Cancyt

Indications

• Acute myeloid leukemia
• Acute lymphoblastic leukemia
• Meningeal leukemia
• Lymphomatous meningitis
• Relapsed or refractory acute lymphoblastic leukemia

Dosage

Adults: Consult local protocol for induction doses in acute myeloid leukemia or lymphomatous meningitis. Commonly, it is given by intravenous infusion or injection, with adjustments as necessary for renal impairment. Specific dosing should be guided by clinical protocol.

Mechanism of action

Cytarabine acts through direct DNA damage and incorporation into DNA. It is converted intracellularly to cytarabine triphosphate (ara-CTP), which inhibits DNA polymerase by competing with deoxycytidine triphosphate, thereby blocking DNA synthesis. Cytarabine also exhibits cell phase specificity, primarily targeting cells in the S-phase of the cell cycle. Its actions include inhibition of DNA repair processes and incorporation into both DNA and RNA, contributing to its cytotoxic effects.

Pharmacodynamics

Cytarabine is classified as an antineoplastic anti-metabolite. It masquerades as a pyrimidine, which are essential building blocks of DNA, preventing their incorporation during the S-phase of the cell cycle. This results in halted cell division and subsequent cell death, particularly in rapidly dividing cancer cells. The drug also has immunosuppressive properties but does not affect established antibody titers or delayed hypersensitivity reactions.

Pharmacokinetics

Cytarabine is metabolized intracellularly to its active triphosphate form. Following administration, the drug exhibits rapid distribution and is primarily eliminated through metabolism in the liver and excretion via the kidneys. Dose adjustments may be necessary in patients with renal or hepatic impairment. The half-life of cytarabine varies, but it generally ranges from 1 to 3 hours in plasma.

Adverse effects

• Alopecia
• Anxiety
• Appetite decrease
• Arthralgia
• Capillary leak syndrome
• Chills
• Diarrhoea
• Dizziness
• Drowsiness
• Fatigue
• Fever
• Gastrointestinal discomfort
• Headache
• Hepatic disorders
• Hyperbilirubinaemia
• Hyperhidrosis
• Hypersensitivity
• Increased infection risk
• Nausea
• Paralysis
• Vomiting
• Vision disorders

Interactions

• Cytarabine + flucytosine: Severe interaction (decreases concentration)
• Cytarabine + live vaccines: Unknown interaction (increases risk of generalized infection, possibly life-threatening)

Precautions

• Caution in patients with hepatic impairment (use with caution in mild-to-moderate impairment; avoid in severe impairment)
• Caution in patients with renal impairment (use with caution in mild-to-moderate impairment; avoid in severe impairment)
• Patients with cardiac disease should be monitored
• Patients should be counselled on the effects on driving and performance of skilled tasks due to increased risk of dizziness and drowsiness

Pregnancy

Manufacturer advises to avoid use during pregnancy due to teratogenic effects observed in animal studies.

Breast-feeding

Discontinue breastfeeding during treatment with cytarabine.

Storage

Store in a refrigerator at 2–8°C.

Formulations

• Solution for injection
• Solution for infusion

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. Cytarabine is converted intracellularly to the nucleotide, cytarabine triphosphate (ara-CTP, cytosine arabinoside triphosphate). Although the exact mechanism(s) of action of cytarabine has not been fully elucidated, cytarabine triphosphate appears to inhibit DNA polymerase by competing with the physiologic substrate, deoxycytidine triphosphate, resulting in the inhibition of DNA synthesis. Although limited, incorporation of cytarabine triphosphate into DNA and RNA may also contribute to the cytotoxic effects of the drug. Cytarabine is a potent immunosuppressant which can suppress humoral and/or cellular immune responses; however, the drug does not decrease preexisting antibody titers and has no effect on established delayed hypersensitivity reactions. Cytarabine liposome injection is a sustained-release formulation of the active ingredient cytarabine designed for direct administration into the cerebrospinal fluid (CSF). Cytarabine is a cell cycle phase-specific antineoplastic agent, affecting cells only during the S-phase of cell division. Intracellularly, cytarabine is converted into cytarabine-5'-triphosphate (ara-CTP), which is the active metabolite. The mechanism of action is not completely understood, but it appears that ara-CTP acts primarily through inhibition of DNA polymerase. Incorporation into DNA and RNA may also contribute to cytarabine cytotoxicity. Cytarabine is cytotoxic to a wide variety of proliferating mammalian cells in culture. /Cytarabine liposome injection/

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.