Cytosine Arabinoside

From Anvita Health Wiki

Contents 1 Introduction 2 Indications 3 Dosage 4 Pharmacokinetics 5 Monitor 6 Adverse-effects 7 Drug-interactions 8 Test-interactions 9 Mechanism-of-action 10 More General Terms 11 Additional Terms 12 Internet Database 13 References

Introduction

• Tradenames: Cytosar, Depocyt.

Indications

• leukemia

• acute myeloid leukemia ( AML)
• acute lymphocytic leukemia ( ALL)
• chronic myeloid leukemia ( CML)
• meningial leukemia
• acute non-lymphocytic leukemia

• Hodgkin's & non-Hodgkin's lymphoma

Dosage

• 60-200 mg/m2 as continuous IV infusion over 5-10 days
• 10-30 mg/m2 intrathecally 2-3 times weekly

• use normal saline or Elliot's B solution for diluent

• 100 mg/m2 IV or SC every 12 hours for 5 days every month
• doses up to 3 g/m2 IV every 12 hours have been given

• Powder for injection: 100 mg, 200 mg, 1g, 2g.
• Injection: Liposomal ( Depocyt).
• Caution:

• incompatible with 5-fluorouracil, gentamicin, insulin, methylprednisolone, nafcillin, oxacillin, penicillin G

Pharmacokinetics

• widely distributed to tissues
• deactivated by the liver
• 72% recovered in the urine
• 1/2life is 2-3 hours ( plasma); 2-10 hours ( CNS)
  

• elimination via liver
• elimination via kidney
• 1/2life = 2-10 hours

Monitor

• complete blood count ( CBC)
• liver function tests ( LFTs)

Adverse-effects

• common (> 10%)

• oral ulceration, anal ulceration, hepatic dysfunction, fever, rash, thrombophlebitis, bleeding, nausea/vomiting, diarrhea, mucositis

• less common (1-10%)

• dizziness, headache, skin freckles, itching, alopecia, sepsis, pneumonia, cellulitis at injection site, urinary retention, neuritis, cardiomegaly, somnolence, peripheral neuropathy, malaise, confusion, myalgia, bone pain, sudden respiratory depression leading to pulmonary edema

• other [2]

• myelosuppression
• conjunctivitis (most patients need prophylactic glucocorticoid eyedrops)
• cerebellar toxicity
• neurotoxicity
• flu-like syndrome

Drug-interactions

• cytarabine decreases digoxin bioavailability
• gentamicin
• flucytosine

Test-interactions

• increases serum K+
• decreases serum protein

Mechanism-of-action

• antimetabolite
• affects rapidly dividing cells in G1 to S phase Mechanism of drug resistance:
• defective transport via the nucleoside transporter
• diminished activity of deoxycytidine kinase
• increased drug inactivation via by activation of cytidine deaminase

More General Terms

• antineoplastic agent (chemotherapeutic agent)
• antimetabolite

Additional Terms

• cytidine deaminase; cytidine aminohydrolase (CDA, CDD)
• deoxycytidine kinase (DCK)
• Na+/nucleoside cotransporter or nucleoside transporter

Internet Database

PubChem: 6253
PubChem: 596

References

1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 596
2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
4. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 533

cytosine arabinoside; cytarabine (Cytosar, ARA-C, HiDAC, Depocyt)