Cytosar


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cytarabine

(sye-tare-a-been) ,

cytosine arabinoside

(trade name),

Cytosar

(trade name),

Cytosar-U

(trade name),

DepoCyt

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: antimetabolites
Pregnancy Category: D

Indications

Intravenous: Used mainly in combination chemotherapeutic regimens for the treatment of leukemias and non-Hodgkin’s lymphomas. Intrathecal: Treatment of lymphomatous meningitis.

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)

ROUTEONSETPEAKDURATION
Subcut, IV (1st phase)24 hr7–9 days12 days
Subcut, IV (2nd phase)15–24 days15–24 days25–34 days
ITrapid5 hr14–28 days

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Obstetric / Lactation: Pregnancy or lactation;Active meningeal infection (IT only).
Use Cautiously in: Active infections;↓ bone marrow reserve;Renal/hepatic impairment;Other chronic debilitating illnesses; Obstetric: Patients with childbearing potential.

Adverse Reactions/Side Effects

Central nervous system

  • CNS dysfunction (high dose)
  • confusion
  • drowsiness
  • headache

Ear, Eye, Nose, Throat

  • corneal toxicity (high dose)
  • hemorrhagic conjunctivitis (high dose)
  • visual disturbances (including blindness)

Respiratory

  • pulmonary edema (high dose) (life-threatening)

Cardiovascular

  • edema

Gastrointestinal

  • nausea (most frequent)
  • vomiting (most frequent)
  • hepatotoxicity
  • severe GI ulceration (high dose)
  • stomatitis

Genitourinary

  • urinary incontinence

Dermatologic

  • alopecia
  • rash

Endocrinologic

  • sterility

Hematologic

    (less with IT use):
  • anemia (most frequent)
  • leukopenia (most frequent)
  • thrombocytopenia (most frequent)

Metabolic

  • hyperuricemia

Neurologic

    Intrathecal only:
  • chemical arachnoiditis (life-threatening)
  • abnormal gait

Miscellaneous

  • cytarabine syndrome
  • fever

Interactions

Drug-Drug interaction

↑ 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.↑ neurotoxicity with concurrently administered IT antineoplastics (IT only).

Route/Dosage

Dose regimens vary widely
Intravenous (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.
Subcutaneous (Adults) Maintenance—1–1.5 mg/kg q 1–4 wk.
Intrathecal (Adults) Depo Cyt Induction—50 mg (intraventricular or lumbar puncture) q 14 days for 2 doses (weeks 1 and 3); consolidation—50 mg (intraventricular or lumbar puncture) q 14 days for 3 doses (weeks 5, 7, and 9), followed by 1 additional dose at week 13; maintenance—50 mg (intraventricular or lumbar puncture) q 28 days for 4 doses (weeks 17, 21, 25, and 29). If drug-related neurotoxicity occurs, dose should be reduced to 25 mg or discontinued (dexamethasone 4 mg PO/IV twice daily for 5 days should be started concurrently with IT cytarabine).

Availability (generic available)

Powder for injection: 100 mg, 500 mg, 1 g, 2 g
Solution for injection: 20 mg/mL, 100 mg/mL
Sustained-release liposome injection for IT use: 10 mg/mL

Nursing implications

Nursing 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 or ara-C syndrome (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.
  • Intrathecal: CSF flow should be evaluated prior to IT therapy. Allow DepoCyt to warm to room temperature. Gently agitate or invert to re-suspend particles; do not shake. 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 thrombocyte 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 creatinine) and hepatic function (AST, ALT, bilirubin, alkaline phosphatase, and LDH) prior to and routinely during therapy.
    • May cause ↑ uric acid concentrations.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)
Risk for injury (Side Effects)

