cytarabine

Absorption: Absorption occurs from SUBQ sites, but blood levels are lower than with IV administration; IT administration results in negligible systemic exposure.

Distribution: Widely distributed; IV- and SUBQ-administered cytarabine crosses the blood-brain barrier but not in sufficient quantities.

Metabolism/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, SUBQ: 1–3 hr; IT: 100–236 hr.

Time/Action Profile ⬆ ⬇

(IV, SUBQ—effects on WBCs; IT—levels in CSF)

ROUTE	ONSET	PEAK	DURATION
SUBQ, IV (1st phase)	24 hr	7–9 days	12 days
SUBQ, IV (2nd phase)	15–24 days	15–24 days	25–34 days
IT	rapid	5 hr	14–28 days

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Active meningeal infection (IT only);OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Active infection;
↓bone marrow reserve;
Renal impairment;
Hepatic impairment;
Rep: Women of reproductive potential.

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema

Derm: alopecia, rash

EENT: corneal toxicity (high dose), hemorrhagic conjunctivitis (high dose), visual disturbances (including blindness)

GI: nausea, vomiting, GI ulceration (high dose), HEPATOTOXICITY, stomatitis

GU: sterility, urinary incontinence

Hemat:

(less with IT use)

anemia, leukopenia, thrombocytopenia

Metab: hyperuricemia

Neuro:

abnormal gait, CHEMICAL ARACHNOIDITIS, CNS dysfunction (high dose), confusion, drowsiness, headache

Resp: PULMONARY EDEMA (HIGH DOSE)

Misc: cytarabine syndrome, fever

Interactions ⬆ ⬇

Drug-drug:

↑bone marrow depression with other antineoplastics or radiation therapy.
↑risk of cardiomyopathy when used in high-dose regimens with cyclophosphamide.
May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions.
May ↓ absorption of digoxin tablets.
May ↓ the efficacy of gentamicin when used to treat
Klebsiella pneumoniae
infections.
Recent treatment with asparaginase may ↑ risk of pancreatitis.
↑risk of neurotoxicity with concurrently administered IT antineoplastics (IT only).

Route/Dosage ⬆ ⬇

Dose regimens vary widely
IV (Adults ): Induction dose: 200 mg/m²/day for 5 days every 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 every 12 hr for up to 12 doses.
SC (Adults ): Maintenance: 1–1.5 mg/kg every 1–4 wk.
(Adults ): Usual dose = 30 mg/m² every 4 days; range = 5–75 mg/m² once daily for 4 days or every 4 days until CNS findings normalize, followed by one additional treatment.

Availability ⬆ ⬇

(Generic available)

Solution for injection: 20 mg/mL; 100 mg/mL
In combination with: daunorubicin (Vyxeos). See Appendix [not included in this PDA edition].

Assessment ⬆ ⬇

Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
Monitor intake and output ratios and daily weights. Report significant changes in totals.
Monitor for symptoms of gout (increased uric acid, joint pain, edema). Encourage patient to drink at least 2 L of fluid each day. Allopurinol may decrease uric acid levels. Alkalinization of urine may increase excretion of uric acid.
Assess nutritional status. Nausea and vomiting may occur within 1 hr of administration, especially if IV dose is administered rapidly, less severe if medication is infused slowly. Administering an antiemetic prior to and periodically throughout therapy and adjusting diet as tolerated may help maintain fluid and electrolyte balance and nutritional status.
Monitor patient for development of cytarabine (fever, myalgia, bone pain, chest pain, maculopapular rash, conjunctivitis, malaise), which usually occurs 6–12 hr following administration. Corticosteroids may be used for treatment or prevention. If patient responds to corticosteroids, continue cytarabine and corticosteroids.
Assess patient for respiratory distress and pulmonary edema. Occurs with high doses rarely; may be fatal.
Monitor patient for signs of anaphylaxis (rash, dyspnea, swelling). Epinephrine, corticosteroids, and resuscitation equipment should be readily available.
CSF flow should be evaluated prior to IT therapy. Administer directly into CSF via an intraventricular reservoir or by direct injection into the lumbar sac slowly over 1–5 min. Following administration by lumbar puncture, patient should lie flat for 1 hr. Chemical arachnoiditis (nausea, vomiting, headache, fever, back pain, CSF pleocytosis and neck rigidity, neck pain, or meningism) is an expected side effect of IT cytarabine. Incidence and severity of symptoms may be decreased with coadministration of dexamethasone. 4 mg bid, PO or IV, for 5 days beginning on day of injection.
- Monitor patients receiving IT therapy continuously for the development of neurotoxicity (myelopathy, personality changes, dysarthria, ataxia, confusion, somnolence, coma). If neurotoxicity develops, decrease amount of subsequent doses and discontinue if neurotoxicity persists. Risk may be increased if cytarabine is administered intrathecally and IV within a few days.

Lab Test Considerations:

Monitor CBC with differential and platelet count prior to and frequently during therapy. Leukocyte counts begin to drop within 24 hr of administration. The initial nadir occurs in 7–9 days. After a small ↑ in the count, the second, deeper nadir occurs 15–24 days after administration. Platelet counts begin to ↓ 5 days after a dose, with a nadir at 12–15 days. Leukocyte and platelet counts usually begin to ↑ 10 days after the nadirs. Therapy is usually withdrawn if leukocyte count is <1000/mm³ or platelet count is <50,000/mm³. Bone marrow aspirations are recommended every 2 wk until remission occurs.
- Monitor renal (BUN and serum creatinine) and hepatic function (AST, ALT, bilirubin, alkaline phosphatase, and LDH) prior to and routinely during therapy.
- May cause ↑ uric acid concentrations.

Implementation ⬆ ⬇

Reconstitute IT doses with preservative-free 0.9% NaCl or autologous spinal fluid. Use immediately to prevent bacterial contamination.
Instruct patient to lie flat for 1 hr following IT injection. Monitor for immediate toxic reactions.

Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, calculations, and infusion pump settings.
Do not confuse high-dose and regular therapy. Fatalities have occurred with high-dose therapy.
Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers.
- May be given SUBQ, direct IV, intermittent IV, continuous IV, or IT.

IV Administration:

Diluent: Administer undiluted.Concentration: 100 mg/mL.
Intermittent Infusion: Diluent: May be further diluted in 0.9% NaCl, D5W, D10W, D5/0.9% NaCl, Ringer’s solution, LR, or D5/LR.Concentration: Dilute doses in 100 mL of diluent.
Rate: Infuse over 15–30 min.
Rate and concentration for IV infusion are ordered individually.

Patient/Family Teaching ⬆ ⬇

Caution patient to avoid crowds and persons with known infections. Report symptoms of infection (fever, chills, cough, hoarseness, sore throat, lower back or side pain, painful or difficult urination) immediately.
Instruct patient to report unusual bleeding. Advise patient of thrombocytopenia precautions (use soft toothbrush and electric razor, avoid falls, do not drink alcoholic beverages or take medication containing aspirin or NSAIDs; may precipitate gastric bleeding).
Instruct patient to inspect oral mucosa for redness and ulceration. If mouth sores occur, advise patient to use sponge brush and rinse mouth with water after eating and drinking. Stomatitis may require treatment with opioid analgesics.
Instruct patient not to receive any vaccinations without advice of health care professional.
Rep: Advise patient that this medication may have teratogenic effects. Contraception should be used during therapy and for at least 4 mo after therapy is concluded.
Emphasize the need for periodic lab tests to monitor for side effects.
Inform patient about the expected side effects (headache, nausea, vomiting, fever) and about early signs of neurotoxicity. Instruct patient to notify health care professional if these signs occur.

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