VYXEOS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VYXEOS (VYXEOS).

How it works

Daunorubicin and cytarabine are both antineoplastic agents. Daunorubicin intercalates with DNA, inhibits topoisomerase II, and generates free radicals leading to DNA damage and cell death. Cytarabine is a nucleoside analog that inhibits DNA polymerase by competing with cytidine triphosphate, incorporating into DNA and RNA, and causing chain termination.

What the body does with it

Metabolism	Daunorubicin is metabolized via aldo-keto reductases to daunorubicinol, which is active. Cytarabine is primarily metabolized by cytidine deaminase to inactive uracil arabinoside (ara-U).
Excretion	Primarily hepatobiliary excretion; 70-80% of dose recovered in feces as metabolites, less than 10% in urine as unchanged liposomal daunorubicin and cytarabine.
Half-life	Daunorubicin: terminal half-life approximately 56 h; cytarabine: terminal half-life approximately 31 h. The prolonged half-lives reflect sustained release from liposomes, allowing continuous exposure.
Protein binding	Daunorubicin: approximately 60-70% bound to albumin and tissue proteins; cytarabine: approximately 15% bound to albumin.
Volume of Distribution	Daunorubicin: Vd approximately 0.5-1 L/kg, indicating extensive tissue distribution; cytarabine: Vd approximately 0.3-0.5 L/kg, distributed mainly in total body water.
Bioavailability	Not applicable (IV only); oral bioavailability not established for liposomal formulation.
Onset of Action	IV infusion: antileukemic effect begins within days, with cytoreduction noted as early as 24-48 hours post-infusion.
Duration of Action	The liposomal formulation extends duration of cytotoxic concentrations; daunorubicin and cytarabine remain detectable in plasma for >7 days. Clinical effect persists through the treatment cycle.

Classification & Brands

Dosing & administration

Each unit contains 44 mg daunorubicin and 100 mg cytarabine. Adults: 1 unit/m² IV over 90 minutes on days 1, 3, and 5 for induction; up to 2 cycles. For consolidation: 1 unit/m² IV over 90 minutes on days 1 and 3; up to 2 cycles.

Dosage form	POWDER
Renal impairment	Contraindicated in severe renal impairment (CrCl < 30 mL/min). For CrCl 30-60 mL/min: reduce dose by 25%. Monitor renal function.
Liver impairment	Contraindicated in severe hepatic impairment (Child-Pugh C). For Child-Pugh B: reduce dose by 50%. For Child-Pugh A: no adjustment needed.
Pediatric use	Safety and efficacy not established. No standard pediatric dosing. Use only in clinical trials.
Geriatric use	No specific dose adjustment based on age alone. Monitor renal and hepatic function; consider dose reduction in frail elderly patients due to increased toxicity risk.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for VYXEOS (VYXEOS).

Breastfeeding	Not recommended. It is unknown if excreted into human milk. M/P ratio not available. Advise to discontinue breastfeeding during treatment and for at least 1 month after last dose due to potential for serious adverse reactions in breastfed infants.
Teratogenic Risk	VYXEOS (daunorubicin and cytarabine liposome) is contraindicated in pregnancy. It is embryotoxic and fetotoxic in animals. First trimester: high risk of major malformations (neural tube, cardiac). Second/third trimester: risk of fetal growth restriction, preterm birth, and neonatal myelosuppression. Use effective contraception.

Warnings & precautions

■ FDA Black Box Warning

WARNING: DAUNORUBICIN IS A CARDIOTOXIC AGENT. DAUNORUBICIN CAN CAUSE MYELOSUPPRESSION AND SEVERE BLEEDING. VYXEOS IS A LIPOSOMAL FORMULATION; DO NOT SUBSTITUTE FOR OTHER DAUNORUBICIN OR CYTARABINE PRODUCTS.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to daunorubicin, cytarabine, or any component of the formulation.","History of serious hypersensitivity reactions to any conventional daunorubicin or cytarabine product."]

Clinical Precautions

Precautions

["Cardiotoxicity: Left ventricular dysfunction, especially with cumulative doses; monitor cardiac function.","Myelosuppression: Severe, can lead to fatal infections or bleeding.","Hemorrhage: Fatal hemorrhages reported.","Tumor lysis syndrome: Risk due to rapid lysis.","Hepatotoxicity: Elevations in bilirubin and transaminases.","Embryo-fetal toxicity: Can cause fetal harm; advise effective contraception."]

Clinical Tips & Counseling

Drug interactions

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VYXEOS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VYXEOS (VYXEOS).

How it works

What the body does with it

Metabolism	Daunorubicin is metabolized via aldo-keto reductases to daunorubicinol, which is active. Cytarabine is primarily metabolized by cytidine deaminase to inactive uracil arabinoside (ara-U).
Excretion	Primarily hepatobiliary excretion; 70-80% of dose recovered in feces as metabolites, less than 10% in urine as unchanged liposomal daunorubicin and cytarabine.
Half-life	Daunorubicin: terminal half-life approximately 56 h; cytarabine: terminal half-life approximately 31 h. The prolonged half-lives reflect sustained release from liposomes, allowing continuous exposure.
Protein binding	Daunorubicin: approximately 60-70% bound to albumin and tissue proteins; cytarabine: approximately 15% bound to albumin.
Volume of Distribution	Daunorubicin: Vd approximately 0.5-1 L/kg, indicating extensive tissue distribution; cytarabine: Vd approximately 0.3-0.5 L/kg, distributed mainly in total body water.
Bioavailability	Not applicable (IV only); oral bioavailability not established for liposomal formulation.
Onset of Action	IV infusion: antileukemic effect begins within days, with cytoreduction noted as early as 24-48 hours post-infusion.
Duration of Action	The liposomal formulation extends duration of cytotoxic concentrations; daunorubicin and cytarabine remain detectable in plasma for >7 days. Clinical effect persists through the treatment cycle.

Classification & Brands

Dosing & administration

Dosage form	POWDER
Renal impairment	Contraindicated in severe renal impairment (CrCl < 30 mL/min). For CrCl 30-60 mL/min: reduce dose by 25%. Monitor renal function.
Liver impairment	Contraindicated in severe hepatic impairment (Child-Pugh C). For Child-Pugh B: reduce dose by 50%. For Child-Pugh A: no adjustment needed.
Pediatric use	Safety and efficacy not established. No standard pediatric dosing. Use only in clinical trials.
Geriatric use	No specific dose adjustment based on age alone. Monitor renal and hepatic function; consider dose reduction in frail elderly patients due to increased toxicity risk.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for VYXEOS (VYXEOS).

Breastfeeding	Not recommended. It is unknown if excreted into human milk. M/P ratio not available. Advise to discontinue breastfeeding during treatment and for at least 1 month after last dose due to potential for serious adverse reactions in breastfed infants.
Teratogenic Risk	VYXEOS (daunorubicin and cytarabine liposome) is contraindicated in pregnancy. It is embryotoxic and fetotoxic in animals. First trimester: high risk of major malformations (neural tube, cardiac). Second/third trimester: risk of fetal growth restriction, preterm birth, and neonatal myelosuppression. Use effective contraception.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to daunorubicin, cytarabine, or any component of the formulation.","History of serious hypersensitivity reactions to any conventional daunorubicin or cytarabine product."]