Implementation

  • high alert: 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.
  • high alert: 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 (see ).
    • May be given subcut, direct IV, intermittent IV, continuous IV, or IT.
  • Intravenous: Subcutaneous: Reconstitute 100-mg vials with 5 mL of bacteriostatic water for injection with benzyl alcohol 0.9% for a concentration of 20 mg/mL. Reconstitute 500-mg vials with 10 mL for a concentration of 50 mg/mL, 1-g vials with 10 mL, and 2-g vials with 20 mL for a concentration of 100 mg/mL. Reconstituted solution is stable for 48 hr. Do not administer a cloudy or hazy solution.
  • Intravenous Administration
  • pH: 7.0–9.0.
  • Diluent: Administer undiluted.Concentration: 100 mg/mL.
  • Rate: Administer each 100 mg over 1–3 min
  • 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.
  • Continuous Infusion: Rate and concentration for IV infusion are ordered individually.
  • Y-Site Compatibility: acyclovir, alemtuzumab, alfentanil, amifostine, amakacin, aminocaproic acid, aminophylline, amphotericin B cholesteryl, amphotericin B lipid complex, amphotericin B liposome, ampicillin, ampicillin/sulbactam, amsacrine, anidulafungin, argatroban, atracurium, azithromycin, aztreonam, bivalirudin, bleomycin, bumetanide, buprenorphine, butorphanol, calcium chloride, calcium gluconate, carboplatin, carmustine, cefazolin, cefepime, cefoperazone, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, chlorpromazine, ciprofloxacin, cisatracurium, cisplatin, cladribine, clindamycin, cyclophosphamide, cyclosporine, daunorubicin hydrochloride, dexamethasone phosphate, dexmedetomidine, dexrazoxane, digoxin, diltiazem, diphenhydramine, dobutamine, docetaxel, dolasetron, dopamine, doxacurium, doxorubicin hydrochloride, doxorubicin liposome, doxycycline, droperidol, enalaprilat, ephedrine, epinephrine, ertapenem, erythromycin, esmolol, etoposide, etoposide phosphate, famotidine, fenolsopam, fentanyl, filgrastim, fluconazole, fludarabine, foscarnet, fosphenytoin, furosemide, gemcitabine, gentamicin, granisetron, haloperidol, heparin, hydrocortisone, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, insulin, irinotecan, isoproterenol, ketorolac, labetalol, leucovorin, levofloxacin, levorphanol, lidocaine, linezolid, lorazepam, magnesium sulfate, mannitol, melphalan, meperidine, meropenem, mesna, methohexital, methotrexate, methylprednisolone, metoclopramide, metoprolol, metronidazole, midazolam, milrinone, mitoxantrone, morphine, nalbuphine, naloxone, nesiritide, nicardipine, nitroglycerin, nitroprusside, norepinephrine, octreotide, ondansetron, oxaliplatin, paclitaxel, palonosetron, pamidronate, pancuronium, pantoprazole, pemetrexed, pentamidine, pentobarbital, phenobarbital, phenylephrine, piperacillin/tazobactam, potassium acetate, potassium chloride, potassium phosphates, procainamide, prochlorperazine, promethazine, propofol, propranolol, quinupristin/dalfopristin, ranitidine, remifentanil, rituximab, rocuronium, sargramostim, sodium acetate, sodium bicarbonate, sodium phosphates, succinylcholine, sufentanil, tacrolimus, teniposide, theophylline, thiopental, thiotepa, ticarcillin/clavulanate, tigecycline, tirofiban, tobramycin, trastuzumab, trimethoprim/sulfamethoxazole, vancomycin, vasopressin, vecuronium, verapamil, vincristine, vinorelbine, voriconazole, zidovudine, zoledronic acid
  • Y-Site Incompatibility: allopurinol, amiodarone, amphotericin B colloidal, daptomycin, diazepam, ganciclovir, phenytoin
  • Intrathecal: Patients receiving liposomal cytarabine should be started on dexamethasone 4 mg twice daily PO or IV for 5 days beginning on the day of liposomal cytarabine injection.
    • Allow vial to warm to room temperature. Gently agitate or invert vial to resuspend particles immediately before withdrawal from vial. No further reconstitution or dilution is required with liposomal cytarabine. Reconstitute conventional cytarabine with preservative-free 0.9% NaCl or autologous spinal fluid. Use immediately to prevent bacterial contamination.
    • Liposomal cytarabine must be used within 4 hr of withdrawal from the vial. Discard unused portions. Inject directly into CSF via intraventricular reservoir or by direct injection into lumbar sac. Do not use in-line filters.
    • Instruct patient to lie flat for 1 hr following IT injection. Monitor for immediate toxic reactions.

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.
  • 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.
  • Intrathecal: 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.
    • Emphasize the importance of taking dexamethasone with lyposomal cytarabine.

Evaluation/Desired Outcomes

  • Improvement of hematopoietic values in leukemias.
  • Decrease in size and spread of the tumor in non-Hodgkin’s lymphomas. Therapy is continued every 2 wk until patient is in complete remission or thrombocyte count or leukocyte count falls below acceptable levels.
  • Treatment of lymphomatous meningitis.

Cytosar

A brand name for CYTARABINE.