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Full Prescribing Information  |  Med Guide/IFU

Full Prescribing Information

Med Guide/IFU

Important Safety Information

Patient Site

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Revuforj® (revumenib) Logo

Revuforj is a menin inhibitor indicated for the treatment of relapsed or refractory acute leukemia with a
lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients 1 year and older.

Dosing & Management

Convenience of an oral, targeted treatment

All Revuforj doses should be taken:

Revuforj® (revumenib) Oral Twice-Daily Dosing

orally, twice daily
at about the same time each day
(~12 hours apart)

Revuforj® (revumenib) With or Without Food

fasted* or
with a low-fat meal
(~400 calories and
25% or less fat)

In the clinical trial protocol, fasted was defined as at least 2 hours after a meal and 1 hour before the next meal.

Continue Revuforj until disease progression or unacceptable toxicity

>6
MONTHS

For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for a clinical response

Image of a yellow line
Image of a yellow line

The recommended dose of Revuforj varies by patient weight and concomitant use of strong CYP3A4 inhibitors

Revuforj® (revumenib) Bottles With Tablets

Bottles and tablets shown are not actual size.

  • If needed, attain the desired dose by combining different strengths of Revuforj tablets

  • 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

Review the Instructions for Use with patients and/or their respective caregivers.

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.

Recommended starting
dose and dose
modifications for
patients 1 year
and older

All doses should be taken orally twice daily fasted or with a low-fat meal

Without
a strong CYP3A4 inhibitor

With
a strong CYP3A4 inhibitor†

Dose
level

Patients
≥40 kg

Patients
<40 kg*

Starting dose

270 mg BID

160 mg BID

160 mg/m2 BID

95 mg/m2 BID

Reduced dose

160 mg BID

110 mg BID

95 mg/m2 BID

65 mg/m2 BID

BID=twice a day; BSA=body surface area; CYP3A4=cytochrome P450 3A4.

  • See below for the recommended dose and the reduced dose for patients weighing <40 kg with a BSA ≤1.4 m2.

  • 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.

Revuforj dosage for recommended dose and reduced dose

BSA
(m2)

160
mg/m2

95
mg/m2

65
mg/m2

1.4

220 mg
BID

135 mg
BID

100 mg
BID

1.3

220 mg
BID

135 mg
BID

75 mg
BID

1.2

185 mg
BID

110 mg
BID

75 mg
BID

1.1

185 mg
BID

110 mg
BID

75 mg
BID

1

160 mg
BID

100 mg
BID

50 mg
BID

0.9

135 mg
BID

75 mg
BID

50 mg
BID

0.8

135 mg
BID

75 mg
BID

50 mg
BID

0.7

110 mg
BID

50 mg
BID

50 mg
BID

0.6

100 mg
BID

50 mg
BID

25 mg
BID

0.5

75 mg
BID

50 mg
BID

25 mg
BID

0.4

50 mg
BID

25 mg
BID

25 mg
BID

For patients who are unable to swallow Revuforj tablets whole:


Review the Instructions for Use with patients and their caregivers for how to prepare and break apart the Revuforj tablets in water

Monitoring guidance for before and during treatment

Icon of blood

Prior to starting Revuforj, reduce the white blood cell count to less than 25 Gi/L

Icon of a testing tube with blood

Assess blood counts, electrolytes, and liver enzymes

prior to the initiation of Revuforj and monthly thereafter
Icon of a heartbeat

Perform electrocardiogram (ECG)
prior to the initiation of Revuforj, at least once a week for the first 4 weeks, and at least monthly thereafter

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.

  • Do not initiate Revuforj in patients with QTcF >450 msec

  • Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to treatment with Revuforj

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.

Verify pregnancy status in females of reproductive potential within 7 days prior to initiating Revuforj
Two bottles of medicine

Other drugs may affect the safety and efficacy of Revuforj

Advise patients to inform their healthcare providers of all concomitant medications, including over-the-counter products and supplements.

Concomitant use of
Revuforj with:

Concomitant use of
Revuforj with:

Concomitant use of
Revuforj with:

Effect

Effect

Effect

Action

Action

Action

Strong CYP3A4 inhibitors

Strong or moderate
CYP3A4 inducers

QTc-prolonging drugs

Increases revumenib systemic exposure, which may increase the risk of adverse reactions

May decrease revumenib and increase M1 systemic exposure, which may reduce Revuforj efficacy or increase the risk of QT prolongation associated with the M1 metabolite

May result in an increase in the QTc interval and adverse reactions associated with QTc interval prolongation

If concomitant use of strong CYP3A4 inhibitors is required, reduce the Revuforj dose*

Avoid concomitant use
with Revuforj

Avoid concomitant use with Revuforj†

See Section 2.2 of the Full Prescribing Information.

If concomitant use is unavoidable, obtain ECGs when initiating, during concomitant use, and as clinically indicated. Withhold Revuforj if the QTc interval is >480 msec. Restart Revuforj after the QTc interval returns to ≤480 msec.

Doses can be modified as needed to help manage adverse reactions

Select an adverse reaction below to see the recommended action

Recommended action:

  • If differentiation syndrome is suspected, administer systemic corticosteroids and initiate hemodynamic monitoring until symptom resolution and for a minimum of 3 days

  • 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. Resume Revuforj at the same dose when signs and symptoms improve to Grade 1* or lower

Recommended action:

  • 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

Recommended action:

  • Interrupt Revuforj

  • Check electrolyte levels. Correct hypokalemia and hypomagnesemia

  • Restart Revuforj at the same dose level after the QTc interval returns to less than or equal to 480 msec

Recommended action:

  • Interrupt Revuforj

  • Check electrolyte levels. Correct hypokalemia and hypomagnesemia

  • Restart Revuforj at the reduced dose level† after the QTc interval returns to less than or equal to 480 msec

Recommended action:

  • Permanently discontinue Revuforj

Recommended action:

  • Supplement potassium and/or magnesium

  • Continue Revuforj

Recommended action:

  • 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

Recommended action:

  • 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

Recommended action:

  • 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†

Recommended action:

  • Permanently discontinue Revuforj

Other actions may be necessary based on your clinical judgment.

