cytarabine (Rx)
Generic: Cytarabine
Brand: Ara-C, Cytosar ♣, Cytosar-U
(sye-tare'a-been)
Pharmacological Action
Competes with physiologic substrate of DNA synthesis, thus interfering with cell replication in the S phase of the cell cycle (before mitosis)
Therapeutic outcome: Prevention of rapidly growing malignant cells
Uses
Acute myelocytic leukemia, acute lymphocytic leukemia, chronic myelocytic leukemia, lymphomatous meningitis (IT/intraventricular)
Contraindications
Pregnancy D, hypersensitivity
Precautions: Renal/hepatic disease, breastfeeding, children, tumor lysis syndrome, infection, hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia
BLACK BOX WARNING: Bone marrow suppression
Dosage & Routes
Acute myelogenous leukemia (AML)
Adult: cont IV infusion 100 mg/m2/day 3 7 days q2 wk as a single agent or 2-3 divided doses 3 5-10 days until remission used in combination; maintenance 70-200 mg/m2/day 3 2-5 days qmo; SUBCUT maintenance 100 mg/m2/day 3 5 days q28 days Meningeal leukemia Adult and child: Intrathecal 5-70 mg/m2 variable daily 3 4 days to q2-7 day Carcinomatous meningitis (liposomal)
Adult: Intrathecal 50 mg over 1-5 min q14 days, during induction and consolidation wk 1, 3, 5, 7, 9, give another 50 mg wk 13; maintenance 50 mg q28 days on wk 17, 21, 25, 29 use with dexamethasone 4 mg PO/IV 3 5 days on each day of cytarabine Renal dose Adult CCr ≤60 ml/min, serum creatinine 1.5-1.9 mg/dl or increase of 0.5-1.2 mg/dl from baseline: during treatment reduce to 1 g/m2/dose; serum creatinine ≥2 mg/dl or change from baseline serum creatinine was 1.2 mg/dl reduce to 100 mg/m2/day
Available forms: Powder for inj 100, 500 mg, 1, 2 g; sus rel (Depo Cyt) liposomal for intrathecal use 10 mg/ml
Implementation - Avoid contact with skin; very irritating; wash completely to remove - Give fluids IV or PO before chemotherapy to hydrate patient - Give antiemetic 30-60 min before giving product to prevent vomiting, and prn; antibiotics for prophylaxis of infection - Increase fluids to 3 L/day - Give top or syst analgesics for pain - Give in am so product can be eliminated before bedtime - Use cytotoxic handling precautions IM/SUBCUT route - Reconstitute 100 mg/5 ml or 500 mg/10 ml with bacteriostatic water for inj with benzyl alcohol 0.9%; do not use sol with precipitate; stable for 48 hr Intrathecal route -
Liposomal: withdraw product immediately before use; use within 4 hr, do not save unused portions or use in-line filter; give directly into CSF by intraventricular reservoir or by direct inj into lumbar site - Give slowly over 1-5 min; follow with lumbar puncture; instruct patient to lie flat; give dexamethasone 4 mg bid PO or IV 3 5 days beginning on day of liposomal inj Direct IV route - Dilute 100 mg/5 ml of sterile water for inj, give over 1-3 min through a free-flowing IV Intermittent IV infusion route - May be further diluted in 50-100 ml NS or D5 W and give over 30 min-24 hr, depending on dose Continuous IV infusion route - May be given as continuous IV infusion
Adverse Effects
CNS: Neuritis, dizziness, headache, cerebellar syndrome, personality changes, ataxia, mechanical dysphasia, coma; chemical arachnoiditis (IT)
CV: Chest pain, cardiopathy
EENT: Sore throat, conjunctivitis
GI: Nausea, vomiting, anorexia, diarrhea, stomatitis, hepatotoxicity, abdominal pain, hematemesis, GI hemorrhage
GU: Urinary retention, renal failure, hyperuricemia
HEMA: Thrombophlebitis, bleeding, thrombocytopenia, leukopenia, myelosuppression, anemia
INTEG: Rash, fever, freckling, cellulitis
META: Hyperuricemia
MISC: Cytarabine syndrome—fever, myalgia, bone pain, chest pain, rash, conjunctivitis, malaise (6-12 hr after administration)
RESP: Pneumonia, dyspnea, pulmonary edema (high doses)
SYST: Anaphylaxis, tumor lysis syndrome
Pharmacokinetics
Absorption: Complete
Distribution: Widely distributed; crosses blood-brain barrier, placenta
Metabolism: Liver, extensively
Excretion: Kidneys
