REVUFORJ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REVUFORJ (REVUFORJ).
REVUFORJ (revumenib) is a potent and selective oral inhibitor of the menin-KMT2A (MLL) protein-protein interaction. It blocks the binding of menin to the N-terminus of KMT2A fusion proteins and mutant NPM1, thereby inhibiting the transcriptional activation of downstream target genes (e.g., HOXA9, MEIS1) that drive leukemogenesis.
| Metabolism | Primarily metabolized by CYP3A4 and UGT1A3 |
| Excretion | Primarily renal excretion of unchanged drug (approximately 70%) and fecal excretion (approximately 20%) via biliary elimination; minimal metabolism. |
| Half-life | Terminal elimination half-life is approximately 40 hours in healthy subjects; extended to 72 hours in patients with moderate hepatic impairment (Child-Pugh B), requiring dose adjustment. |
| Protein binding | Approximately 85% bound to plasma proteins, primarily albumin and alpha-1 acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 1.2 L/kg, indicating extensive extravascular distribution and tissue penetration. |
| Bioavailability | Oral bioavailability is 75% under fed conditions (increased by high-fat meal) and 60% under fasting conditions; food effect is clinically significant. |
| Onset of Action | Oral administration: clinical effect observed within 2-3 hours; maximum effect achieved by 4-6 hours. |
| Duration of Action | Duration of action is approximately 24 hours with once-daily dosing; sustained viral suppression maintained for up to 48 hours post last dose. |
| Molecular Weight | 390.46 |
Oral, 500 mg twice daily.
| Dosage form | TABLET |
| Renal impairment | eGFR 30-59 mL/min: 250 mg twice daily; eGFR <30 mL/min: 250 mg once daily; on dialysis: 250 mg three times weekly post-dialysis. |
| Liver impairment | Child-Pugh class A: no adjustment; Child-Pugh class B: reduce dose by 50%; Child-Pugh class C: not recommended. |
| Pediatric use | Not established for patients <18 years. |
| Geriatric use | Start at lowest dose; monitor renal function; adjust per renal guidelines. |
| 1st trimester | Contraindicated due to risk of fetal malformations based on animal studies and its mechanism of action (spermatogenesis inhibitor for men; no human pregnancy data, but theoretical risk). |
| 2nd trimester | Contraindicated due to potential fetal harm from antiandrogenic effects; no human data, but animal studies show adverse outcomes. |
| 3rd trimester | Contraindicated due to risk of fetal androgen deprivation and potential teratogenicity. |
Clinical note
Comprehensive clinical and safety monograph for REVUFORJ (REVUFORJ).
| Placental transfer | Likely crosses placenta based on molecular weight and lipophilicity; no human studies available, but animal studies indicate transfer. |
| Breastfeeding | Excretion into human milk unknown; due to potential for serious adverse effects in nursing infants, avoid breastfeeding during treatment and for at least 2 weeks after last dose. |
■ FDA Black Box Warning
Differentiation syndrome, which can be fatal, has been reported. If differentiation syndrome is suspected, discontinue REVUFORJ, administer corticosteroids, and monitor hemodynamics.
| Serious Effects |
PregnancyWomen of childbearing potential not using effective contraception
| Precautions | Differentiation syndrome: can be fatal; early recognition and intervention required, QTc interval prolongation: monitor electrocardiograms and electrolytes; avoid use with other drugs that prolong QTc, Embryo-fetal toxicity: can cause fetal harm; advise females and males of reproductive potential to use effective contraception |
| Food/Dietary | Avoid grapefruit and star fruit due to CYP3A4 inhibition potential. Take with or without food; no specific food restrictions. |
Loading safety data…
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | First trimester: Increased risk of congenital malformations, particularly neural tube defects and cardiac anomalies. Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and fetal renal impairment. Late third trimester: Risk of preterm labor and neonatal respiratory distress. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function (serum creatinine, BUN), and liver enzymes every 2 weeks. Fetal ultrasound every 4 weeks for growth and amniotic fluid volume. Non-stress test or biophysical profile weekly after 32 weeks. Monitor for signs of preeclampsia. |
| Fertility Effects | Animal studies indicate impaired fertility with reduced implantation rates and ovarian dysfunction. Human data limited; may cause reversible menstrual irregularities and anovulation. Advise effective contraception during treatment. |
| Clinical Pearls | REVUFORJ (danicopan) is a complement factor D inhibitor used for paroxysmal nocturnal hemoglobinuria (PNH). Monitor for hemolysis, thrombosis, and breakthrough disease. Discontinue 2 weeks prior to surgery to reduce bleeding risk. Dose adjustment needed for hepatic impairment. Not recommended with strong CYP3A4 inducers. |
| Patient Advice | Take exactly as prescribed; do not miss doses to prevent hemolysis. · Report any signs of hemolysis (dark urine, jaundice, fatigue, shortness of breath) or thrombosis (chest pain, leg swelling). · Avoid live vaccines during treatment. · Inform all healthcare providers of REVUFORJ use, especially before surgery or procedures. · Do not stop abruptly; consult doctor for discontinuation plan. |