in femur growth plate closure was observed at revumenib exposures approximately 2 times the human exposure (AUC) at the recommended dose. Based on the findings in animals, monitor bone growth and development in pediatric patients. 8.5 Geriatric Use Of the 241 patients with relapsed or refractory acute leukemia with a KMT2A translocation or an NPM1 mutation in clinical studies of REVUFORJ, 61 (25%) patients were 65 years of age and older and 25 (10%) patients were 75 years of age and older [see Clinical Studies (14) ] . No overall differences were observed in the effectiveness of REVUFORJ between patients who were 65 years and older and younger patients [see Clinical Studies (14.1) and Clinical Pharmacology (12.3) ] . Compared to younger patients, the incidences of QTc prolongation and edema were higher in patients 65 years and older [see Warnings and Precautions (5.2) ].
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.
Pediatric use
8.4 Pediatric Use The safety and efficacy of REVUFORJ have been established in pediatric patients 1 year and older with relapsed or refractory acute leukemia with a KMT2A translocation or an NPM1 mutation. Use of REVUFORJ for this indication is supported by evidence from adequate and well-controlled trials in adults and pediatric patients [see Clinical Studies (14) ] and additional pharmacokinetic and safety data in pediatric patients [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3) ] . The patients included 25 infants (age < 2 years), 78 children (age 2 to < 12 years) and 29 adolescents (age 12 to < 17 years). The recommended dosage in patients weighing less than 40 kg is BSA-based. The safety and efficacy of REVUFORJ in pediatric patients less than 1 year old have not been established . Animal Data In a repeat dose toxicity study in 6-7 week-old rats treated with revumenib at 75, 150, or 300 mg/kg/day for 13 weeks, an irreversible increase in femur growth plate closure was observed at revumenib exposures approximately 2 times the human exposure (AUC) at the recommended dose. Based on the findings in animals, monitor bone growth and development in pediatric patients.
Geriatric use
8.5 Geriatric Use Of the 241 patients with relapsed or refractory acute leukemia with a KMT2A translocation or an NPM1 mutation in clinical studies of REVUFORJ, 61 (25%) patients were 65 years of age and older and 25 (10%) patients were 75 years of age and older [see Clinical Studies (14) ] . No overall differences were observed in the effectiveness of REVUFORJ between patients who were 65 years and older and younger patients [see Clinical Studies (14.1) and Clinical Pharmacology (12.3) ] . Compared to younger patients, the incidences of QTc prolongation and edema were higher in patients 65 years and older [see Warnings and Precautions (5.2) ].
Description
11 DESCRIPTION REVUFORJ contains revumenib, a menin inhibitor. Revumenib is present as revumenib citrate hydrate with a chemical name of benzamide, N -ethyl-2-[[4-[7-[[trans-4- [(ethylsulfonyl)amino]cyclohexyl]methyl]-2,7-diazaspiro[3.5]non-2-yl]-5-pyrimidinyl]oxy]-5-fluoro- N -[1- methylethyl]-, 2-hydroxypropane-1,2,3-tricarboxylic acid, hydrate (1:1:1). The molecular formula is C32H47FN6O4S●C6H8O7●H2O with a molecular weight 840.96 g/mol. Revumenib citrate hydrate is a white to faint pink solid. Revumenib citrate hydrate is soluble at pH 1.2 and 6.8, and sparingly soluble at pH 4.5. The chemical structure is shown in Figure 1. Figure 1: Chemical structure of Revumenib Citrate REVUFORJ is available as tablets for oral use. Each 25 mg strength tablet contains 25 mg revumenib, equivalent to 33.4 mg revumenib citrate, and the following inactive ingredients: microcrystalline cellulose, dicalcium phosphate, crospovidone, hypromellose, sodium bicarbonate, hydrophobic colloidal silica, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and red iron oxide. Each 110 mg strength tablet contains 110 mg revumenib, equivalent to 146.5 mg revumenib citrate, and the following inactive ingredients: microcrystalline cellulose, dicalcium phosphate, crospovidone, hypromellose, sodium bicarbonate, hydrophobic colloidal silica, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, red iron oxide, and yellow iron oxide. Each 160 mg strength tablet contains 160 mg revumenib equivalent to 213.2 mg revumenib citrate, and the following inactive ingredients: microcrystalline cellulose, dicalcium phosphate, crospovidone, hypromellose, sodium bicarbonate, hydrophobic colloidal silica, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, red iron oxide, and FD&C blue #2/indigo carmine aluminum lake. Chemical Structure of Revumenib Citrate
Mechanism of action
12.1 Mechanism of Action Revumenib is a menin inhibitor that blocks the interaction of both wild-type lysine methyltransferase 2A (KMT2A) and KMT2A fusion proteins with menin. The binding of wild-type KMT2A or KMT2A fusion proteins with menin is involved in NPM1 mutated acute myeloid leukemias and KMT2A - rearranged acute leukemias, respectively, through activation of a leukemogenic transcriptional pathway. Susceptible NPM1 mutations are defined as those that result in loss of the nucleolar localization signal and the insertion of a new nuclear export signal leading to the accumulation of mutant NPM1 in the cytoplasm of AML cells. The most common of such NPM1 mutations in patients with AML are Types A, B, and D. In nonclinical studies using cells that express KMT2A fusions, inhibition of the menin-KMT2A interaction with revumenib altered the transcription of multiple genes including differentiation markers. In nonclinical in vitro and in vivo studies, revumenib demonstrated antiproliferative and antitumor activity in leukemia cells harboring KMT2A fusion proteins. Revumenib also showed antiproliferative activity in vitro in leukemia cells with an NPM1 mutation.
