REVUFORJ

Clinical safety rating: caution

Comprehensive clinical and safety monograph for REVUFORJ (REVUFORJ).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for REVUFORJ (REVUFORJ).

Breastfeeding	Contraindicated during breastfeeding. M/P ratio not determined; drug excreted in human milk in levels that may cause adverse effects in the infant. Avoid breastfeeding for at least 48 hours after last dose.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Concomitant use with strong or moderate CYP3A4 inducers","Concomitant use with sensitive CYP3A4 substrates (e.g., midazolam) due to potential for reduced efficacy","Known hypersensitivity to revumenib or any excipients"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

REVUFORJ

Clinical safety rating: caution

Comprehensive clinical and safety monograph for REVUFORJ (REVUFORJ).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for REVUFORJ (REVUFORJ).

Breastfeeding	Contraindicated during breastfeeding. M/P ratio not determined; drug excreted in human milk in levels that may cause adverse effects in the infant. Avoid breastfeeding for at least 48 hours after last dose.
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.

Warnings & precautions

■ 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.