Names and pronunciation
(sye-tare′a-been) Cytosur
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Drug reference
(sye-tare′a-been) Cytosur
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Func. class.: Antineoplastic, antimetabolite
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Chem. class.: Pyrimidine nucleoside analog
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Do not confuse: Cytosar/Cytoxan/Cytovene
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ACTION: Competes with physiologic substrate of DNA synthesis, thus interfer- ing with cell replication in the S phase of the cell cycle (before mitosis)
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USES: Acute myelocytic leukemia, acute nonlymphocytic leukemia, chronic myelocytic leukemia; lymphomatous meningitis (intrathecal/intraventricular) Unlabeled uses: Hodgkin’s/non- Hodgkin’s lymphoma, malignant men- ingitis, mantle cell lymphoma
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CONTRAINDICATIONS: Preg- nancy, hypersensitivity Precautions: Breastfeeding, children, renal/hepatic disease, tumor lysis syn- drome, infection, hyperkalemia, hyperphos- phatemia, hyperuricemia, hypocalcemia
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Black Box Warning: Bone marrow sup- pression, arachnoiditis, abdominal pain, nausea/vomiting of chemotherapy, diar- rhea, hepatotoxicity; requires a special- ized care setting and experienced clini- cian, oral ulceration Black Box Warning: Bone marrow suppression: CBC (RBC, Hct, HB), dif- ferential, platelet count weekly; with- hold product if WBC is <1000/mm3, platelet count is <50,000/mm3, or RBC, Hct, HB are low; notify prescriber of these results; assess for bleeding: he- maturia, heme-positive stools, bruising or petechiae, mucosa, or orifices q8hr • Renal studies: BUN, serum uric acid, urine CCr, electrolytes prior to and dur- ing therapy • I&O ratio; report fall in urine output to <30 mL/hr • Monitor temperature; fever may indi- cate beginning infection; no rectal tem- peratures Black Box Warning: Hepatotoxicity: hepatic studies prior to and during therapy: bilirubin, ALT, AST, alkaline phos- phatase, as needed or monthly; check for jaundice of skin, sclera; dark urine; clay- colored stools; pruritus; abdominal pain; fever; diarrhea • Serum uric acid during therapy • For anaphylaxis: rash, pruritus, facial swelling, dyspnea; resuscitation equip- ment should be nearby Black Box Warning: Chemical arach- noiditis (IT): headache, nausea, vomit- ing, fever; neck rigidity/pain, meningism, CSF pleocytosis; may be decreased by dexamethasone • Cytarabine syndrome 6-12 hr after infusion: fever, myalgia, bone pain, chest pain, rash, conjunctivitis, malaise; corti- costeroids may be ordered • Dyspnea, crackles, unproductive cough, chest pain, tachypnea, fatigue, in- creased pulse, pallor, lethargy; personal- ity changes, with high doses; pulmonary edema may be fatal (rare) • Buccal cavity q8hr for dryness, sores or ulceration, white patches, oral pain, bleeding, dysphagia • Local irritation, pain, burning, discol- oration at injection site • GI symptoms: frequency of stools, cramping; antispasmodic may be used • Increased fluid intake to 2-3 L/day to prevent urate deposits and calculi forma- tion unless contraindicated • Rinsing of mouth tid-qid with water, club soda; brushing of teeth bid-tid with soft brush or cotton-tipped appli- cators for stomatitis; use unwaxed den- tal floss
