CYTARABINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CYTARABINE (CYTARABINE).

How it works

Cytarabine is a pyrimidine nucleoside analog that inhibits DNA synthesis. It is converted intracellularly to its active triphosphate form, which competes with deoxycytidine triphosphate for incorporation into DNA, leading to chain termination and inhibition of DNA polymerase. It also inhibits DNA repair and RNA synthesis.

What the body does with it

Metabolism	Primarily deaminated by cytidine deaminase in the liver and kidney to the inactive metabolite uracil arabinoside. Also phosphorylated intracellularly to active triphosphate.
Excretion	Primarily hepatic metabolism (deaminated by cytidine deaminase to inactive uracil arabinoside); renal excretion of unchanged drug accounts for <10% of dose; <1% biliary/fecal.
Half-life	Initial distribution half-life ~10 min; terminal elimination half-life ~1-3 hours (biphasic); prolongs in renal impairment.
Protein binding	Low (~13%), binds primarily to albumin.
Volume of Distribution	Vd ~0.75 L/kg (range 0.5-1.0 L/kg), indicating distribution into total body water; penetrates CSF (CSF:plasma ratio ~0.5).
Bioavailability	Subcutaneous: ~80-100%; oral: <20% (not clinically used).
Onset of Action	IV: Rapid (within minutes); intrathecal: ~15-30 min; subcutaneous: ~1-2 hours.
Duration of Action	IV: Cytotoxic levels persist for ~8-24 hours; intrathecal: effects last ~24-48 hours; requires continuous infusion or high doses for cell-cycle specific activity.

Classification & Brands

Action Class	Antimetabolites
Brand Substitutes	Cytaneon 1000mg Injection, Cytarine 1000mg Injection, Oncotar 1000mg Injection, Cytraz 1000mg Injection, Cytraze 1000mg Injection

Dosing & administration

100-200 mg/m² IV continuous infusion over 24 hours for 7 days (induction) or 1-3 g/m² IV every 12 hours for 3-6 days (high-dose). Intrathecal: 30-100 mg/m² (max 100 mg) once every 2-7 days.

Dosage form	INJECTABLE
Renal impairment	For CrCl 30-60 mL/min: reduce dose by 50% and monitor neurotoxicity. For CrCl <30 mL/min: administer 50% of dose and extend interval to every 24-48 hours. Hemodialysis: administer after dialysis, dose as per CrCl <30.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 25-50%. Child-Pugh C: avoid use; if necessary, reduce dose by 50% and monitor closely.
Pediatric use	Induction: 100-200 mg/m²/day IV continuous infusion for 5-7 days. High-dose: 1-3 g/m² IV every 12 hours for 3-6 doses. Intrathecal: age-based: <1 year 20 mg, 1-2 years 30 mg, 2-3 years 50 mg, >3 years 70-100 mg.
Geriatric use	Use lower end of dosing range due to increased myelosuppression and neurotoxicity. Start at 100 mg/m²/day for induction; monitor renal function. For high-dose, consider dose reduction to 1 g/m² every 12 hours.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for CYTARABINE (CYTARABINE).

Breastfeeding	Cytarabine is excreted into human milk. The milk-to-plasma (M/P) ratio is approximately 0.1-0.5. Due to potential for severe adverse effects (e.g., myelosuppression, immunosuppression) in the nursing infant, breastfeeding is contraindicated during therapy and for at least 48 hours after the last dose.
Teratogenic Risk	Cytarabine is embryotoxic and teratogenic in animals. In humans, first-trimester exposure is associated with an increased risk of congenital malformations, including skeletal and central nervous system anomalies. Second and third trimester use may cause fetal growth restriction, myelosuppression, and neonatal pancytopenia. Risk is dose-dependent and increased with combination chemotherapy.

Warnings & precautions

■ FDA Black Box Warning

Severe myelosuppression with prolonged pancytopenia, increased risk of infection and bleeding. High doses can cause severe cerebellar toxicity, including ataxia, dysarthria, and nystagmus. Intrathecal administration may cause neurotoxicity including seizures and myelopathy.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to cytarabine or any component of the formulation. Not recommended for use in patients with severe hepatic or renal impairment unless benefits outweigh risks. Intrathecal administration is contraindicated in patients with active central nervous system infection or bleeding.

