Drug information of Cytarabine

Mechanism of effect

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

Pharmacodynamic

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

Pharmacokinetics

Cytarabine is rapidly metabolized and is not effective orally; less than 20 percent of the orally administered dose is absorbed from the gastrointestinal tract. Protein binding:13%.Metabolism: Hepatic.. 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

Drug indications

non-Hodgkins lymphoma , chronic lymphocytic leukemia , acute lymphocytic leukemia , the blast phase of chronic myelocytic leukemia. , Acute Nonlymphocytic Leukemia

Dosage

Usual Adult Dose for Acute Nonlymphocytic Leukemia As a part of a combination chemotherapy: 100 mg/m2/day by continuous IV infusion (days 1 to 7) or 100 mg/m2 IV every 12 hours (days 1 to 7) with an anthracycline. Usual Adult Dose for non-Hodgkin's Lymphoma Acute Leukemia Induction: 100 to 200 mg/m2/day or 2 to 6 mg/kg/day as a continuous IV infusion over 24 hours or in divided doses by rapid injection for 5 to 10 days. This course may be repeated approximately every 2 weeks.

Drug contraindications

hypersensitivity to drug or its components.

Side effects

nausea , chest pain , abdominal pain , vomiting , Hepatic dysfunction , rash , pruritus , severe mucocutaneous reactions , thrombocytopenia , leukopenia , fever , myalgia , Bone pain , Alopecia , Infections , anorexia , malaise , conjunctivitis , hemorrhage , urinary retention , pneumonia

Interactions

Trastuzumab , Allopurinol , Vitamin A , Vitamin E , Flucytosine , Treosulfan , Adenovirus types 4 and 7 live, oral , Remdesivir , Meningococcal conjugate vaccine

Alerts

Only physicians experienced in cancer chemotherapy should use Cytarabine Injection. For induction therapy patients should be treated in a facility with laboratory and supportive resources sufficient to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity. The main toxic effect of Cytarabine Injection is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Less serious toxicity includes nausea, vomiting, diarrhea and abdominal pain, oral ulceration, and hepatic dysfunction.

Points of recommendation

1-Patients receiving Cytarabine Injection must be monitored closely. Frequent platelet and leukocyte counts and bone marrow examinations are mandatory. 2-When large intravenous doses are given quickly, patients are frequently nauseated and may vomit for several hours post injection. This problem tends to be less severe when the drug is infused. 3-The human liver apparently detoxifies a substantial fraction of an administered dose. In particular, patients with renal or hepatic function impairment may have a higher likelihood of CNS toxicity after high-dose Cytarabine treatment. Use the drug with caution and possibly at reduced dose in patients whose liver or kidney function is poor. 4-Periodic checks of bone marrow, liver and kidney functions should be performed in patients receiving Cytarabine Injection. 5-Like other cytotoxic drugs, Cytarabine Injection may induce hyperuricemia secondary to rapid lysis of neoplastic cells. The clinician should monitor the patient's blood uric acid level and be prepared to use such supportive and pharmacologic measures as might be necessary to control this problem. 6-Acute pancreatitis has been reported to occur in a patient receiving Cytarabine by continuous infusion and in patients being treated with Cytarabine who have had prior treatment with L-asparaginase.

Pregnancy level

D

Related drugs

Asparaginase , Thioguanine , Fludarabine phosphate , Hydroxy urea , Clofarabine , Pemetrexed , Pralatrexate , Nelarabine