Revumenib

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

• 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 aged 1 year and older
• relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 (NPM1) mutation in adult and pediatric patients aged 1 year and older who have no satisfactory alternative treatment options

Common side effects of Revumenib include:

• bleeding (hemorrhage) 
• changes in liver function tests
• nausea and vomiting 
• swelling in the arms and legs
• muscle pain 
• decreased appetite
• infections, including bacterial and viral infections 
• constipation
• low white blood cell counts with fever 
• tiredness
• diarrhea 

Serious side effects of Revumenib include:

• differentiation syndrome symptoms include fever, dizziness or lightheadedness, cough, fast weight gain, shortness of breath, swelling of arms, legs, neck, groin, or underarm area, severe headache, decreased urination, confusion
• changes in the electrical activity of your heart called QT prolongation.

Rare side effects of Revumenib include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Tablet

• 25 mg
• 110 mg
• 160 mg

Acute leukemia

Adult dosage

Dosing

• Weighing 40 kg and more: 270 mg orally two times a day
• Weighing less than 40 kg: 160 mg/m2 orally two times a day; refer to body surface area (BSA) dosing in pediatric dosing
• Continue until disease progression or unacceptable toxicity
• Treat for at least 6 months to allow time for clinical response in patients without disease progression or unacceptable toxicity

Pediatric dosage

Dosing

• Weighing 40 kg or more: 270 mg orally two times a day
• Weighing below 40 kg: 160 mg/m2 orally two times a day
• Continue until disease progression or unacceptable toxicity
• Treat for at least 6 months to allow time for clinical response in patients without disease progression or unacceptable toxicity

Dosing based on BSA

• 1.3-1.4 m2: 220 mg orally two times a day
• 1.1-1.2 m2: 185 mg orally two times a day
• 1 m2: 160 mg orally two times a day
• 0.8-0.9 m2: 135 mg orally two times a day
• 0.7 m2: 110 mg orally two times a day
• 0.6 m2: 100 mg orally two times a day
• 0.5 m2: 75 mg orally two times a day
• 0.4 m2: 50 mg orally two times a day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Revumenib has no noted severe interactions with any other drugs
• Revumenib has no noted serious interactions with any other drugs
• Revumenib has no noted moderate interactions with any other drugs
• Revumenib has no noted minor interactions with any other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Revumenib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Revumenib?”

Cautions

• Leukocytosis
  • Reduce white blood cell (WBC) count to less than 25 x 109/L before starting therapy
  • Treatment with hydroxyurea may be required; taper only after leukocytosis improves or resolves
  • Add leukapheresis if clinically indicated
• QT prolongation
  • QTc interval prolongation reported
• Monitor electrolytes before starting therapy and monthly after that
  • Correct electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia) before starting therapy
• Monitor ECG before starting therapy, at least once weekly for the first 4 weeks, and then at least monthly thereafter
  • Do not start if QTcF is more than 450 msec
  • More frequent ECG monitoring may be necessary in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or who are taking medications known to prolong the QTc interval
  • Hold, reduce dosage, or discontinue therapy based on severity
• Neutropenia or thrombocytopenia
  • Evaluate CBC before starting therapy and monthly thereafter
  • Hold or reduce dosage based on severity
• Elevated transaminases
  • Monitor liver enzymes before starting therapy and monthly thereafter
  • Hold, reduce dosage, or discontinue based on severity
• Allergic reactions
  • Permanently discontinue if severe allergic reaction occurs
• Embryo-fetal toxicity
  • May cause fetal harm if used during pregnancy
  • Advise pregnant patients of potential fetal risk
  • Effective contraception is recommended during and after treatment in females of reproductive potential and males with female partners of reproductive potential
• Drug interaction overview
  • Revumenib is a moderately sensitive CYP3A4 substrate
  • Strong CYP3A4 inhibitors
    • Reduce revumenib dosage if coadministered
    • May increase revumenib exposure and risk of adverse reaction (e.g., QT prolongation)
  • Strong or moderate CYP3A4 inducers
    • Avoid concomitant use
  • May decrease revumenib exposure resulting in reduced efficacy; may also increase metabolite (M1) exposure and risk of QTc interval prolongation
    • Drugs are known to prolong the QTc interval
    • Avoid concomitant use
    • May increase the risk of QTc interval prolongation and related adverse reactions

Perform more frequent ECG monitoring if coadministered; hold for QTc interval above 480 msec and resume when QTc interval returns less than 480 msec

Pregnancy and Lactation

May cause fetal harm if administered during pregnancy, based on animal data and the mechanism of action

Data are not available in pregnant patients to evaluate for drug-associated risk

Advise pregnant patients of potential fetal risk

Perform pregnancy testing within 7 days of starting therapy in females of reproductive potential

Contraception requirements

• Effective contraception is recommended during therapy and for 4 months after the last dose in females of reproductive potential and males with female partners of reproductive potential

Infertility

• May impair fertility in males and females, based on animal data
• Effects may be reversible

Lactation

• Data are unavailable on presence of revumenib or its metabolites in human milk, its effects on breastfed children, or milk production
• Avoid breastfeeding during therapy and for 1 week after the last dose due to the risk of serious adverse effects in nursing children