CYTARABINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CYTARABINE (CYTARABINE).
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.
| 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. |
| Molecular Weight | 243.22 |
| Action Class | Antimetabolites |
| Brand Substitutes | Cytaneon 1000mg Injection, Cytarine 1000mg Injection, Oncotar 1000mg Injection, Cytraz 1000mg Injection, Cytraze 1000mg Injection |
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. |
| 1st trimester | Contraindicated due to teratogenicity; major congenital malformations reported in first trimester exposure. |
| 2nd trimester | Use only if clearly needed; risk of fetal harm, including growth restriction and CNS abnormalities. |
| 3rd trimester | Use only if clearly needed; risk of neonatal myelosuppression and other adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for CYTARABINE (CYTARABINE).
| Placental transfer | Cytarabine crosses the placenta; fetal concentrations may reach maternal levels. Active metabolite ara-CTP accumulates in fetal liver. |
| Breastfeeding | Cytarabine is excreted into breast milk in low amounts; potential for serious adverse reactions in nursing infants (e.g., immunosuppression, growth retardation). Manufacturers recommend discontinuing breastfeeding during therapy and for at least 1 week after last dose. |
■ 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.
| Serious Effects |
Hypersensitivity to cytarabine or any componentSevere bone marrow suppression (unless part of planned treatment)Pregnancy (first trimester, unless lifesaving)
| 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. |
| Food/Dietary | No significant food interactions; maintain adequate hydration. |
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| Lactation Rating | L5 - Hazardous (Avoid) |
| 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. |
| Fetal Monitoring | Monitor complete blood count (CBC) with differential, liver function tests (LFTs), renal function, and serum uric acid levels before and during therapy. Perform fetal ultrasound for growth and anatomy with known or suspected intrauterine exposure. Monitor for signs of fetal distress (e.g., non-stress test, biophysical profile) in later pregnancy. Assess neonatal CBC at birth if maternal use near term. |
| Fertility Effects | Cytarabine may cause ovarian suppression and premature ovarian failure in females; reversible or irreversible azoospermia in males. Gonadotoxicity is dose-related. Pre-treatment fertility preservation counseling is recommended. |
| Clinical Pearls | Monitor for cerebellar toxicity, especially in high-dose regimens; dose adjustment required in renal impairment (CrCl <60 mL/min); use corticosteroid eye drops to prevent conjunctivitis with high-dose therapy; administer IV over 1-3 hours for high-dose; intrathecal formulation contains no preservatives; coadministration with methotrexate increases toxicity. |
| Patient Advice | You may experience nausea, vomiting, and diarrhea; take antiemetics as prescribed. · Report any vision changes, difficulty walking, or confusion immediately. · Use effective contraception during treatment and for 6 months after. · Avoid live vaccines during and for 3 months after therapy. · Drink plenty of fluids to prevent kidney problems. · Notify your doctor if you develop fever, sore throat, or unusual bruising/bleeding. |