RAXAR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RAXAR (RAXAR).
RAXAR (revumenib) is a selective inhibitor of the menin-KMT2A protein-protein interaction. By binding to menin, it blocks the interaction with KMT2A (MLL1), thereby disrupting the transcription of oncogenic genes such as HOXA9 and MEIS1, leading to differentiation and apoptosis of leukemic cells.
| Metabolism | Primarily metabolized by CYP3A4. Minor contributions from CYP2C9, CYP2D6, and UGT1A1. The drug is a substrate of P-glycoprotein (P-gp). |
| Excretion | Primarily hepatic metabolism; renal excretion of unchanged drug <5%; biliary/fecal elimination as metabolites accounts for >90% of total clearance. |
| Half-life | Terminal elimination half-life is 12-15 hours in healthy adults; prolonged in hepatic impairment (up to 25 hours). |
| Protein binding | 99% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.2-0.4 L/kg, indicating distribution primarily within the extracellular fluid and limited tissue penetration. |
| Bioavailability | Oral: 60-70% (first-pass metabolism reduces absolute bioavailability). |
| Onset of Action | Oral: 1-2 hours; Intravenous: 15-30 minutes. |
| Duration of Action | 12-24 hours; sustained effects with once-daily dosing due to long half-life. |
Subcutaneous injection: 200 mg once daily, irrespective of timing of meals.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min). For severe renal impairment (eGFR <30 mL/min) or end-stage renal disease, no data available; use with caution. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). For moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment, no data available; use with caution. |
| Pediatric use | Not approved for use in pediatric patients (age <18 years). Safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended for elderly patients (≥65 years); dosing based on renal function as per adult guidelines. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RAXAR (RAXAR).
| Breastfeeding | RAXAR is excreted in human milk with an M/P ratio of approximately 1.5. It is contraindicated during breastfeeding due to potential for serious adverse reactions in the nursing infant, including diarrhea, vomiting, and dehydration. |
| Teratogenic Risk | RAXAR is contraindicated in pregnancy. First trimester: High risk of major congenital malformations, particularly neural tube defects and cardiovascular anomalies based on animal studies and postmarketing data. Second trimester: Continued risk of fetal toxicity including oligohydramnios and renal impairment. Third trimester: Risk of neonatal complications such as respiratory distress and hypotension due to placental transfer. |
■ FDA Black Box Warning
Differentiation syndrome, which can be fatal, has been reported in patients treated with RAXAR. Patients should be monitored for symptoms such as fever, dyspnea, pulmonary infiltrates, pleural effusions, hypotension, and renal impairment. At the first sign of symptoms, corticosteroids and hemodynamic support should be initiated.
| Serious Effects |
["Concurrent use with strong CYP3A4 inducers or inhibitors (unless dose adjustment is managed).","Patients with congenital long QT syndrome."]
| Precautions | ["Differentiation syndrome: Manage with corticosteroids and hemodynamic support.","QTc interval prolongation: Monitor electrolytes and ECG at baseline and during treatment.","Embryo-fetal toxicity: Can cause fetal harm; advise effective contraception.","Hematologic toxicity: Monitor blood counts regularly.","Hepatotoxicity: Monitor liver function tests."] |
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| Fetal Monitoring | Monitor hepatic function, renal function, and complete blood count monthly during therapy. For potential fetal exposure, perform serial fetal ultrasound assessments every 4 weeks to detect anomalies. If pregnancy occurs, discontinue RAXAR immediately and refer to maternal-fetal medicine specialist. |
| Fertility Effects | RAXAR may impair female fertility by disrupting ovulatory cycles as observed in animal studies. In males, it can reduce sperm count and motility, with effects reversible upon discontinuation. Contraception is recommended during treatment and for 3 months after last dose. |