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SIDE EFFECTS CNS: Dizziness, headache, confusion, drowsiness, chemical arachnoiditis (IT) CV: Edema EENT: Conjunctivitis, visual changes GI: Nausea, vomiting, anorexia, diar- rhea, stomatitis, hepatotoxicity, abdomi- nal pain, GI ulceration (high dose) GU: Urinary retention, renal dysfunction HEMA: Thrombophlebitis, bleeding, thrombocytopenia, leukopenia, myelosup- pression, anemia INTEG: Rash META: Hyperuricemia RESP: Dyspnea, pulmonary edema (high doses) SYST: Anaphylaxis, tumor lysis syndrome Cytarabine syndrome: Fever, myalgia, bone pain, chest pain, rash, conjunctivitis, malaise (6-12 hr after administration)
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INTERACTIONS • Do not use with live virus vaccines • Do not use within 24 hr of chemother- apy—sargramostim, GM-CSF, filgrastim, G-CSF Increase: toxicity—immunosuppressants, methotrexate, flucytosine, radiation, or other antineoplastics Increase: bleeding risk—anticoagulants, platelet inhibitors, salicylates, thrombo- lytics, NSAIDs Decrease: effects of oral digoxin, gentamicin
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DOSAGE AND ROUTES Regimens will vary Acute myelogenous leukemia (AML) • Adult: CONTINUOUS IV INFUSION 100 mg/m2/day × 7 days q2wk as single agent or 2-6 mg/kg/day (100-200 mg/ m2/day) as a single dose or 2-3 divided doses for 5-10 days until remission, used in combination; maintenance 70-200 mg/m2/day for 2-5 days monthly; SUB- CUT/IM maintenance 100 mg/m2/day × 5 days q28days Meningeal leukemia • Adult/child: INTRATHECAL 5-75 mg/ m2, frequency varies Acute promyelocytic leukemia (un- labeled) Adult: CONTINUOUS IV 200 mg/m2 by continuous infusion × 7 days starting on day 3 of therapy with daunorubicin and tretinoin Renal dose • Adult: IV CCr ≤60 mL/min, serum creatinine 1.5-1.9 mg/dL or increase of 0.5-1.2 mg/dL from baseline: 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
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Available forms: Solution for injection 20 mg/mL, 100 mg/mL
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Administer: • Antiemetic 30-60 min prior to product and prn • Allopurinol to maintain uric acid lev- els and alkalinization of the urine IV route • Use cytotoxic handling precautions Direct IV route • Give undiluted, give by direct IV over 1-3 min through free-flowing tubing (IV) Intermittent IV INFUSION route • Dilute in 50-100 mL NS or D5W, given over 30 min to 24 hr, depending on dose Continuous IV INFUSION route • May also be given by continuous infusion Y-site compatibilities: Acyclovir, alfentanil, amifostine, amikacin, aminocaproic acid, aminophylline, amphotericin B lipid com- plex, amphotericin B liposome, ampicillin, ampicillin-sulbactam, amsacrine, anidulafun- gin, atenolol, atracurium, azithromycin, aztreonam, bivalirudin, bleomycin, bumetanide, buprenorphine, butorphanol, calcium chloride/gluconate, CARBOplatin, ceFAZolin, cefepime, cefotaxime, cefoTEtan, cefOXitin, cefTAZidime, ceftizoxime, cefTRI- AXone, cefuroxime, chlorproMAZINE, cimeti- dine, ciprofloxacin, cisatracurium, CISplatin, cladribine, clindamycin, codeine, cyclophos- phamide, cycloSPORINE, DAUNOrubicin, dexamethasone, dexmedetomidine, dexra- zoxane, digoxin, diltiaZEM, diphenhydr- AMINE, DOBUTamine, DOCEtaxel, dolase- tron, DOPamine, doxacurium, DOXOrubicin, DOXOrubicin liposomal, doxycycline, dro- peridol, enalaprilat, ePHEDrine, EPINEPH- rine, ertapenem, erythromycin, esmolol, eto- poside, famotidine, fenoldopam, fentaNYL, filgrastim, fluconazole, fludarabine, foscar- net, fosphenytoin, furosemide, gatifloxacin, gemcitabine, gemtuzumab, gentamicin, granisetron, haloperidol, heparin, hydrocor- tisone, HYDROmorphone, hydrOXYzine, IDA- rubicin, ifosfamide, imipenem-cilastatin, inamrinone, insulin (regular), irinotecan, isoproterenol, ketorolac, labetalol, leucovo- rin, levoFLOXacin, levorphanol, lidocaine, linezolid, LORazepam, magnesium