cytarabine (Rx)

1-10%

Anorexia

Nausea

Vomiting

Diarrhea

Oral/anal inflammation

Thrombophlebitis

Bleeding

Myelosuppression

Rash

Fever

Hepatic dysfunction

Frequency Not Defined

Headache

Neuropathy

Chest pain

Pericarditis

Pneumonia

Anemia

Bleeding

Leukopenia

Thrombocytopenia

Kidney disease

Infectious disease

Sepsis

"Cytarabine syndrome": fever, myalgia, bone pain, rash, conjunctivitis, malaise

Skin ulcers

Cellulitis

Urinary retention

Neuritis

Jaundice

Anaphylaxis

Contraindications

Hypersensitivity

Liposomal cytarabine: active meningeal infection

Cautions

Potent bone marrow suppression

Severe and at times fatal CNS, GI, and pulmonary toxicity

Cardiomyopathy with subsequent death reported following experimental high dose therapy with cytarabine in combination with cyclophosphamide when used for bone marrow transplant preparation

Do not use benzyl alcohol-containing solutions IT or in neonates

Avoid pregnancy

Liposomal IT administration

• CSF flow assessment should be considered before treatment is started Blockage to CSF flow may increase risk of neurotoxicity due to increased serum concentrations
• To reduce incidence of arachnoiditis, administer dexamethasone concurrently
• Hydrocephalus has also been reported, possibly precipitated by arachnoiditis
• Infectious meningitis may be associated with IT drug administration
• Following IT administration, CNS toxicity, including persistent extreme somnolence, hemiplegia, visual disturbances including blindness which may be total and permanent, deafness, cranial nerve palsies, and visual disturbances including blindness which may be total and permanent, have been reported
• Symptoms and signs of peripheral neuropathy (eg, pain, numbness, paresthesia, weakness, impaired bowel and bladder control) observed; in some cases, these signs and symptoms have been reported as Cauda Equina Syndrome

Pregnancy Category: D

Lactation: not known if excreted in breast milk, avoid

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Metabolite cytarabine-5'-triphosphate inhibits DNA polymerase during S phase

Absorption

Systemic Exposure after IT: negligible

Peak plasma time: 20-60 min

Peak CSF time (IT): 60 min

Peak CSF concentration (IT): 30-50 mcg/mL

Distribution

Protein bound: 13%

Metabolism

Metabolism: liver (major), kidneys (minor); neglible following IT administration

Metabolites: cytarabine-5'-triphosphate (ara-CTP)

Elimination

Half-life: 1-3 hr

Half-life (CSF after IT): 5.9-82.4 hr

CSF clearance rate: 0.24 mL/min

Excretion: urine

IV Incompatibilities

Additive: fluorouracil, gentamicin(?), heparin, hydrocortisone sodium succinate(?), insulin, methylprednisolone(?), nafcillin, oxacillin, penicillin G sodium

Y-site: allopurinol, amphotericin B cholesteryl SO4, ganciclovir

IV Compatibilities

Solution: compatible with most common IV fluids

Additive: corticotropin, daunorubicin/etoposide, hydroxyzine, lincomycin, methotrexate, mitoxantrone, ondansetron, KCl, NaHCO3, vincristine

Syringe: metoclopramide

Y-site: amifostine, amsacrine, aztreonam, cefepime, chlorpromazine, cimetidine, cladribine, dexamethasone, diphenhydramine, doxorubicin liposomal, droperidol, etoposide PO4, famotidine, filgrastim, fludarabine, furosemide, gatifloxacin, gemcitabine, gentamicin, granisetron, heparin, hydrocortisone, hydromorphone, idarubicin, linezolid, lorazepam, melphalan, methotrexate, methylprednisolone, metoclopramide, morphine SO4, ondansetron, paclitaxel, piperacillin/tazobactam, prochlorperazine, promethazine, propofol, ranitidine, sargramostim, Na Bicarb, teniposide, thiotepa, vinorelbine

IV Preparation

Reconstitute vials in BWI containing benzyl alcohol 0.945% as follows (CAUTION: Do not use benzyl alcohol for intrathecal inj)

100 mg vial: add 5 mL diluent to 20 mg/mL

500 mg vial: add 10 mL diluent to 50 mg/mL

1 g vial: add 10 mL diluent to 100 mg/mL

2 g vial: add 20 mL diluent to 100 mg/mL

IV Administration

Rapid IV, infusion over 1-3 hr, or SC intrathecal

Has been administered by IM & continuous SC infusion

Storage

Store intact vials at controlled room temp