Names and pronunciation
(sye-kloe-foss′fa-mide) Procytox
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Drug reference
(sye-kloe-foss′fa-mide) Procytox
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Func. class.: Antineoplastic alkylating agent
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Chem. class.: Nitrogen mustard
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Do not confuse: cyclophosphamide/cycloSPORINE
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ACTION: Alkylates DNA; is responsi- ble for cross-linking DNA strands; activity is not cell-cycle–phase specific
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USES: Hodgkin’s disease, lymphomas, leukemia; cancer of female reproductive tract, breast, multiple myeloma; neuro- blastoma; retinoblastoma; Ewing’s sar- coma; nephrotic syndrome
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CONTRAINDICATIONS: Preg- nancy, hypersensitivity, prostatic hyper- trophy, bladder neck obstruction Precautions: Radiation therapy, cardiac disease, anemia, dysrhythmias, child, den- tal disease/work, dialysis, geriatric patients, heart failure, hematuria, infections, leukopenia QT prolongation, secondary malignancy surgery, tumor lysis syndrome, vaccinations, breastfeeding, severely depressed bone marrow function
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SIDE EFFECTS CV: Cardiotoxicity (high doses), myo- cardial fibrosis, hypotension ENDO: SIADH, gonadal suppression GI: Nausea, vomiting, weight loss, anorexia GU: Hemorrhagic cystitis, hematuria HEMA: Thrombocytopenia, leukopenia, myelosuppression INTEG: Alopecia META: Hyperuricemia MISC: Secondary neoplasms RESP: Pulmonary fibrosis, interstitial pneumonia
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INTERACTIONS Increase: neuromuscular blockade— succinylcholine Increase: action of warfarin Increase: bone marrow depression— other antineoplastics, radiation, allopuri- nol, thiazides Decrease: digoxin levels—digoxin Decrease: cyclophosphamide effect Decrease: antibody response—live virus vaccines Drug/Herb Increase: toxicity—St. John’s wort Drug/Lab Test Increase: uric acid False positive: Pap smear False negative: PPD, mumps, Candida, Trichophyton, Pap smear
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DOSAGE AND ROUTES Acute lymphocytic leukemia (ALL) • