Cytarabine


Generic Medicine Info
Indications and Dosage
Intrathecal
Leukaemic meningitis
Adult: 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
Induction and maintenance of remission in acute leukaemias
Adult: 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.
Reconstitution
IV: Reconstitute w/ 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 w/ preservative free NaCl 0.9%, further dilute w/ Elliot’s B soln, NaCl 0.9% or lactated Ringer’s inj to preferred final vol (up to 12 mL).
Incompatibility
Y-site: Incompatible w/ caspofungin, allopurinol, ganciclovir, gallium nitrate.
Contraindications
Patient w/ active meningeal infection.
Special Precautions
Patient w/ previous drug-induced bone marrow suppression. Renal or hepatic impairment. Pregnancy and lactation.
Adverse Reactions
Nausea, vomiting, fever, rash, diarrhoea, anorexia, oral and anal inflammation or ulceration, hepatic dysfunction, headache, weakness, confusion, thrombocytopenia, fatigue.
Potentially Fatal: Chemical arachnoiditis, bone marrow suppression. Viral, fungal, bacterial, saprophytic or parasitic infections. Pulmonary toxicity, sudden resp distress syndrome and pulmonary oedema (high-doses).
IT/IV/Parenteral/SC: D
Monitoring Parameters
Monitor LFTs, CBC w/ differential and platelet count, BUN, serum uric acid, serum creatinine. Monitor for signs of an immediate reaction, chemical arachnoiditis, neurotoxicity.
Overdosage
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.
Drug Interactions
May reduce efficacy of 5-fluorocytosine, digoxin, gentamicin. May increase risk of neurotoxicity w/ other cytotoxic agents (intrathecal).
Action
Description:
Mechanism of Action: Cytarabine inhibits deoxyribonucleic acid (DNA) synthesis specifically at the S-phase of the cell cycle. It also has an antiviral and immunosuppressant activity.
Pharmacokinetics:
Absorption: Time to peak plasma concentration: 20-60 min (IM/SC).
Distribution: Crosses the placenta and blood-brain barrier w/ CSF levels of 40-50% of plasma level. Volume of distribution: 3±11.9 L/kg. Plasma protein binding: 13%.
Metabolism: Converted by phosphorylation to an active form followed by deamination in the liver and kidneys to inactive uracil arabinoside (ARA-U).
Excretion: Via urine (mostly as inactive metabolite; approx 10% as unchanged drug). Elimination half-life: Initial: Approx 10 min (IV); terminal: 1-3 hr (IV), 100-263 hr (intrathecal).
Chemical Structure

Chemical Structure Image
Cytarabine

Source: National Center for Biotechnology Information. PubChem Database. Cytarabine, CID=6253, https://pubchem.ncbi.nlm.nih.gov/compound/Cytarabine (accessed on Jan. 22, 2020)

Storage
IV/SC: Store between 15-25°C. Intrathecal: Store between 2-8°C. Avoid freezing.
MIMS Class
Cytotoxic Chemotherapy
ATC Classification
L01BC01 - cytarabine ; Belongs to the class of antimetabolites, pyrimidine analogues. Used in the treatment of cancer.
References
Anon. Cytarabine (Conventional). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 13/01/2016.

Anon. Cytarabine (Liposomal). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 13/01/2016.

Buckingham R (ed). Cytarabine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 13/01/2016.

Cytarabine for Injection, 1 g/vial [Bedford Labs]: Recall: Risk of Lack of Sterility. U.S. FDA. https://www.fda.gov/. Accessed 13/01/2016.

Cytarabine Injection (Mylan Institutional LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 13/01/2016.

Joint Formulary Committee. Cytarabine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 13/01/2016.

McEvoy GK, Snow EK, Miller J et al (eds). Cytarabine. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 13/01/2016.

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