Pronunciation:

(sye TARE a been)

U.S. Brand Names:

Synonyms:

Generic Available:

Canadian Brand Names:

Use:

Pregnancy Risk Factor:

Pregnancy Implications:

Lactation:

Contraindications:

Warnings/Precautions:

Adverse Reactions:

>10%:

Central nervous system: Fever (>80%)

Dermatologic: Alopecia

Gastrointestinal: Nausea, vomiting, diarrhea, and mucositis which subside quickly after discontinuing the drug; GI effects may be more pronounced with divided I.V. bolus doses than with continuous infusion

Hematologic: Myelosuppression; neutropenia and thrombocytopenia are severe, anemia may also occur

Onset: 4-7 days

Nadir: 14-18 days

Recovery: 21-28 days

Hepatic: Hepatic dysfunction, mild jaundice, transaminases increased (acute)

Ocular: Tearing, ocular pain, foreign body sensation, photophobia, and blurred vision may occur with high-dose therapy; ophthalmic corticosteroids usually prevent or relieve the condition

1% to 10%:

Cardiovascular: Thrombophlebitis, cardiomegaly

Central nervous system: Dizziness, headache, somnolence, confusion, malaise; a severe cerebellar toxicity occurs in about 8% of patients receiving a high dose (>36-48 g/m²/cycle); it is irreversible or fatal in about 1%

Dermatologic: Skin freckling, itching, cellulitis at injection site; rash, pain, erythema, and skin sloughing of the palmar and plantar surfaces may occur with high-dose therapy. Prophylactic topical steroids and/or skin moisturizers may be useful.

Genitourinary: Urinary retention

Neuromuscular & skeletal: Myalgia, bone pain

Respiratory: Syndrome of sudden respiratory distress, including tachypnea, hypoxemia, interstitial and alveolar infiltrates progressing to pulmonary edema, pneumonia

<1%: Increases in amylase and lipase levels; isolated cases of pancreatitis have been reported; dysphagia (reported with intrathecal use); peripheral neuropathy, neuritis; accessory nerve paralysis (reported with intrathecal use); diplopia (reported with intrathecal use); cough, hoarseness (reported with intrathecal use); aphonia (reported with intrathecal use)

Overdosage/Toxicology:

Drug Interactions:

Methotrexate: When administered prior to cytarabine, may enhance the efficacy and toxicity of cytarabine. Some combination treatment regimens (eg, hyper-CVAD) have been designed to take advantage of this interaction.

Decreased effect of gentamicin, flucytosine; decreases digoxin oral tablet absorption

Increased toxicity: Alkylating agents and radiation; purine analogs

Stability:

Powder for reconstitution: Store intact vials of powder at room temperature 15°C to 30°C (59°F to 86°F). Reconstitute with bacteriostatic water for injection. Reconstituted solutions are for up to 8 days at room temperature.

Solution: Prior to dilution, store at room temperature, 15°C to 30°C (59°F to 86°F); protect from light.

Further dilution in D5W or NS is stable for 8 days at room temperature (25°C). Intrathecal solutions in 3-20 mL lactated Ringer's are stable for 7 days at room temperature (30°C); however, should be used within 24 hours due to sterility concerns.

Standard I.V. infusion dilution: Dose/250-1000 mL D5W or NS

Standard intrathecal dilutions: Dose/3-5 mL lactated Ringer's ± methotrexate (12 mg) ± hydrocortisone (15-50 mg)

Note: Solutions containing bacteriostatic agents should not be used for the preparation of either high doses or intrathecal doses of cytarabine; may be used for I.M., SubQ, and low-dose (100-200 mg/m²) I.V. solution. High-dose regimens are usually administered by I.V. infusion over 1-3 hours or as I.V. continuous infusion; for I.T. use, reconstitute with preservative free saline or preservative free lactated Ringer's solution

Compatibility:

Y-site administration: Compatible: Amifostine, amsacrine, aztreonam, cefepime, chlorpromazine, cimetidine, cladribine, dexamethasone sodium phosphate, diphenhydramine, doxorubicin liposome, droperidol, etoposide phosphate, famotidine, filgrastim, fludarabine, furosemide, gatifloxacin, gemcitabine, gentamicin, granisetron, heparin, hydrocortisone sodium succinate, hydromorphone, idarubicin, linezolid, lorazepam, melphalan, methotrexate, methylprednisolone sodium succinate, metoclopramide, morphine, ondansetron, paclitaxel, piperacillin/tazobactam, prochlorperazine edisylate, promethazine, propofol, ranitidine, sargramostim, sodium bicarbonate, teniposide, thiotepa, vinorelbine. Incompatible: Allopurinol, amphotericin B cholesteryl sulfate complex, ganciclovir