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 in the Full Prescribing Information for the reduced dose levels.

NEXT: Resources

Reference: Revuforj® [Prescribing Information]. Waltham, MA: Syndax Pharmaceuticals Inc.; November 2024.

IMPORTANT SAFETY
INFORMATION AND INDICATION

WARNING: DIFFERENTIATION SYNDROME

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.

WARNINGS AND PRECAUTIONS

Differentiation syndrome: Revuforj can cause fatal or life-threatening differentiation syndrome (DS). Symptoms of DS, including those seen in patients treated with Revuforj, include fever, dyspnea, hypoxia, peripheral edema, pleuropericardial effusion, acute renal failure, and/or hypotension. In clinical trials, DS occurred in 39 (29%) of 135 patients treated with Revuforj. DS was Grade 3 or 4 in 13% of patients and fatal in one. The median time to onset was 10 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 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 IV every 12 hours in adults or dexamethasone 0.25-mg/kg/dose IV 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.


QTc interval prolongation: In the clinical trials, QTc interval prolongation was reported as an adverse reaction in 39 (29%) of 135 patients treated with Revuforj. QTc interval prolongation was Grade 3 in 12% of patients. The heart-rate corrected QT interval (using Fridericia’s method) (QTcF) was greater than 500 msec in 8%, and the increase from baseline QTcF was greater than 60 msec in 18%. Revuforj dose reduction was required for 5% of patients due to QTc interval prolongation. QTc prolongation occurred in 16% of the 31 patients less than 17 years old, 33% of the 88 patients 17 years to less than 65 years old, and in 50% of the 16 patients 65 years or older.


Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to treatment with Revuforj. Perform an electrocardiogram (ECG) prior to initiation of Revuforj, and do not initiate Revuforj in patients with QTcF >450 msec. Perform an ECG at least once weekly for the first 4 weeks and at least monthly thereafter. 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 with drugs known to prolong the QTc interval may increase the risk of QTc interval prolongation.

  • Interrupt Revuforj if QTcF increases >480 msec and <500 msec, and restart Revuforj at the same dose twice daily after the QTcF interval returns to ≤480 msec
  • Interrupt Revuforj if QTcF increases >500 msec or by >60 msec from baseline, and restart Revuforj twice daily at the lower-dose level after the QTcF interval returns 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

Embryo-fetal toxicity: Revuforj can cause fetal harm when administered to a pregnant woman. 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 of Revuforj.


ADVERSE REACTIONS

Fatal adverse reactions occurred in 4 (3%) patients who received Revuforj, including 2 with differentiation syndrome, 1 with hemorrhage, and 1 with sudden death.


Serious adverse reactions were reported in 99 (73%) patients. The most frequent serious adverse reactions (≥5%) were infection (24%), febrile neutropenia (19%), bacterial infection (17%), differentiation syndrome (12%), hemorrhage (9%), and thrombosis (5%).


The most common adverse reactions (≥20%) including laboratory abnormalities, were hemorrhage (53%), nausea (51%), phosphate increased (50%), musculoskeletal pain (42%), infection (41%), aspartate aminotransferase increased (37%), febrile neutropenia (35%), alanine aminotransferase increased (33%), parathyroid hormone intact increased (33%), bacterial infection (31%), diarrhea (30%), differentiation syndrome (29%), electrocardiogram QT prolonged (29%), phosphate decreased (25%), triglycerides increased (25%), potassium decreased (24%), decreased appetite (24%), constipation (23%), edema (23%), viral infection (23%), fatigue (22%), and alkaline phosphatase increased (21%).


DRUG INTERACTIONS

Drug interactions can occur when Revuforj is concomitantly used with:

  • Strong CYP3A4 inhibitors: reduce Revuforj dose

  • Strong or moderate CYP3A4 inducers: avoid concomitant use with Revuforj

  • QTc-prolonging drugs: avoid concomitant use with Revuforj. If concomitant use is unavoidable, obtain ECGs when initiating, during concomitant use, and as clinically indicated. Withhold Revuforj if the QTc interval is >480 msec.
    Restart Revuforj after the QTc interval returns to ≤480 msec


SPECIAL POPULATIONS

Lactation: advise lactating women not to breastfeed during treatment with Revuforj and for 1 week after the last dose.


Pregnancy and testing: Revuforj can cause fetal harm when administered to a pregnant woman. Verify pregnancy status in females of reproductive potential within 7 days prior to initiating Revuforj.


Pediatric: monitor bone growth and development in pediatric patients.


Geriatric: compared to younger patients, the incidences of QTc prolongation and edema were higher in patients 65 years and older.


Infertility: based on findings in animals, Revuforj may impair fertility. The effects on fertility were reversible.


To report SUSPECTED ADVERSE REACTIONS, contact Syndax Pharmaceuticals at 1-888-539-3REV or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.


INDICATION

Revuforj® (revumenib) is a menin inhibitor indicated for the treatment of relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients 1 year and older.


Please see Full Prescribing Information, including BOXED WARNING.

IMPORTANT SAFETY
INFORMATION AND INDICATION

IMPORTANT SAFETY
INFORMATION AND INDICATION

WARNING: DIFFERENTIATION SYNDROME

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.