Half-life: Distribution 10 min; elimination 1-3 hr; IT 100-236 hr
Pharmacodynamics
Unknown
Interactions
Individual drugs Digoxin oral: decreased digoxin effects Filgrastim, G-CSF, GM-CSF, sargramostim: do not use within 24 hr Flucytosine, methotrexate: increased toxicity, immunosuppression
Gentamicin: decreased effects
Radiation: increased toxicity, bone marrow suppression
Drug classifications Anticoagulants, NSAIDs, platelet inhibitors, salicylates, thrombolytics: increased bleeding risk Immunosuppressants, antineoplastics: increased toxicity, bone marrow suppression Live virus vaccines: do not use together
Nursing Considerations
Assessment - Assess buccal cavity q8 hr for dryness, sores or ulceration, white patches, pain, bleeding, dysphagia; obtain prescription for viscous lidocaine (Xylocaine) - Assess symptoms indicating anaphylaxis: rash, pruritus, urticaria, purpuric skin lesions, itching, flushing; resuscitation equipment should be nearby - Assess for chemical arachnoiditis (IT): headache, nausea, vomiting, fever; neck rigidity/pain, meningism, CSF pleocytosis; may be decreased by dexamethasone - Assess tachypnea, dyspnea, edema, fatigue; identify dyspnea, crackles, unproductive cough, chest pain, tachypnea; pulmonary edema may be fatal (rare) - Assess for cytarabine syndrome 6-12 hr after infusion: fever, myalgia, bone pain, chest pain, rash, conjunctivitis, malaise; corticosteroid may be ordered - Bone marrow suppression: Monitor CBC, differential, platelet count weekly; withhold product if WBC count is <1000/mm3 or platelet count is <50,000/mm3 - Assess for increased uric acid levels, swelling, joint pain primarily in extremities; patient should be well hydrated to prevent urate deposits - Monitor renal function studies: BUN, creatinine, serum uric acid, urine CCr before and during therapy; • I&O ratio; report fall in urine output to <30 ml/hr - Monitor temp q4 hr (may indicate beginning of infection) -
Hepatotoxicity: Monitor liver function tests before and during therapy (bilirubin, AST, ALT, LDH) as needed or monthly; note yellowing of skin or sclera, dark urine, clay-colored stools, pruritus, abdominal pain, fever, diarrhea; an antispasmodic may be used for GI symptoms - Assess for bleeding: hematuria, stool guaiac, bruising or petechiae, mucosa or orifices q8 hr; identify inflammation of mucosa, breaks in skin
Patient/family education - Advise patient that contraceptive measures are recommended during and 4 mo after therapy - Teach patient to avoid use of products containing aspirin or ibuprofen, NSAIDs, razors, commercial mouthwash, since bleeding may occur; to report symptoms of bleeding (hematuria, tarry stools) - Advise that fever, headache, nausea, vomiting are likely to occur but to continue using dexamethasone with IT administration - Provide liquid diet: carbonated beverages; gelatin may be added if patient is not nauseated or vomiting - Provide rinsing of mouth tid-qid with water, club soda; brushing of teeth bid-qid with soft brush or cotton-tipped applicators for stomatitis; use unwaxed dental floss - Advise patient to report signs of anemia (fatigue, headache, irritability, faintness, shortness of breath) - Advise patient to avoid foods with citric acid, hot flavor, or rough texture if stomatitis is present, to use sponge brush and rinse with water after each meal; to report stomatitis: any bleeding, white spots, ulcerations in mouth; tell patient to examine mouth daily, report any symptoms - Instruct patient to report any changes in breathing or coughing even several months after treatment; to avoid crowds and persons with respiratory tract or other infections; neurotoxicity - Caution patient not to have any vaccinations without the advice of the prescriber; serious reactions can occur - Advise patient to take 3 L/day fluids to prevent renal damage
Evaluation
Positive therapeutic outcome: Prevention of rapid division of malignant cells
Reference
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