CYTOSAR-U
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CYTOSAR-U (CYTOSAR-U).
Cytarabine is an antimetabolite that inhibits DNA synthesis by competing with cytidine for incorporation into DNA, causing chain termination and inhibiting DNA polymerase.
| Metabolism | Primarily metabolized by deoxycytidine kinase to ara-CMP, further phosphorylated to active ara-CTP. Inactivated by cytidine deaminase to uracil arabinoside (ara-U). Hepatic and extrahepatic metabolism. |
| Excretion | Cytosar-U (cytarabine) is primarily excreted renally as inactive metabolite uracil arabinoside (Ara-U). Approximately 70-80% of a dose is recovered in urine within 24-48 hours, with <10% excreted as unchanged drug. Biliary/fecal elimination is minimal (<5%). |
| Half-life | The terminal elimination half-life of cytarabine is 1-3 hours for the initial phase (alpha) and 2-6 hours for the terminal phase (beta), with a mean of approximately 2.5 hours. In patients with renal impairment, half-life may be prolonged up to 6-8 hours, requiring dose adjustment. |
| Protein binding | Cytarabine is minimally protein bound (13%) primarily to albumin. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 3 L/kg (range 1.5-4.5 L/kg), indicating extensive tissue distribution, including penetration into CSF (approximately 20-40% of plasma levels). |
| Bioavailability | Subcutaneous: Bioavailability is 80-90% with peak levels at 30-60 minutes. Oral: Bioavailability is <20% due to extensive first-pass metabolism, thus not used. Intrathecal: Direct administration yields 100% bioavailability in CSF. |
| Onset of Action | Intravenous: Onset of cytotoxic effect occurs within minutes as cytarabine is rapidly converted to active triphosphate. Intrathecal: Onset of antileukemic effect occurs within 1-2 hours. Subcutaneous: Onset is within 30-60 minutes. |
| Duration of Action | Duration of cytotoxic effect is 8-12 hours post IV administration, correlating with intracellular ara-CTP retention. Intrathecal: Duration of CSF drug levels is 6-24 hours. For high-dose regimens, duration of myelosuppression is 7-10 days. |
| Molecular Weight | 243.22 |
Cytarabine 100-200 mg/m² IV continuous infusion over 24 hours for 5-7 days (induction) or 1-3 g/m² IV every 12 hours for 6 doses (high-dose cytarabine).
| Dosage form | INJECTABLE |
| Renal impairment | For CrCl 30-60 mL/min: reduce dose to 60% of normal. For CrCl <30 mL/min: reduce dose to 40% of normal. Monitor for neurotoxicity. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 25%. Child-Pugh C: reduce dose by 50% or consider alternative. |
| Pediatric use | Induction: 100 mg/m²/day IV continuous infusion for 5-7 days. High-dose: 1-3 g/m² IV every 12 hours for 6 doses (adjusted per protocol). |
| Geriatric use | Start at reduced dose (e.g., 50-75% of standard) due to increased risk of myelosuppression and neurotoxicity. Monitor renal function. |
| 1st trimester | Contraindicated due to teratogenicity; associated with fetal malformations, chromosomal aberrations, and spontaneous abortion. |
| 2nd trimester | Contraindicated; risk of fetal harm outweighs potential benefit. |
| 3rd trimester | Contraindicated; may cause neonatal bone marrow suppression and other toxicities. |
Clinical note
Comprehensive clinical and safety monograph for CYTOSAR-U (CYTOSAR-U).
| Placental transfer | Cytarabine crosses the placenta readily. Fetal concentrations may be similar to maternal levels; teratogenic effects observed in animal studies and human cases. |
| Breastfeeding | Cytarabine is present in breast milk. Potential for serious adverse reactions in nursing infants includes immunosuppression and bone marrow toxicity. Discontinue breastfeeding or discontinue drug, taking into account importance of drug to mother. |
■ FDA Black Box Warning
Cytarabine can cause severe bone marrow suppression, including granulocytopenia, thrombocytopenia, and anemia. High doses may cause severe CNS toxicity, including cerebellar toxicity, cerebral edema, and coma. Intrathecal administration can cause arachnoiditis and myelopathy. Do not use with other intrathecal agents containing preservatives.
| Serious Effects |
Hypersensitivity to cytarabine or any component of the formulationPregnancy
| Precautions | Severe myelosuppression with infection risk; monitor blood counts frequently. High-dose therapy increases risk of CNS toxicity (cerebellar, cerebral, ocular). Tumor lysis syndrome may occur. Hepatotoxicity and pancreatitis reported. Intravenous administration requires supervision of physician experienced in cancer chemotherapy. Intrathecal use must avoid preservatives. |
| Food/Dietary | Grapefruit and grapefruit juice may inhibit CYP3A4 metabolism of cytarabine, potentially increasing toxicity; avoid concomitant use. No other significant food interactions reported. Maintain adequate hydration to prevent hyperuricemia. |
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| Lactation Rating | L5 (Contraindicated) or 'Avoid' |
| Teratogenic Risk | Cytarabine is teratogenic. First trimester: high risk of congenital malformations (craniofacial, skeletal, neural tube defects). Second and third trimesters: risk of fetal growth restriction, preterm birth, and myelosuppression. Avoid in pregnancy unless benefit outweighs risk. |
| Fetal Monitoring | Monitor complete blood count (CBC) with differential, liver function tests, renal function, and uric acid. Fetal ultrasound for growth and anomalies. Nonstress test or biophysical profile in third trimester. Monitor for signs of infection, bleeding, and tumor lysis syndrome. |
| Fertility Effects | Cytarabine can impair fertility in both males and females. In males, may cause oligospermia, azoospermia, and testicular atrophy. In females, may cause amenorrhea, ovarian failure, and premature menopause. Effects may be irreversible. |
| Clinical Pearls | Cytosar-U (cytarabine) is a pyrimidine analog antimetabolite used primarily in acute myeloid leukemia (AML) and non-Hodgkin lymphoma. High-dose regimens (>1 g/m²) can cause cerebellar toxicity, especially in patients over 60; monitor for dysmetria and ataxia. Concomitant use with fludarabine increases risk of severe myelosuppression. Administer with adequate hydration and allopurinol to prevent tumor lysis syndrome. For intrathecal use, preservative-free formulation is mandatory. |
| Patient Advice | This medication can lower your white blood cell count, increasing infection risk; report fever or chills immediately. · Nausea and vomiting are common; take antiemetics as prescribed. · You may experience temporary hair loss, skin rash, or mouth sores; use a soft toothbrush and avoid spicy foods. · Avoid grapefruit and grapefruit juice during treatment. · Do not receive live vaccines (e.g., MMR, shingles) during or shortly after treatment. · Use effective contraception during therapy and for at least 6 months after completion. |