sulfate, mannitol, melphalan, meperidine, meropenem, mesna, methohexital, metho- trexate, methylPREDNISolone, metoclo- pramide, metoprolol, metroNIDAZOLE, mid- azolam, milrinone, minocycline, mitoXANTRONE, mivacurium, morphine, C nalbuphine, naloxone, nesiritide, niCARdip- ine, nitroglycerin, nitroprusside, norepineph- rine, octreotide, ofloxacin, ondansetron, oxaliplatin, PACLitaxel, palonosetron, pami- dronate, pancuronium, pantoprazole, PEME trexed, pentamidine, PENTobarbital, PHENo- barbital, phenylephrine, piperacillin, piperacillin-tazobactam, potassium chloride/ phosphates, procainamide, prochlorpera- zine, promethazine, propofol, propranolol, quinupristin-dalfopristin, raNITIdine, rapa- curonium, remifentanil, riTUXimab, rocuronium, sargramostim, sodium acetate/ bicarbonate/phosphates, succinylcholine, SUFentanil, sulfamethoxazole-trimethoprim, tacrolimus, teniposide, theophylline, thiopen- tal, thiotepa, ticarcillin, ticarcillin-clavulanate, tigecycline, tirofiban, TNA, tobramycin, trastu- zumab, trimethobenzamide, vancomycin, vasopressin, vecuronium, verapamil, vinCRIS- tine, vinorelbine, voriconazole, zidovudine, zoledronic acid
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Assess:
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Evaluate: • Therapeutic response: improvement of hematologic parameters, decrease in size, spread of tumor
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To report any coughing, chest pain, changes in breathing; may indicate be- ginning pneumonia, pulmonary edema • Stomatitis: To avoid foods with citric acid, hot temperature, or rough texture if stomatitis is present; use sponge brush and rinse with water after each meal; to report stomatitis: any bleeding, white spots, ulcerations in mouth; to examine mouth daily, report any symptoms • To report signs of infection: increased temperature, sore throat, flulike symp- toms; to avoid crowds, persons with in- fections • To report signs of anemia: fatigue, headache, faintness, SOB, irritability • To report bleeding; to avoid use of ra- zors, commercial mouthwash, salicylates, NSAIDs, anticoagulants • To use thrombocytopenia precau- tions • To take fluids to 3 L/day to prevent re- nal damage • To avoid receiving vaccines during treatment • That fever, headache, nausea, vomit- ing are likely to occur • Pregnancy/breastfeeding: to use re- C liable contraception during treatment and for 4 mo thereafter; not to breastfeed
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PHARMACOKINETICS INTRATHECAL: Half-life 100-236 hr; metabolized in liver; excreted in urine (primarily inactive metabolite); crosses blood-brain barrier, placenta IV/SUBCUT: Distribution half-life 10 min, elimination half-life 1-3 hr
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• Adult: CONTINUOUS IV INFUSION 100 mg/m2/day × 7 days q2wk as single agent or 2-6 mg/kg/day (100-200 mg/ m2/day) as a single dose or 2-3 divided doses for 5-10 days until remission, used in combination; maintenance 70-200 mg/m2/day for 2-5 days monthly; SUB- CUT/IM maintenance 100 mg/m2/day × 5 days q28days Meningeal leukemia
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• Adult/child: INTRATHECAL 5-75 mg/ m2, frequency varies Acute promyelocytic leukemia (un- labeled) Adult: CONTINUOUS IV 200 mg/m2 by continuous infusion × 7 days starting on day 3 of therapy with daunorubicin and tretinoin Renal dose
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• Adult: IV CCr ≤60 mL/min, serum creatinine 1.5-1.9 mg/dL or increase of 0.5-1.2 mg/dL from baseline: 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
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