Revumenib Dosage

Medically reviewed by Drugs.com. Last updated on Jan 16, 2025.

Applies to the following strengths: 25 mg; 110 mg; 160 mg

Usual Adult Dose for Leukemia

Weighing Less Than 40 kg:

Without strong CYP450 3A4 inhibitors: 160 mg/m2 orally twice a day
With strong CYP450 3A4 inhibitors: 95 mg/m2 orally twice a day

Weighing 40 kg or More:

Without strong CYP450 3A4 inhibitors: 270 mg orally twice a day
With strong CYP450 3A4 inhibitors: 160 mg orally twice a day

Recommended dosage using tablets for patients weighing less than 40 kg:
Dosage for 160 mg/m2:

BSA 0.4 m2: 50 mg orally twice a day
BSA 0.5 m2: 75 mg orally twice a day
BSA 0.6 m2: 100 mg orally twice a day
BSA 0.7 m2: 110 mg orally twice a day
BSA 0.8 through 0.9 m2: 135 mg orally twice a day
BSA 1 m2: 160 mg orally twice a day
BSA 1.1 through 1.2 m2: 185 mg orally twice a day
BSA 1.3 through 1.4 m2: 220 mg orally twice a day

Dosage for 95 mg/m2:

BSA 0.4 m2: 25 mg orally twice a day
BSA 0.5 through 0.7 m2: 50 mg orally twice a day
BSA 0.8 through 0.9 m2: 75 mg orally twice a day
BSA 1 m2: 100 mg orally twice a day
BSA 1.1 through 1.2 m2: 110 mg orally twice a day
BSA 1.3 through 1.4 m2: 135 mg orally twice a day

Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

The recommended dosage in patients weighing less than 40 kg is BSA-based.
The dose of this drug depends on weight and the use of strong CYP450 3A4 inhibitors.
If the strong CYP450 3A4 inhibitor is discontinued, increase the dose of this drug to the recommended level (i.e., dosage without strong CYP450 3A4 inhibitors) after at least 5 half-lives of the strong CYP450 3A4 inhibitor (i.e., posaconazole, itraconazole, and voriconazole).
Refrain from starting this drug until the WBC is reduced to below 25 Gi/L.
For patients without disease progression or unacceptable toxicity, it is recommended to treat for at least 6 months to allow time for clinical response.

Use: For the treatment of relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene translocation

Usual Pediatric Dose for Leukemia

1 YEAR AND OLDER:
Weighing Less Than 40 kg:

Without strong CYP450 3A4 inhibitors: 160 mg/m2 orally twice a day
With strong CYP450 3A4 inhibitors: 95 mg/m2 orally twice a day

Weighing 40 kg or More:

Without strong CYP450 3A4 inhibitors: 270 mg orally twice a day
With strong CYP450 3A4 inhibitors: 160 mg orally twice a day

Recommended dosage using tablets for patients weighing less than 40 kg:
Dosage for 160 mg/m2:

BSA 0.4 m2: 50 mg orally twice a day
BSA 0.5 m2: 75 mg orally twice a day
BSA 0.6 m2: 100 mg orally twice a day
BSA 0.7 m2: 110 mg orally twice a day
BSA 0.8 through 0.9 m2: 135 mg orally twice a day
BSA 1 m2: 160 mg orally twice a day
BSA 1.1 through 1.2 m2: 185 mg orally twice a day
BSA 1.3 through 1.4 m2: 220 mg orally twice a day

Dosage for 95 mg/m2:

BSA 0.4 m2: 25 mg orally twice a day
BSA 0.5 through 0.7 m2: 50 mg orally twice a day
BSA 0.8 through 0.9 m2: 75 mg orally twice a day
BSA 1 m2: 100 mg orally twice a day
BSA 1.1 through 1.2 m2: 110 mg orally twice a day
BSA 1.3 through 1.4 m2: 135 mg orally twice a day

Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

The recommended dosage in patients weighing less than 40 kg is BSA-based.
The dose of this drug depends on weight and the use of strong CYP450 3A4 inhibitors.
If the strong CYP450 3A4 inhibitor is discontinued, increase the dose of this drug to the recommended level (i.e., dosage without strong CYP450 3A4 inhibitors) after at least 5 half-lives of the strong CYP450 3A4 inhibitor (i.e., posaconazole, itraconazole, and voriconazole).
Refrain from starting this drug until the WBC is reduced to below 25 Gi/L.
For patients without disease progression or unacceptable toxicity, it is recommended to treat for at least 6 months to allow time for clinical response.

Use: For the treatment of relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene translocation

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

Dosage Reduction for Adverse Reactions in Patients NOT on Strong CYP450 3A4 Inhibitors:

Weight less than 40 kg at starting dose 160 mg/m2: Reduce dose to 95 mg/m2 orally twice a day.
Weight 40 kg or greater at starting dose 270 mg: Reduce dose to 160 mg orally twice a day.

Dosage Reduction for Adverse Reactions in Patients on Strong CYP450 3A4 Inhibitors:

Weight less than 40 kg at starting dose 95 mg/m2: Reduce dose to 65 mg/m2 orally twice a day.
Weight 40 kg or greater at starting dose 160 mg: Reduce dose to 110 mg orally twice a day.