Clinical Precautions

Precautions

May cause severe bone marrow suppression, requiring close monitoring of blood counts. High-dose therapy is associated with cerebellar toxicity, especially in patients >50 years, renal impairment, or prior neurotoxicity. Hepatic dysfunction may occur. Pancreatitis has been reported. Acute pulmonary edema and cardiomyopathy have occurred with high doses. Tumor lysis syndrome may occur.

Clinical Tips & Counseling

Drug interactions

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CYTARABINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CYTARABINE (CYTARABINE).

How it works

What the body does with it

Metabolism	Primarily deaminated by cytidine deaminase in the liver and kidney to the inactive metabolite uracil arabinoside. Also phosphorylated intracellularly to active triphosphate.
Excretion	Primarily hepatic metabolism (deaminated by cytidine deaminase to inactive uracil arabinoside); renal excretion of unchanged drug accounts for <10% of dose; <1% biliary/fecal.
Half-life	Initial distribution half-life ~10 min; terminal elimination half-life ~1-3 hours (biphasic); prolongs in renal impairment.
Protein binding	Low (~13%), binds primarily to albumin.
Volume of Distribution	Vd ~0.75 L/kg (range 0.5-1.0 L/kg), indicating distribution into total body water; penetrates CSF (CSF:plasma ratio ~0.5).
Bioavailability	Subcutaneous: ~80-100%; oral: <20% (not clinically used).
Onset of Action	IV: Rapid (within minutes); intrathecal: ~15-30 min; subcutaneous: ~1-2 hours.
Duration of Action	IV: Cytotoxic levels persist for ~8-24 hours; intrathecal: effects last ~24-48 hours; requires continuous infusion or high doses for cell-cycle specific activity.

Classification & Brands

Action Class	Antimetabolites
Brand Substitutes	Cytaneon 1000mg Injection, Cytarine 1000mg Injection, Oncotar 1000mg Injection, Cytraz 1000mg Injection, Cytraze 1000mg Injection

Dosing & administration

100-200 mg/m² IV continuous infusion over 24 hours for 7 days (induction) or 1-3 g/m² IV every 12 hours for 3-6 days (high-dose). Intrathecal: 30-100 mg/m² (max 100 mg) once every 2-7 days.

Dosage form	INJECTABLE
Renal impairment	For CrCl 30-60 mL/min: reduce dose by 50% and monitor neurotoxicity. For CrCl <30 mL/min: administer 50% of dose and extend interval to every 24-48 hours. Hemodialysis: administer after dialysis, dose as per CrCl <30.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 25-50%. Child-Pugh C: avoid use; if necessary, reduce dose by 50% and monitor closely.
Pediatric use	Induction: 100-200 mg/m²/day IV continuous infusion for 5-7 days. High-dose: 1-3 g/m² IV every 12 hours for 3-6 doses. Intrathecal: age-based: <1 year 20 mg, 1-2 years 30 mg, 2-3 years 50 mg, >3 years 70-100 mg.
Geriatric use	Use lower end of dosing range due to increased myelosuppression and neurotoxicity. Start at 100 mg/m²/day for induction; monitor renal function. For high-dose, consider dose reduction to 1 g/m² every 12 hours.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for CYTARABINE (CYTARABINE).

Breastfeeding	Cytarabine is excreted into human milk. The milk-to-plasma (M/P) ratio is approximately 0.1-0.5. Due to potential for severe adverse effects (e.g., myelosuppression, immunosuppression) in the nursing infant, breastfeeding is contraindicated during therapy and for at least 48 hours after the last dose.
Teratogenic Risk	Cytarabine is embryotoxic and teratogenic in animals. In humans, first-trimester exposure is associated with an increased risk of congenital malformations, including skeletal and central nervous system anomalies. Second and third trimester use may cause fetal growth restriction, myelosuppression, and neonatal pancytopenia. Risk is dose-dependent and increased with combination chemotherapy.