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Class: Pyrimidine analog
- Sterile powder for reconstitution 100 mg, 500 mg, 1 g, 2 g vials
Cytarabine exhibits cell-phase specificity, primarily killing cells undergoing DNA synthesis (S-phase) and under certain conditions, blocking the progression of cells from the G 1 -phase to the S-phase.
Distribution t ½ is about 10 min.
Metabolized by deoxycytidine kinase and other nucleotide kinases to nucleotide triphosphate (active). Inactivated by a pyrimidine nucleotide deaminase to nontoxic uracil derivative.
Elimination t ½ is about 1 to 3 h. About 80% is excreted in the urine within 24 h (90% of which is excreted as ara-U).
Indications and Usage
Acute lymphocytic leukemia, acute and chronic myelocytic leukemia, meningeal leukemia, erythroleukemia, non-Hodgkin lymphoma.
Hodgkin disease, bone marrow transplantation.
Dosage and AdministrationAcute Leukemia Induction
Continuous IV infusion or rapid injection 100 to 200 mg/m 2 /day or 3 mg/kg/day as a continuous IV infusion over 24 h or in divided doses by rapid injection for 5 to 10 days with the courses repeated about every 2 wk.Children
Continuous IV infusion or rapid injection 100 to 200 mg/m 2 /day as a continuous IV infusion over 24 h or in divided doses by rapid injection for 5 to 10 days with the courses repeated about every 2 wk.Acute Leukemia Maintenance
Subcutaneous 1 mg/kg/dose 1 or 2 times/wk.Children
Subcutaneous or IM 1 to 1.5 mg/kg/dose every 1 to 4 wk.Alternate maintenance regimen
70 to 200 mg/m 2 /day IV for 2 to 5 days repeated every mo.Acute Nonlymphocytic Leukemia (Combination with Other Chemotherapeutic Drugs)
Continuous infusion 100 mg/m 2 /day on days 1 through 7, or 100 mg/m 2 every 12 h for 7 days.Alternate regimen
Cytarabine 10 mg/m 2 /dose subcutaneously twice daily for 7 to 14 days in combination with other chemotherapeutic drugs.Children
Continuous infusion 100 mg/m 2 /day on days 1 through 7, or 100 mg/m 2 every 12 h for 7 days.Refractory Acute Leukemia or Lymphomas
Adults High-dose cytarabine
IV 2,000 to 3,000 mg/m 2 every 12 h for 2 to 6 days. Suspend or modify the dose of cytarabine if ANC is less than 1,000/mm 3 or the platelet count is less than 50,000/mm 3 .Children High-dose cytarabine
IV 1,000 to 3,000 mg/m 2 every 12 h for 2 to 6 days. Suspend or modify the dose of cytarabine if ANC is less than 1,000/mm 3 or the platelet count is less than 50,000/mm 3 .Adjustment in Hepatic Function Impairment
May require dosage reduction; specific guidelines not established.Children
Follow dosage adjustment guidelines recommended for adults.Meningeal Leukemia
Intrathecally to 75 mg/m 2 at intervals ranging from once a day for 4 days to once every 4 days (range, 2 to 7 days).Children
Intrathecally to 75 mg/m 2 at intervals ranging from once a day for 4 days to once every 4 days (range, 2 to 7 days). Many clinicians recommend dosing intrathecal cytarabine by the child's age.Pretreatment Regimen
Prophylactic use of corticosteroid eye drops decreases the risk of conjunctivitis or keratitis. Begin prophylactic therapy prior to chemotherapy and continue for 48 h after the last dose of cytarabine.
- Administer by subcutaneous/IM injection, by IV injection or infusion, or intrathecally.
- Rotate injection sites for subcutaneous/IM administration.
- High dose
- Dilute with preservative-free sodium chloride 0.9%.
- Give IV infusion over 1 to 3 h.
- Dilute with an isotonic buffered diluent without preservative such as Lactated Ringer's injection or sodium chloride 0.9%.
- IV infusion
- Reconstitute with bacteriostatic water for injection (with 0.9% benzyl alcohol). May be further diluted with greater than 50 mL of sodium chloride 0.9% for IV infusion.
- Give by bolus injection over 1 to 3 min through a running IV line; infuse IV over 15 min in greater than 50 mL of sodium chloride 0.9%; continuous IV infusion over 5 days. Cytarabine doses are often infused over 30 min.
- Smaller volumes of diluent can be used to prepare a 100 mg/mL solution for subcutaneous/IM injection.
- Store at room temperature.
- When reconstituted with bacteriostatic water for injection (with benzyl alcohol), cytarabine is stable for 2 days at room temperature. Use preservative-free cytarabine solutions within 24 h of reconstitution. Discard if solution appears hazy.
- Diluted cytarabine solutions (concentration 0.5 mg/mL) are stable for 8 days at room temperature when diluted with sterile water, sodium chloride 0.9%, or dextrose 5%.
Prior therapy with L-asparaginase may increase the risk of acute pancreatitis.Digoxin
Oral absorption of digoxin may be decreased.Gentamicin
Gentamicin effectiveness against Klebsiella pneumoniae strains may be decreased.Quinolone antibiotics
Cytarabine may decrease the oral absorption of quinolone antibiotics.
Laboratory Test Interactions
None well documented.
Headache, dizziness; seizures, cerebral or cerebellar dysfunction presenting as personality changes, somnolence, coma, ataxia, dysarthria, and nystagmus (high dose); sensory neuropathy (high dose); necrotizing leukoencephalopathy with intrathecal cytarabine and cranial radiation.
Rash; cellulitis; thrombophlebitis; palmar-plantar erythrodysesthesia; severe rash with desquamation (high dose).
Nausea; vomiting; anorexia; mucositis; diarrhea; transient elevation of LFTs; neutropenic colitis; severe GI ulceration (high dose).
Bone marrow suppression.
Pulmonary edema, diffuse interstitial pneumonitis (high dose).
Cytarabine syndrome; arthralgias; myalgias; chest pain; fever; general feeling of discomfort or weakness; reddened eyes; skin rash.
Hemorrhagic conjunctivitis, corneal toxicity, photophobia (high dose).
For induction therapy, treat patients in a facility with laboratory and supportive resources sufficient to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity. Less serious toxicity includes nausea, vomiting, diarrhea, abdominal pain, oral ulceration, and hepatic function impairment. The physician must judge possible benefit to the patient against known toxic effects of the drug in considering the advisability of therapy.
Anemia, leukopenia, thrombocytopenia, megaloblastosis, and reduced reticulocytes can be expected. The severity of these reactions is dose- and schedule-dependent.
MonitorBone marrow examinations
During induction therapy, perform leukocyte and platelet counts daily. Perform bone marrow examinations frequently after blasts have disappeared from the peripheral blood.Drug-induced marrow depression
Suspend or modify therapy when drug-induced marrow depression results in a platelet count less than 50,000/mm 3 or a polymorphonuclear granulocyte count less than 1,000/mm 3.
Category D .
Conventional cytarabine is indicated for use in children.
Cases of anaphylaxis have occurred resulting in acute cardiopulmonary arrest which required resuscitation. This occurred immediately after IV administration.
Patients with renal function impairment may have a higher likelihood of CNS toxicity after high-dose cytarabine. Use the drug with caution and possibly at reduced doses in patients with poor kidney function.
Patients with hepatic function impairment may have a higher likelihood of CNS toxicity after high-dose cytarabine. Use the drug with caution and possibly at reduced doses in patients with poor liver function.
Benzyl alcohol is contained in the diluent for some conventional cytarabine products. Benzyl alcohol has been reported to be associated with a fatal “gasping syndrome” in premature infants. Do not use conventional cytarabine injection with benzyl alcohol intrathecally.
May cause local irritation or phlebitis. Refer to your institution specific protocol.
Viral, bacterial, fungal, parasitic, or saprophytic infections in any location in the body may be associated with the use of cytarabine alone or in combination with other immunosuppressive agents.
Hyperuricemia may occur because of rapid cell lysis; monitor serum uric acid. Minimize effects of hyperuricemia with hydration, urinary alkalinization, and allopurinol.
If used intrathecally, do not use a diluent with benzyl alcohol.
Peripheral motor and sensory neuropathies have occurred.
Enhanced neurotoxicity has been associated with concurrent use of intrathecal cytarabine and other cytotoxic agents administered intrathecally.
- Inform patients about the expected adverse reactions of headache, nausea, vomiting, and fever, and about the early signs and symptoms of neurotoxicity. Instruct patients to seek medical attention if signs or symptoms of neurotoxicity develop, or if oral dexamethasone is not well tolerated.
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