Instructions for Revuforj (Revumenib)

1. Name:Revumenib

Product name:Revuforj

2. Indications:

Revuforj (Revumenib) is indicated for the treatment of relapsed or refractory (R/R) acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adults and children 1 year of age and older.

3. Usage and dosage:

1. Patient selection: Acute leukemia patients who receive Revuforj treatment are selected based on the presence ofKMT2A translocation in bone marrow cells. There are currently no FDA-approved companion diagnostics for the detection of KMT2A translocations.

2. Recommended dose:The recommended dose of Revuforj varies based on patient weight and concurrent use of strong CYP3A4 inhibitors. Do not start taking Revuforj until your white blood cells have dropped below 25 Gi/L. Continue taking Revuforj until disease progression or unacceptable toxicity occurs. For patients without disease progression or unacceptable toxicity, treat for at least 6 months to allow time to achieve clinical response.

The starting dose for patients weighing 40 kg or more is 270 mg orally twice daily; for patients weighing less than 40 kg, the starting dose is 160 mg/m3 orally twice daily; recommended dose for patients 1 year and older Follow your doctor's advice.

3. Medication management: Patients need to take Revuforj twice a day without food or with a low-fat meal (for example, a meal containing approximately 400 calories and 25% or less fat). Take by mouth at approximately the same time each day. Patients are advised to swallow the tablets whole and not to cut or chew the tablets. If the patient is unable to swallow the tablets, they can be crushed and dispersed in water and taken within 2 hours of preparation. If a dose of Revuforj is missed or not taken at the usual time, the dose should be taken as soon as possible on the same day and at least 12 hours before the next scheduled dose. Back to normal schedule the next day. Do not take 2 doses within 12 hours.

4. Dosage adjustment: Assess blood cell counts, electrolytes, and liver enzymes before starting Revuforj and monthly thereafter. Before starting Revuforj, perform an EKG at least once a week (for the first 4 weeks) and at least once a month thereafter. Monitor for QTc interval prolongation and promptly address any abnormalities.

4. Adverse reactions:

In Revuforj’s clinical studies, the most common (≥20%) adverse reactions include bleeding, nausea, increased phosphate, musculoskeletal pain, infection, increased aspartate aminotransferase, febrile neutropenia, increased alanine aminotransferase, increased parathyroid hormone integrity, bacterial infection, diarrhea, differentiation syndrome, electrocardiogram QT prolongation, decreased phosphate, increased triglycerides, decreased potassium, decreased appetite, constipation, edema, viral infection, fatigue, and increased alkaline phosphatase.

5. Supply and storage:

Revuforjis a tablet containing25mg, 110mg, 160mg, kept in the original container before dispensing. , store at 20°C to 25°C (68°F to 77°F); tolerances allowed between 15°C to 30°C (59°F to 86°F).

6. Special groups:

1. Women: According to animal research results and its mechanism of action, pregnant women taking Revuforj may cause harm to the fetus. Therefore verify the pregnancy status of women of reproductive potential within 7 days before startingRevuforj; recommend that women of reproductive potential use effective contraception during treatment with the drug and for 4 months after the last dose; advise women not to breastfeed during treatment with the drug and within 1 week after the last dose.

2. Men: Based on animal studies, Revuforj may impair fertility; therefore, it is recommended that men of reproductive potential use effective contraception during drug treatment and for 4 months after the last dose.

7. Mechanism of action:

Revuforj's main ingredient, Revumenib, is a menin inhibitor that blocks the interaction of wild-type lysine methyltransferase 2A (KMT2A) and KMT2A fusion proteins with menin. The binding of KMT2A fusion protein to menin is involved in KMT2A rearrangement (KMT2Ar) acute leukemia by activating the leukemogenic transcription pathway. In nonclinical studies using cells expressing the KMT2A fusion, 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 containing the KMT2A fusion protein.

Reference materials:https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6eb3cdbc-0e74-477d-82d6-3bb172d3f63f