Revuforj precisely blocks the interaction between KMT2A fusion protein and menin protein, inhibits abnormal activation of leukemia related genes (such as HOX and MEIS), blocks the proliferation pathway of leukemia cells, and provides a new targeted treatment option for patients with relapsed or refractory acute leukemia.

1、 Drug name

1. Common name: Revumenib

2. Product Name: REVUFORJ ®

2、 Indications

REVUFORJ is a menin inhibitor suitable for treating the following patients:

1. Recurrent or refractory acute leukemia with KMT2A gene translocation, suitable for adult and pediatric patients aged 1 year and above.

2. Recurrent or refractory acute myeloid leukemia with susceptible NPM1 mutations is suitable for adult and pediatric patients aged 1 year and above, and there are no other satisfactory alternative treatment options.

3、 Specifications and characteristics

This product is a film coated tablet, 160mg tablet: purple, modified oval shape, with "S" engraved on one side and "110" engraved on the other side.

4、 Main components

Active ingredient: Revumenib, present in the form of Revumenib citrate monohydrate.

5、 Usage and dosage

1. Patient selection: Before starting treatment, it is necessary to confirm the presence of KMT2A translocation or NPM1 mutation through FDA authorized testing.

2. Recommended dosage: The dosage is based on the patient's weight and whether a potent CYP3A4 inhibitor is used in combination.

Patients weighing ≥ 40kg:

1. Not combined with potent CYP3A4 inhibitor: 270mg, orally, twice daily.

2. Combination therapy with potent CYP3A4 inhibitor: 160mg, orally, twice daily.

3. Patients weighing less than 40kg: The dosage is calculated based on body surface area, and the specific dosage should follow the doctor's advice.

4. Administration method:

Timing: Take orally twice a day, approximately at the same time, on an empty stomach or with a low-fat meal.

Usage: Swallow the whole tablet, do not cut or chew. If it is not possible to swallow the entire tablet, the tablet can be crushed and dispersed in water for consumption. After preparation, it should be taken within 2 hours.

Omission treatment: If the medication is missed or not taken at the regular time, it should be taken as soon as possible on the same day, and it should be ensured that there is at least a 12 hour interval between the next scheduled administration time. The next day, the normal medication schedule will be resumed. Do not take two doses within 12 hours.

6、 Dose adjustment

Dose interruption, reduction or permanent discontinuation should be carried out according to the severity of adverse reactions. The main adjustments include:

1. Differentiation syndrome: If suspected, immediately begin systemic corticosteroid treatment and hemodynamic monitoring. If severe symptoms persist for more than 48 hours after starting corticosteroid treatment, or if life-threatening symptoms occur, REVUFORJ treatment should be discontinued.

2. QTc interval prolongation:

QTc>480 to 500msec: Discontinue administration, correct electrolyte abnormalities, and restart at the original dose after QTc returns to ≤ 480sec.

QTc>500msec: Discontinue administration, correct electrolyte abnormalities, and restart at a reduced dose after QTc returns to ≤ 480sec.

Symptoms of life-threatening arrhythmia: permanent discontinuation of medication.

3. Other adverse reactions: For non hematological adverse reactions of grade ≥ 3, grade 4 neutropenia or thrombocytopenia, there are corresponding plans to interrupt administration, reduce dosage, or permanently discontinue medication. Please refer to the dosage table in the drug manual for specific dosage reductions.

7、 Medication precautions

1. Before/after meals: can be taken on an empty stomach or with a low-fat meal.

2. Leakage: Please refer to the "Usage and Dosage" section for the handling method.

3. Vomiting: If vomiting occurs after taking medication or if the full dose is not swallowed, it should not be taken again and should be waited until the next scheduled administration time.

4. Important monitoring:

Before treatment, the white blood cell count should be reduced to<25Gi/L.

Hypokalemia, hypomagnesemia, and other electrolyte abnormalities should be corrected before and during treatment.

Perform electrocardiogram monitoring at least once a week before treatment, for the first 4 weeks of treatment, and at least once a month thereafter.

Monitor blood cell count, electrolytes, and liver enzymes before treatment and monthly.

8、 Medication for special populations

1. Pregnant women: Based on animal data and mechanism of action, this product may cause fetal harm. Pregnant women should be informed of potential risks to the fetus.

2. Breastfeeding women: It is recommended not to breastfeed during the treatment period and within one week after the last dose.

3. Women and men with reproductive potential:

Women need to undergo pregnancy testing 7 days before starting treatment.

Effective contraceptive measures should be taken by both women and men during the treatment period and 4 months after the last dose.

Based on animal data, this product may impair fertility.

4. Pediatric medication: The safety and efficacy of medication for children aged 1 year and above have been established. The safety and effectiveness of children under 1 year old have not yet been established. For children weighing less than 40kg, the dosage should be adjusted according to the body surface area. Need to monitor bone growth and development.

5. Medication for the elderly: The incidence of QTc prolongation and edema is higher in patients aged 65 and above.

9、 Adverse reactions

1. Serious adverse reactions:

Differentiation syndrome (can be fatal).

QTc interval prolongation and apical torsion type ventricular tachycardia (fatal).

Embryo fetal toxicity.

2. Common adverse reactions: Adverse reactions with an incidence rate of ≥ 20% include elevated blood phosphate, bleeding, nausea, infection with unknown pathogen, elevated aspartate aminotransferase, elevated alanine aminotransferase, elevated creatinine, musculoskeletal pain, febrile neutropenia, prolonged QT on electrocardiogram, decreased blood potassium, elevated parathyroid hormone, elevated alkaline phosphatase, diarrhea, bacterial infection, elevated triglycerides, differentiation syndrome, fatigue, edema, viral infection, decreased blood phosphate, decreased appetite, and constipation.

10、 Contraindications

None.

11、 Drug interactions

1. Strong CYP3A4 inhibitor: If combined use is required, reduce the dosage of REVUFORJ.

2. Strong or moderate CYP3A4 inducers: Avoid combination use.

3. Medications that prolong QTc interval: avoid combination therapy. If unavoidable, it is necessary to monitor the patient's QTc interval more frequently.

12、 Storage method

1. Stored at 20 ° C to 25 ° C, allowing for short distance transportation between 15 ° C and 30 ° C.

2. Store and distribute in original containers.

3. The medicine bottle contains desiccants and child proof bottle caps.

13、 Manufacturer

Manufacturer: SyndaxPharmaceuticals, Inc

Revuforjinformation