REVUFORJ Film-coated tablet Ref.[116086] Active ingredients: Revumenib

2.1 Patient Selection

Relapsed or Refractory Acute Leukemia with a KMT2A Translocation

Select patients for treatment with REVUFORJ based on the presence of a KMT2A translocation [see Clinical Studies (14.1)]. Information on FDA authorized tests for the detection of a KMT2A translocation to determine eligibility for treatment is available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?id=DEN240067

Relapsed or Refractory Acute Myeloid Leukemia with an NPM1 mutation

Select patients for treatment with REVUFORJ based on the presence of an NPM1 mutation [see Clinical Pharmacology (12.1) and Clinical Studies (14.2)]. An FDA-approved companion diagnostic for the detection of an NPM1 mutation is not currently available.

2.2 Recommended Dosage

The recommended dosage of REVUFORJ varies by patient weight and concomitant use of strong CYP3A4 inhibitors. See Table 1 for the recommended dosage for patients 1 year and older. Do not start REVUFORJ until the WBC is reduced to less than 25 Gi/L. Continue REVUFORJ until disease progression or unacceptable toxicity. For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response.

Table 1. REVUFORJ Recommended Dosage for Patients 1 Year and Older:

^* See Table 2 for the total tablet dosage by BSA (body surface area) for patients weighing less than 40 kg.

Table 2. Recommended Dosage using Tablets* for Patients Weighing Less than 40 kg:

^* If needed, attain the desired dose by combining different strengths of REVUFORJ tablets.

• 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 (Table 1).
• Concurrent use of standard intrathecal chemotherapy prophylaxis is recommended for patients with risk of central nervous system relapse.

Administration:

• Correct hypokalemia, hypomagnesemia, and other electrolyte abnormalities prior to treatment.
• Administer REVUFORJ twice daily fasted or with a low-fat meal (e.g., meals with approximately 400 calories, 25% or less fat).
• Administer REVUFORJ orally around the same time each day.
• 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 [see Instructions for Use].
• 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.

2.3 Dosage Modifications for Adverse Reactions

Assess blood counts, electrolytes, and liver enzymes prior to the initiation of REVUFORJ and monthly thereafter. Perform an electrocardiogram (ECG) prior to the initiation of REVUFORJ, at least once a week for the first 4 weeks, and at least monthly thereafter. Monitor for QTc interval prolongation and manage any abnormalities promptly [see Warnings and Precautions (5.2) and Adverse Reactions (6.1)].

Interrupt dosing or reduce dose for adverse reactions as per Table 3. Dose levels for dose reductions are listed in Table 4, Table 5, and Table 6.

Table 3. Recommended Management and Dosage Modifications for Adverse Reactions:

^* 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 for the reduced dose levels.

Table 4. REVUFORJ Dosage Reduction for Adverse Reactions in Patients NOT on Strong CYP3A4 Inhibitors:

^** See Table 6 for BSA-based dosage recommendations for the reduced dosage of 95 mg/m² twice daily.

Table 5. REVUFORJ Dosage Reduction for Adverse Reactions in Patients on Strong CYP3A4 Inhibitors:

^* See Table 6 for BSA-based dosage recommendations for the reduced dosage of 65 mg/m² twice daily.

Table 6. Recommended Reduced Dosage Using Tablets* for Patients Weighing Less than 40 kg*:

^* If needed, attain the desired dose by combining different strengths of REVUFORJ tablets.

Store tablets at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Store and dispense in the orginal container.