Compatibility in syringe: Compatible: Metoclopramide

Compatibility when admixed: Compatible: Corticotropin, dacarbazine, daunorubicin with etoposide, etoposide, hydroxyzine, lincomycin, methotrexate, mitoxantrone, ondansetron, potassium chloride, sodium bicarbonate, vincristine. Incompatible: Fluorouracil, heparin, insulin (regular), nafcillin, oxacillin, penicillin G sodium. Variable (consult detailed reference): Gentamicin, hydrocortisone sodium succinate, methylprednisolone sodium succinate

Mechanism of Action:

Pharmacodynamics/Kinetics:

Distribution: Vd: Total body water; widely and rapidly since it enters the cells readily; crosses blood-brain barrier with CSF levels of 40% to 50% of plasma level

Metabolism: Primarily hepatic; aracytidine triphosphate is the active moiety; about 86% to 96% of dose is metabolized to inactive uracil arabinoside

Half-life elimination: Initial: 7-20 minutes; Terminal: 0.5-2.6 hours

Excretion: Urine (~80% as metabolites) within 24-36 hours

Dosage:

Remission induction:

I.V.: 100-200 mg/m²/day for 5-10 days; a second course, beginning 2-4 weeks after the initial therapy, may be required in some patients.

I.T.: 5-75 mg/m² every 2-7 days until CNS findings normalize; or age-based dosing:

<1 year: 20 mg

1-2 years: 30 mg

2-3 years: 50 mg

>3 years: 75 mg

Remission maintenance:

I.V.: 70-200 mg/m²/day for 2-5 days at monthly intervals

I.M., SubQ: 1-1.5 mg/kg single dose for maintenance at 1- to 4-week intervals

High-dose therapies:

Doses as high as 1-3 g/m² have been used for refractory or secondary leukemias or refractory non-Hodgkin's lymphoma.

Doses of 1-3 g/m² every 12 hours for up to 12 doses have been used

Bone marrow transplant: 1.5 g/m² continuous infusion over 48 hours

Hemodialysis: Supplemental dose is not necessary.

Peritoneal dialysis: Supplemental dose is not necessary.

Dosage adjustment in hepatic impairment: Dose may need to be adjusted since cytarabine is partially detoxified in the liver.

Administration:

I.V. may be administered either as a bolus, IVPB (high doses of >500 mg/m²), or continuous intravenous infusion (doses of 100-200 mg/m²) high-dose regimens are usually administered by I.V. infusion over 1-3 hours or as I.V. continuous infusion

I.V. doses of 1.5 g/m² may produce conjunctivitis which can be ameliorated with prophylactic use of corticosteroid (0.1% dexamethasone) eye drops. Dexamethasone eye drops should be administered at 1-2 drops every 6 hours during and for 2-7 days after cytarabine is done.

Monitoring Parameters:

Patient Education:

Nursing Implications:

Additional Information:

Pyridoxine has been administered on days of high-dose Ara-C therapy for prophylaxis of CNS toxicity.

Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Mental Health: Effects on Mental Status:

Mental Health: Effects on Psychiatric Treatment:

Oncology: Emetic Potential:

Oncology: Vesicant:

Oncology: Bone Marrow Comments:

Oncology: Bone Marrow - High Dose:

Oncology: Bone Marrow - Unique Toxicity:

Central nervous system: Cerebellar toxicity which includes nystagmus, dysarthria, disdiadochokinesis, slurred speech; cerebral toxicity which includes somnolence, confusion

Dermatologic: Rash, desquamation may occur

Gastrointestinal: Severe nausea and vomiting, mucositis, diarrhea, ageusia

Ocular: Photophobia, excessive tearing, blurred vision, local discomfort, chemical conjunctivitis, optic neuropathy, visual loss

Respiratory: Noncardiogenic pulmonary edema (onset 22-27 days following completion of therapy)

Miscellaneous: Anosmia

Dosage Forms:

Injection, powder for reconstitution: 100 mg, 500 mg, 1 g, 2 g

Injection, solution: 20 mg/mL (5 mL, 25 mL, 50 mL); 100 mg/mL (20 mL)

International Brand Names: