Introduction
A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)
Uses
Cytarabine is a pyrimidine nucleoside analogue used to treat acute non-lymphocytic leukemia, lymphocytic leukemia, and the blast phase of chronic myelocytic leukemia.
For the treatment of acute non-lymphocytic leukemia, acute lymphocytic leukemia and blast phase of chronic myelocytic leukemia.
Cytarabine is indicated in combination with daunorubicin for the treatment of newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients 1 year and older.
Associated Conditions
Pharmacodynamics
Cytarabine is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute myelogenous leukemia and meningeal leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Cytarabine is metabolized intracellularly into its active triphosphate form (cytosine arabinoside triphosphate). This metabolite then damages DNA by multiple mechanisms, including the inhibition of alpha-DNA polymerase, inhibition of DNA repair through an effect on beta-DNA polymerase, and incorporation into DNA. The latter mechanism is probably the most important. Cytotoxicity is highly specific for the S phase of the cell cycle.
Mechanism of Action
Cytarabine acts through direct DNA damage and incorporation into DNA. Cytarabine is cytotoxic to a wide variety of proliferating mammalian cells in culture. It exhibits cell phase specificity, primarily killing cells undergoing DNA synthesis (S-phase) and under certain conditions blocking the progression of cells from the G1 phase to the S-phase. Although the mechanism of action is not completely understood, it appears that cytarabine acts through the inhibition of DNA polymerase. A limited, but significant, incorporation of cytarabine into both DNA and RNA has also been reported.
Absorption
Less than 20% of the orally administered dose is absorbed from the gastrointestinal tract.
Protein Binding
13%
Route of Elimination
The primary route of elimination of cytarabine is metabolism to the inactive compound ara-U, followed by urinary excretion of ara-U.
Half Life
10 minutes
Toxicity
Cytarabine syndrome may develop - it is characterized by fever, myalgia, bone pain, occasionally chest pain, maculopapular rash, conjunctivitis, and malaise.
Food Interactions
No interactions found.
Dosage
Intrathecal Use in Meningeal Leukemia: Cytarabine injection has been used intrathecally in acute leukemia in doses ranging from 5 mg/m2 to 75 mg/m2 of body surface area.
Use in Children: Appropriate studies with cytarabine have not been performed in the paediatric population. However, paediatric specific problems that would limit the usefulness of this medication in children are not expected.
Use in the Elderly: Although studies with cytarabine have not been performed in the geriatric population, geriatric specific problems that would limit the usefulness of this medication in the elderly are not expected. Elderly patients are, however, more likely to have age related renal function impairment, which may require reduction of dosage in patients receiving cytarabine.
