cytarabine

cytarabine /cy·tar·a·bine/ (ara-C) (si-tar´ah-bēn) an antimetabolite that inhibits DNA synthesis and hence has antineoplastic properties; used in the treatment of acute myelogenous and other types of leukemia and of meningitis associated with leukemia or lymphoma.

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cyt·ar·a·bine (s-tr-bn)

n.

See cytosine arabinoside.

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cytarabine

[siter′əbēn]

an antineoplastic agent. Also called arabinosylcytosine, ARA-C, cytosine arabinoside.

indications It is prescribed in the treatment of acute and chronic myelocytic leukemia, acute lymphocytic leukemia, and erythroleukemia.

contraindication Known hypersensitivity to this drug prohibits its use.

adverse effects The most serious adverse reactions are bone marrow depression, stomatitis, phlebitis, liver toxicity, fever, and GI disturbances.

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cytarabine [si-tar´ah-bēn]

an antimetaboliteantineoplastic agent that inhibits DNA polymerase and thus inhibits DNA synthesis during a specific phase of the cell cycle. Administered intravenously to treat acute myelogenous and other types of leukemia. It is also injected intrathecally to treat meningitis associated with leukemia or lymphoma. Called also cytosine arabinoside.

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cytarabine

an antimetabolite that inhibits DNA synthesis, and hence has antineoplastic and antiviral properties. Called also cytosine arabinoside, arabinosyl cytosine, ara-C.

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cytarabine Warning - Hazardous drug!

Cytosar (CA), Cytosar-U, DepoCyt

Pharmacologic class: Antimetabolite, pyrimidine analog

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Boxed Warning

• Drug should be given only by physicians experienced in cancer chemo-therapy. For induction therapy, patients should be in facility with adequate resources to monitor drug tolerance and treat drug toxicity. Main toxic effect is bone marrow suppression with leukopenia, thrombocytopenia, and anemia. Less serious toxicities include nausea, vomiting, diarrhea, abdominal pain, oral ulcers, and hepatic dysfunction.
• Prescriber must weigh possible benefit against known toxic effects and should be familiar with complete package insert information.
• Give DepoCyt (liposomal injection) only under supervision of physician experienced with intrathecal cancer chemotherapy, in facility with adequate diagnostic and treatment resources. In all clinical studies, chemical arachnoiditis (manifested mainly by nausea, vomiting, headache, and fever) was common adverse event; unless treated, it may be fatal. Patients receiving DepoCyt should receive dexamethasone concurrently to mitigate arachnoiditis symptoms.

Action

Unclear. Cytotoxic effect may stem from inhibition of DNA polymerase by drug's active metabolite.

Availability

Injection (conventional form): 20 mg

Liposomal injection for intrathecal use (sustained-release): 50 mg/5-ml vial

Powder for injection (conventional form): 100 mg, 500 mg, 1g, 2 g

⊘Indications and dosages

➣ To induce remission of acute nonlymphocytic leukemia

Adults: Injection (conventional form) - 100 mg/m²/day by continuous I.V. infusion on days 1 through 7, or 100 mg/m² I.V. q 12 hours on days 1 through 7, given with other antineoplastics

➣ Meningeal leukemia

Adults: Injection (conventional form) - 5 to 75 mg/m²/day intrathecally for 4 days, or once q 4 days. Most common dosage is 30 mg/m² q 4 days until cerebrospinal fluid is normal.

➣ Lymphomatous meningitis

Adults: Liposomal injection - 50 mg intrathecally q 14 days for two doses (at weeks 1 and 3); then q 14 days for three doses (at weeks 5, 7, and 9), with one additional dose at week 13; then q 28 days for four doses

Contraindications

• Hypersensitivity to drug
• Active meningeal infection (liposomal form)

Precautions

Use cautiously in:
• renal or hepatic disease, active infection, decreased bone marrow reserve, other chronic illnesses
• pregnant or breastfeeding patients.

Administration

• Follow facility procedures for safe handling, administration, and disposal of chemotherapeutic drugs.
• For I.V. injection, reconstitute each 100 mg with 5 ml of diluent (if necessary), and give each 100-mg dose over 1 to 3 minutes. For I.V. infusion, dilute further with 50 to 100 ml of dextrose 5% in water or normal saline solution, and infuse over 30 minutes to 24 hours (depending on dosage and concentration).
• Be aware that conventional and liposomal forms can be administered inthrathecally.
☞ Don't use intrathecal route for formulations containing benzyl alcohol.
• When giving conventional form intrathecally, reconstitute with autologous spinal fluid or preservative-free normal saline solution for injection. Use immediately.
• Patients receiving intrathecal cytarabine should be treated concurrently with dexamethasone to mitigate symptoms of chemical arachnoiditis.

Route	Onset	Peak	Duration
I.V.	Unknown	Unknown	Unknown
Intrathecal	Rapid	5 hr	14-28 hr

Adverse reactions

CNS: malaise, dizziness, headache, neuritis, neurotoxicity, chemical arachnoiditis

CV: chest pain, thrombophlebitis

EENT: conjunctivitis

GI: nausea, vomiting, diarrhea, abdominal pain, anal ulcers, esophagitis, esophageal ulcers, oral ulcers (in 5 to 10 days), anorexia, bowel necrosis

GU: urinary retention, renal dysfunction

Hematologic: anemia, megaloblastosis, reticulocytopenia, leukopenia, thrombocytopenia

Hepatic: hepatic dysfunction

Metabolic: hyperuricemia

Musculoskeletal: muscle ache, bone pain

Respiratory: pneumonia, shortness of breath

Skin: rash, pruritus, freckling, skin ulcers, urticaria, alopecia

Other: flulike symptoms, edema, infection, fever, cellulitis at injection site, anaphylaxis, infection (mild to fatal)

Interactions

Drug-drug. Digoxin: decreased digoxin blood level

Fluorocytosine: decreased fluorocytosine blood level

Gentamicin: decreased gentamicin effects

Drug-diagnostic tests. Hemoglobin, platelets, red blood cells, reticulocytes, white blood cells: decreased values

Megaloblasts, uric acid: increased levels

Patient monitoring

• Observe for signs and symptoms of cytarabine syndrome (malaise, fever, muscle ache, bone pain, occasional chest pain, maculopapular rash, and conjunctivitis).
☞ When giving liposomal form, assess for signs and symptoms of chemical arachnoiditis, such as neck rigidity and pain, nausea, vomiting, headache, fever, and back pain.
• Monitor liver function test results, CBC with differential, platelet count, blood urea nitrogen, and serum creatinine and uric acid levels.
☞ Observe closely for signs and symptoms of infection, which could become severe and fatal.

Patient teaching

☞ Tell patient to contact prescriber immediately if he develops signs or symptoms of infection, cytarabine syndrome (malaise, fever, muscle ache, bone pain, chest pain, rash, eye infection), or chemical arachnoiditis (neck rigidity or pain, nausea, vomiting, headache, fever, or back pain).
☞ Tell patient that drug makes him more susceptible to infection. Advise him to avoid crowds and exposure to illness.
• Advise patient to increase fluid intake, to promote uric acid excretion.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

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cytarabine

AraC, cytosine arabinoside Oncology An antimetabolite analogue of deoxycytidine, used synergistically with antifolates, alkylating agents, and cis-platinum to treat AML Pharmacokinetics Poorly absorbed–±20% absorbed orally, better IV; T_{1 ⁄ 2}, ±2.5 hrs; 90% metabolized to the inactive arabinosyl uracil Side effects N&V, myelosuppression; in high doses, cerebral dysfunction, ataxia