CYTARABINE

CYTARABINE
(sye-tare'a-been)
Cytosar-U, DepoCyt
Classifications: antineoplastic; antimetabolite, purine antagonist;
Therapeutic: antineoplastic; antimetabolite
Prototype: 6-Mercaptopurine
Pregnancy Category: D

Availability

10 mg/mL liposomal, 20 mg/mL, 100 mg, 500 mg, 1 g, 2 g injection

Action

Pyrimidine analog with cell phase specificity affecting rapidly dividing cells in S phase (DNA synthesis). In certain conditions prevents development of cell from G₁ to S phase. Interferes with DNA and RNA synthesis in rapidly growing cells.

Therapeutic Effect

Antineoplastic agent which has strong myelosuppressant activity. Immunosuppressant properties are exhibited by obliterated cell-mediated immune responses, such as delayed hypersensitivity skin reactions.

Uses

To induce and maintain remission in acute myelocytic leukemia, acute lymphocytic leukemia, and meningeal leukemia and for treatment of lymphomas. Used in combination with other antineoplastics in established chemotherapeutic protocols.

Contraindications

History of drug-induced myelosuppression; immunization procedures; pregnancy (category D) particularly during first trimester, lactation. Safe use in infants not established.

Cautious Use

Impaired renal or hepatic function, elderly; neurologic disease; gout, drug-induced myelosuppression.

Route & Dosage

Leukemias
Adult/Child: IV 100–200 mg/m² by continuous infusion over 24 h SC 1 mg/kg 1–2 times/wk Intrathecal 5–75 mg once q4d or once/d for 4 d

Renal Impairment
Serum Cr of 1.5–1.9 mg/dL (or from baseline of 0.5–1.2 mg/dL): reduce to 1 g/m²/dose. Serum Cr of 2 or more (or >1.2 mg/dL change): do not exceed 100 mg/m²/d.

Administration

Intrathecal

For intrathecal injection, reconstitute with an isotonic, buffered diluent without preservatives. Follow manufacturer's recommendations.

Intravenous

PREPARE: Direct: Reconstitute with bacteriostatic water for injection (without benzyl alcohol for neonates) as follows: add 5 mL to the 100-mg vial to yield 20 mg/mL; add 10 mL to the 500 mg vial to yield 50 mg/mL. IV Infusion: May be further diluted with 100 mL or more of D5W or NS.

ADMINISTER: Direct: Give at a rate of 100 mg or a fraction thereof over 3 min. IV Infusion: Give over 30 min or longer depending on the total volume of IV solution to be infused.

INCOMPATIBILITIES Solution/additive: Fluorouracil, gentamicin, heparin, hydrocortisone, insulin, nafcillin, oxacillin, penicillin G. Y-site: Allopurinol, amphotericin B cholesteryl sulfate complex, gallium, ganciclovir, lansoprazole, TPN.

Store cytarabine in refrigerator until reconstituted. Reconstituted solutions may be stored at 15°–30° C (59°–86° F) for 48 h. Discard solutions with a slight haze.

Adverse Effects (≥1%)

Body as a Whole: Weight loss, sore throat, fever, thrombophlebitis and pain at injection site; pericarditis, bleeding (any site), pneumonia. Potentially carcinogenic and mutagenic. GI: Nausea, vomiting, diarrhea, stomatitis, oral or anal inflammation or ulceration, esophagitis, anorexia, hemorrhage, hepatotoxicity, jaundice. Hematologic: Leukopenia, thrombocytopenia, anemia, megaloblastosis, myelosuppression (reversible); transient hyperuricemia. CNS: Headache, neurotoxicity; peripheral neuropathy, brachial plexus neuropathy, personality change, neuritis, vertigo, lethargy, somnolence, confusion. Skin: Rash, erythema, freckling, cellulitis, skin ulcerations, pruritus, urticaria, bulla formation, desquamation. Special Senses: Conjunctivitis, keratitis, photophobia. Urogenital: Renal dysfunction, urinary retention.

Interactions

Drug: GI toxicity may decrease digoxin absorption; decreases aminoglycosides activity against Klebsiella pneumoniae.

Pharmacokinetics

Peak: 20–60 min SC. Distribution: Crosses blood-brain barrier and placenta. Metabolism: In liver. Elimination: 80% in urine in 24 h. Half-Life: 1–3 h.

Nursing Implications

Assessment & Drug Effects

Inspect patient's mouth before the administration of each dose. Toxicity necessitating dosage alterations almost always occurs. Report adverse reactions immediately.
Lab tests: Hct and platelet counts and total and differential leukocyte counts should be evaluated daily during initial therapy. Serum uric acid and hepatic function tests should be performed at regular intervals throughout treatment period.
Hyperuricemia due to rapid destruction of neoplastic cells may accompany cytarabine therapy. A regimen that includes a uricosuric agent such as allopurinol, urine alkalinization, and adequate hydration may be started. To reduce potential for urate stone formation, fluids are forced in excess of 2 L, if tolerated. Consult physician.
Monitor I&O ratio and pattern.
Monitor body temperature. Be alert to the most subtle signs of infection, especially low-grade fever, and report promptly.
When platelet count falls below 50,000/mm³ and polymorphonuclear leukocytes to below 1000/mm³, therapy may be suspended. WBC nadir is usually reached in 5–7 d after therapy has been stopped. Therapy is restarted with appearance of bone marrow recovery and when preceding cell counts are reached.
Provide good oral hygiene to diminish adverse effects and chance of superinfection. Stomatitis and cheilosis usually appear 5–10 d into the therapy.

Patient & Family Education

Report promptly protracted vomiting or signs of nephrotoxicity (see Appendix F).
Flu-like syndrome occurs usually within 6–12 wk after drug administration and may recur with successive therapy. Report chills, fever, achy joints and muscles.
Report any S&S of superinfection (see Appendix F).

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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