Revuforj

2 DOSAGE AND ADMINISTRATION Select patients for treatment with REVUFORJ based on the presence of a KMT2A translocation or an NPM1 mutation. ( 2.1 ) Administer REVUFORJ orally twice daily fasted or with a low-fat meal at approximately the same time each day. ( 2.2 ) See Full Prescribing Information for recommended REVUFORJ dosage regimen, dosage modifications, and administration instructions. ( 2.2 , 2.3 ) 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. Patient Weight Without Strong CYP3A4 Inhibitors With Strong CYP3A4 Inhibitors 40 kg or more 270 mg orally twice daily 160 mg orally twice daily Less than 40 kg 160 mg/m 2 orally twice daily* 95 mg/m 2 orally twice daily* 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. BSA (m 2 ) REVUFORJ Dosage for 160 mg/m 2 REVUFORJ Dosage for 95 mg/m 2 1.4 220 mg twice daily 135 mg twice daily 1.3 220 mg twice daily 135 mg twice daily 1.2 185 mg twice daily 110 mg twice daily 1.1 185 mg twice daily 110 mg twice daily 1 160 mg twice daily 100 mg twice daily 0.9 135 mg twice daily 75 mg twice daily 0.8 135 mg twice daily 75 mg twice daily 0.7 110 mg twice daily 50 mg twice daily 0.6 100 mg twice daily 50 mg twice daily 0.5 75 mg twice daily 50 mg twice daily 0.4 50 mg twice daily 25 mg twice daily 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. Adverse reaction Recommended action Differentiation Syndrome [see Warnings and Precautions (5.1) ] If differentiation syndrome is suspected, administer systemic corticosteroids and initiate hemodynamic monitoring until symptom resolution and for a minimum of 3 days. [see Warnings and Precautions (5.1) ] . Interrupt REVUFORJ if severe signs and/or symptoms persist for more than 48 hours after initiation of systemic corticosteroids, or earlier for life-threatening symptoms such as pulmonary symptoms requiring ventilator support [see Warnings and Precautions (5.1) ] . Resume REVUFORJ at the same dose when signs and symptoms improve to Grade 1* or lower. Noninfectious leukocytosis Initiate treatment with hydroxyurea in patients with an elevated or rapidly rising leukocyte count. Add leukapheresis if clinically indicated. Taper hydroxyurea only after leukocytosis improves or resolves. QTc interval greater than 480 msec to 500 msec [see Warnings and Precautions(5.2) ] Interrupt REVUFORJ. Check electrolyte levels. Correct hypokalemia and hypomagnesemia [see Warnings and Precautions (5.2) ] . Restart REVUFORJ at the same dose level after the QTc interval returns to less than or equal to 480 msec. QTc interval greater than 500 msec (Grade 3*) [see Warnings and Precautions (5.2) ] Interrupt REVUFORJ. Check electrolyte levels. Correct hypokalemia and hypomagnesemia [see Warnings and Precautions (5.2) ] . Restart REVUFORJ at the reduced dose level** after the QTc interval returns to less than or equal to 480 msec. QTc interval prolongation with signs/symptoms of life-threatening arrhythmia, Torsades de pointes, polymorphic ventricular tachycardia, signs/ symptoms of life-threatening arrhythmia (Grade 4*) [see Warnings and Precautions (5.2) ] . Permanently discontinue REVUFORJ. Potassium 3.6-3.9 mEq/L, and/or Magnesium 1.7-1.9 mg/dL or 0.66-0.81 mmol/L Supplement potassium and/or magnesium. Continue REVUFORJ. Potassium ≤ 3.5 mEq/L, and/or Magnesium ≤ 1.6 mg/dL or ≤ 0.65 mmol/L Supplement potassium and/or magnesium, and recheck levels within 24 hours. On recheck of potassium and magnesium labs within 24 hours, if potassium is greater than 3.5 mEq/L and/or magnesium is greater than 1.6 mg/dL, continue REVUFORJ. If potassium is less than 3.5 mEq/L and/or magnesium is less than 1.6 mg/dL, hold REVUFORJ and continue supplementation; resume REVUFORJ at the same dose level when the correction is complete. Other nonhematological adverse reactions Grade ≥ 3* [see Adverse Reactions (6.1) ] Interrupt REVUFORJ until recovery to Grade 1* or baseline. If recovered in ≤ 7 days, restart REVUFORJ at the same dose level. If the same Grade ≥ 3* toxicity recurs, interrupt REVUFORJ until recovery to Grade 1* or baseline. Restart REVUFORJ at the reduced dose level.** If recovered in > 7 days, restart REVUFORJ at the reduced dose level.** If the same Grade ≥ 3* toxicity recurs, discontinue REVUFORJ. Grade 4* neutropenia or thrombocytopenia [see Adverse Reactions (6.1) ] Interrupt REVUFORJ until recovery to Grade ≤ 2* or baseline. Restart REVUFORJ at the same dose level. If Grade 4* neutropenia or thrombocytopenia recurs without attributable cause, interrupt REVUFORJ until recovery to Grade ≤ 3*. Restart REVUFORJ at the reduced dose level.** Grade 3* or higher allergic reactions [see Adverse Reactions (6.1) ] Permanently discontinue REVUFORJ. 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/m 2 twice daily. Patients Weighing 40 kg or Greater at Starting Dose 270 mg orally twice daily Patients Weighing Less Than 40 kg at Starting Dose 160 mg/m 2 orally twice daily Reduced Dose 160 mg orally twice daily 95 mg/m 2 orally 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/m 2 twice daily. Patients Weighing 40 kg or Greater at Starting Dose 160 mg orally twice daily Patients Weighing Less Than 40 kg at Starting Dose 95 mg/m 2 orally twice daily Reduced Dose 110 mg orally twice daily 65 mg/m 2 orally 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. BSA (m 2 ) REVUFORJ Dosage for 95 mg/m 2 REVUFORJ Dosage for 65 mg/m 2 1.4 135 mg twice daily 100 mg twice daily 1.3 135 mg twice daily 75 mg twice daily 1.2 110 mg twice daily 75 mg twice daily 1.1 110 mg twice daily 75 mg twice daily 1 100 mg twice daily 50 mg twice daily 0.9 75 mg twice daily 50 mg twice daily 0.8 75 mg twice daily 50 mg twice daily 0.7 50 mg twice daily 50 mg twice daily 0.6 50 mg twice daily 25 mg twice daily 0.5 50 mg twice daily 25 mg twice daily 0.4 25 mg twice daily 25 mg twice daily

See official label

1 INDICATIONS AND USAGE REVUFORJ is a menin inhibitor indicated for: the treatment of 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 1 year and older.