Cytosine Arabinoside

Uses

Cytosine Arabinoside is used for Leukaemic meningitis, Induction and maintenance of remission in acute leukaemias

Cytosine Arabinoside is also used to associated treatment for these conditions: Acute Lymphocytic Leukemia (ALL), Acute Myeloid Leukemia (AML), Acute Promyelocytic Leukemia (APL), Leptomeningeal Metastases, Meningeal leukemia, Non-Hodgkin's Lymphoma (NHL), Blast phase Chronic myelocytic leukemia

How Cytosine Arabinoside works

Cytosine Arabinoside acts through direct DNA damage and incorporation into DNA. Cytosine Arabinoside 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.

Dosage

Cytosine Arabinoside dosage

Intrathecal (Adult)-

• Leukaemic meningitis:5-75 mg/m2 or 30-100 mg once every 2-7 days to once daily for 4 or 5 days.
• For lymphomatous meningitis: 50 mg every 2 wk for 5 doses, then every 4 wk for 5 doses.

Parenteral (Adult)-Induction and maintenance of remission in acute leukaemias:

• As monotherapy: 200 mg/m2 daily by continuous IV infusion for 5 days, at intervals of approx 2 wk.
• In combination therapy: 100 mg/m2 bid by rapid IV inj or 100 mg/m2 daily by continuous IV infusion both for 7 days. Maintenance: 1-1.5 mg/kg once or twice wkly via IV or SC.

Intravenous: Reconstitute with bacteriostatic water for inj (standard-dose), further dilute in 250-1,000 ml NaCl 0.9% or dextrose 5% in water for infusion.

Intrathecal: Reconstitute with preservative free NaCl 0.9%, further dilute with Elliot’s B soln, NaCl 0.9% or lactated Ringer’s inj to preferred final vol (up to 12 ml).

Side Effects

Nausea, vomiting, fever, rash, diarrhoea, anorexia, oral and anal inflammation or ulceration, hepatic dysfunction, headache, weakness, confusion, thrombocytopenia, fatigue.

Toxicity

Cytosine Arabinoside syndrome may develop - it is characterized by fever, myalgia, bone pain, occasionally chest pain, maculopapular rash, conjunctivitis, and malaise.

Precaution

Patient with previous drug-induced bone marrow suppression. Renal or hepatic impairment. Pregnancy and lactation.

Interaction

May reduce efficacy of 5-fluorocytosine, digoxin, gentamicin. May increase risk of neurotoxicity with other cytotoxic agents (intrathecal).

Food Interaction

Cytosine Arabinoside Drug Interaction

Unknown: lorazepam, lorazepam, sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprim, ubiquinone, ubiquinone, copper gluconate, copper gluconate, glycerin, glycerin, acetaminophen, acetaminophen, bioflavonoids, bioflavonoids, sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprim, ondansetron, ondansetron

Cytosine Arabinoside Disease Interaction

Major: infections, myelosuppressionModerate: hepatic dysfunction, renal dysfunction

Elimination Route

Less than 20% of the orally administered dose is absorbed from the gastrointestinal tract.

Half Life

10 minutes

Elimination Route

The primary route of elimination of cytarabine is metabolism to the inactive compound ara-U, followed by urinary excretion of ara-U.

Pregnancy & Breastfeeding use

Pregnancy Category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Contraindication

Patient with active meningeal infection.

Acute Overdose

Symptoms: Irreversible CNS toxicity and death. Severe arachnoiditis including encephalopathy.

Management: Therapy cessation followed by treatment of ensuing bone marrow depression including whole blood or platelet transfusion and antibiotics. Maintain vital functions.

Storage Condition

IV/SC: Store between 15-25°C. Intrathecal: Store between 2-8°C. Avoid freezing.

Innovators Monograph

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