Recommended Reduced Dosage Using Tablets for Patients Weighing Less Than 40 kg:
Dosage for 95 mg/m2:

BSA 0.4 m2: 25 mg orally twice a day
BSA 0.5 through 0.7 m2: 50 mg orally twice a day
BSA 0.8 through 0.9 m2: 75 mg orally twice a day
BSA 1 m2: 100 mg orally twice a day
BSA 1.1 through 1.2 m2: 110 mg orally twice a day
BSA 1.3 through 1.4 m2: 135 mg orally twice a day

Dosage for 65 mg/m2:

BSA 0.4 through 0.6 m2: 25 mg orally twice a day
BSA 0.7 through 1 m2: 50 mg orally twice a day
BSA 1.1 through 1.3 m2: 75 mg orally twice a day
BSA 1.4 m2: 100 mg orally twice a day

Dosage Modifications for Adverse Reactions:
Differentiation syndrome:

If differentiation syndrome is suspected, it is recommended to start systemic corticosteroids and hemodynamic monitoring for at least 3 days and until symptoms resolve.
Interrupt therapy if severe signs/symptoms persist after 48 hours of corticosteroids, or earlier if life-threatening symptoms such as pulmonary symptoms requiring ventilator support arise. Resume therapy at the same dose when signs and symptoms improve to grade 1 or lower.

Noninfectious leukocytosis:

Administer hydroxyurea in patients with an elevated or rapidly rising leukocyte count; add leukapheresis if needed.
Taper hydroxyurea only after leukocytosis improves or resolves.

QTc interval greater than 480 to 500 msec:

Interrupt therapy.
Check electrolyte levels; correct hypokalemia and hypomagnesemia.
Restart therapy at the same dose level once the QTc interval returns to 480 msec or less.

QTc interval greater than 500 msec (grade 3):

Interrupt therapy.
Check electrolyte levels; correct hypokalemia and hypomagnesemia.
Restart therapy at the reduced dose level once the QTc interval returns to 480 msec or less.

QTc interval prolongation with signs or symptoms of life-threatening arrhythmia, torsade's de pointes, polymorphic ventricular tachycardia, signs or symptoms of life-threatening arrhythmia (grade 4): Permanently discontinue therapy.

Potassium 3.6 to 3.9 mEq/L, and/or magnesium 1.7 to 1.9 mg/dL or 0.66 to 0.81 mmol/L: Supplement potassium and/or magnesium; continue this drug.

Potassium 3.5 mEq/L or less, and/or magnesium 1.6 mg/dL or less or 0.65 mmol/L or less:

Supplement potassium and/or magnesium and recheck levels within 24 hours.
If potassium is greater than 3.5 mEq/L and/or magnesium is greater than 1.6 mg/dL, continue this drug.
If potassium is less than 3.5 mEq/L and/or magnesium is less than 1.6 mg/dL, hold this drug and continue supplementation; resume this drug at the same dose level when the correction is complete.

Other nonhematological adverse reactions grade 3 or greater:

Interrupt therapy until recovery to grade 1 or baseline.
If recovered in 7 days or less, restart therapy at the same dose level.
If the same grade 3 or greater toxicity recurs, interrupt this drug until recovery to grade 1 or baseline. Restart therapy at the reduced dose level.
If recovered in more than 7 days, restart therapy at the reduced dose level.
If the same grade 3 or greater toxicity recurs, discontinue this drug.

Grade 4 neutropenia or thrombocytopenia:

Interrupt therapy until recovery to grade 2 or lower or baseline.
Restart therapy at the same dose level.
If grade 4 neutropenia or thrombocytopenia recurs without attributable cause, interrupt therapy until recovery to grade 3 or lower. Restart therapy at the reduced dose level.

Grade 3 or higher allergic reactions: Permanently discontinue this drug.

Precautions

US BOXED WARNING:

DIFFERENTIATION SYNDROME: Differentiation syndrome (DS), which can be fatal, has been reported with this drug. 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 DS is suspected, immediately initiate corticosteroid therapy and hemodynamic monitoring until symptoms resolve.

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 1 year.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

Select patient based on the presence of a lysine methyltransferase 2A gene (KMT2A) translocation in bone marrow cells.
A US FDA-approved test for the detection of a KMT2A translocation is not currently available.
Administer fasted or with a low-fat meal (e.g., meals with approximately 400 calories, 25% or less fat), at about the same time each day.
Swallow tablets whole; do not cut or chew tablets.
If unable to swallow the tablets, they can be crushed and dispersed in water and taken within 2 hours of preparation.
If a dose is missed or not taken at the usual time, take the missed dose as soon as possible on the same day, at least 12 hours before the next scheduled dose; resume the normal schedule the following day. Do not administer 2 doses within 12 hours.
Concurrent use of standard intrathecal chemotherapy prophylaxis is recommended for patients at risk of central nervous system relapse.

Storage requirements:

Store at 20C to 25C (68F to 77F) with excursions permitted between 15C to 30C (59F to 86F), in original container until dispensed.

Monitoring:

Cardiovascular: For QTc interval prolongation, ECG (before starting therapy, at least once a week for the first 4 weeks, and at least monthly thereafter)
Hematologic: Blood counts (before starting this drug and monthly thereafter)
Hepatic: Liver enzymes (before starting this drug and monthly thereafter)
Metabolic: Electrolytes (before starting this drug and monthly thereafter)
Musculoskeletal: Bone growth and development in pediatric patients

Patient advice:

Read the US FDA-approved patient labeling (Medication Guide) and Instructions for Use.
This drug may cause differentiation syndrome. If you experience symptoms like fever, cough or difficulty breathing, rash, low blood pressure, rapid weight gain, swelling of your arms or legs, or decreased urinary output, report them immediately to your health care provider for evaluation.
Consult your health care provider immediately if you feel faint, lose consciousness, or experience signs/symptoms suggestive of arrhythmia. If you have a history of hypokalemia or hypomagnesemia, it is important to monitor your electrolytes.
Patients of childbearing potential: Notify your health care provider of a known/suspected pregnancy.
Patients of childbearing potential and males with partners of childbearing potential: Use effective contraception during therapy and for 4 months after the last dose.
Do not breastfeed during therapy and for 1 week after the last dose.