cytarabine (sye-tare-a-been) cytosine arabinoside, Cytosar, Cytosar- U

 Indications

IV: Used mainly in combination chemotherapeutic regimens

for the treatment of leukemias and non-Hodgkin’s

lymphomas. IT: Prophylaxis and treatment of meningeal

leukemia.

Action

Inhibits DNA synthesis by inhibiting DNA polymerase

(cell-cycle S-phase–specific). Therapeutic Effects:

Death of rapidly replicating cells, particularly

malignant ones.

Pharmacokinetics

Absorption: Absorption occurs from subcut sites,

but blood levels are lower than with IV administration;

IT administration results in negligible systemic exposure.

Distribution: Widely distributed; IV- and subcut-administered

cytarabine crosses the blood-brain barrier

but not in sufficient quantities. Crosses the placenta.

Metabolism and Excretion: Metabolized mostly

by the liver; 10% excreted unchanged by the kidneys.

Metabolism to inactive drug in the CSF is negligible because

the enzyme that metabolizes it is present in very

low concentrations in the CSF.

Half-life: IV, subcut—1–3 hr; IT—100–236 hr.

TIME/ACTION PROFILE (IV, subcut—effects

on WBCs; IT—levels in CSF)

ROUTE ONSET PEAK DURATION

Subcut, IV

(1st

phase)

24 hr 7–9 days 12 days

Subcut, IV

(2nd

phase)

15–24 days 15–24 days 25–34 days

IT rapid 5 hr 14–28 days

Contraindications/Precautions

Contraindicated in: Hypersensitivity; OB, Lactation:

Pregnancy or lactation; Active meningeal infection

(IT only).

Use Cautiously in: Active infections;pbone marrow

reserve; Renal/hepatic impairment; Other chronic

debilitating illnesses; Rep: Women of reproductive potential.

Adverse Reactions/Side Effects

CNS: CNS dysfunction (high dose), confusion, drowsiness,

headache. EENT: corneal toxicity (high dose),

hemorrhagic conjunctivitis (high dose), visual disturbances

(including blindness). Resp: PULMONARY

EDEMA (high dose). CV: edema. GI: nausea, vomiting,

hepatotoxicity, severe GI ulceration (high dose), stomatitis.

GU: urinary incontinence. Derm: alopecia, rash.

Endo: sterility. Hemat: (less with IT use)—anemia,

leukopenia, thrombocytopenia.Metab: hyperuricemia.

Neuro: Intrathecal only—CHEMICAL

ARACHNOIDITIS, abnormal gait. Misc: cytarabine syndrome,

fever.

Interactions

Drug-Drug:qbone marrow depression with other

antineoplastics or radiation therapy.qrisk of cardiomyopathy

when used in high-dose regimens with cyclophosphamide.

Maypantibody response to livevirus

vaccines andqrisk of adverse reactions. Mayp

absorption of digoxin tablets. Maypthe efficacy of

gentamicin when used to treat Klebsiella pneumoniae

infections. Recent treatment with asparaginase

mayqrisk of pancreatitis.qneurotoxicity with concurrently

administered IT antineoplastics (IT only).

Route/Dosage

Dose regimens vary widely.

IV (Adults): Induction dose—200 mg/m2/day for 5

days q 2 wk as a single agent or 2–6 mg/kg/day (100–

200 mg/m2/day) as a single daily dose or in 2–3 divided

doses for 5–10 days or until remission occurs as

part of combination chemotherapy. Maintenance—

70–200 mg/m2/day for 2–5 days monthly. Refractory

leukemias/lymphomas—3 g/m2 q 12 hr for up to 12

doses.

Subcut (Adults): Maintenance—1–1.5 mg/kg q 1–

4 wk.

IT (Adults): Usual dose30 mg/m2 every 4 days;

range5–75 mg/m2 once daily for 4 days or every 4

days until CNS findings normalize, followed by one additional

treatment.

Availability (generic available)

Powder for injection: 100 mg, 500 mg, 1 g, 2 g. Solution

for injection: 20 mg/mL, 100 mg/mL.