How supplied
25 mg: Pink modified oval film-coated tablet debossed with “S” on one side and “25” on the other side. 30-count bottles with a desiccant and child resistant closure (NDC 73555-500-00) 110 mg: Beige modified oval film-coated tablet debossed with “S” on one side and “110” on the other side. 30-count bottles with a desiccant and child resistant closure (NDC 73555-501-00) 160 mg: Purple modified oval film-coated tablet debossed with “S” on one side and “160” on the other side. 30-count bottles with a desiccant and child resistant closure (NDC 73555-502-00) Store tablets at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Store and dispense in the orginal container.
Storage
Store tablets at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Store and dispense in the orginal container.
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide) and Instructions for Use. Differentiation Syndrome Advise patients of the risks of developing differentiation syndrome as early as 3 days after the start of therapy and during treatment. Ask patients to immediately report any symptoms suggestive of differentiation syndrome, such as fever, cough or difficulty breathing, rash, low blood pressure, rapid weight gain, swelling of their arms or legs, or decreased urinary output, to their healthcare provider for further evaluation [see Boxed Warning and Warnings and Precautions (5.1) ] . Prolonged QT Interval and Torsades de Pointes Advise patients to consult their healthcare provider immediately if they feel faint, lose consciousness, or have signs or symptoms suggestive of arrhythmia. Advise patients with a history of hypokalemia or hypomagnesemia of the importance of monitoring their electrolytes [see Boxed Warning and Warnings and Precautions (5.2) ] . Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to notify their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.3) and Use in Specific Populations (8.1) ]. Advise females of reproductive potential to use effective contraception during treatment with REVUFORJ and for 4 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with REVUFORJ and for 4 months after the last dose [see Use in Specific Populations (8.3) ] . Lactation Advise women not to breastfeed during treatment with REVUFORJ and for 1 week after the last dose [see Use in Specific Populations (8.2) ] . Infertility Advise females and males of reproductive potential of the potential for impaired fertility from REVUFORJ [see Use in Specific Populations (8.3) , Nonclinical Toxicology (13.1) ] . Drug Interactions Advise patients to inform their healthcare providers of all concomitant products, including over-the counter products and supplements [ see Drug Interactions (7.1) ] . Dosing Instructions Advise patients to swallow tablets whole with a cup of water and not to cut or chew tablets. If patients are unable to swallow the tablets, they may be crushed and dispersed in water [see Instructions for Use ]. Instruct patients that, if they miss a dose of REVUFORJ, to take it as soon as possible on the same day, and at least 12 hours prior to the next scheduled dose, and return to the normal schedule the following day [see Dosage and Administration (2.2) ] .
Label text from the FDA structured product label by Syndax Pharmaceuticals, Inc. (revised Feb 4, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Revumenib Citrate in 3 products
Revuforj NDC products (3)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 73555-500 | Revumenib Citrate 25 mg/1 Tablet, Film Coated | Syndax Pharmaceuticals, Inc. | NDA |
| 73555-501 | Revumenib Citrate 110 mg/1 Tablet, Film Coated | Syndax Pharmaceuticals, Inc. | NDA |
| 73555-502 | Revumenib Citrate 160 mg/1 Tablet, Film Coated | Syndax Pharmaceuticals, Inc. | NDA |
Frequently asked questions
What is Revuforj used for?
1 INDICATIONS AND USAGE REVUFORJ is a menin inhibitor indicated for: the treatment of relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene ( KMT2A ) translocation as determined by an FDA-authorized test in adult and pediatric patients 1 year and older. ( 1 ) the treatment of relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 ( NPM1 )…
What are the side effects of Revuforj?
The following clinically significant adverse reactions are described elsewhere in the labeling: Differentiation Syndrome [see Warnings and Precautions (5.1) ] QTc Interval Prolongation and Torsades de Pointes [see Warnings and Precautions (5.2) ] The most common adverse reactions (≥ 20%) including laboratory abnormalities, are phosphate increased, hemorrhage, nausea, infection without identified… See the full label for the complete list.
Who makes Revuforj?
Revuforj is listed by 1 labeler in the FDA NDC directory, including Syndax Pharmaceuticals, Inc..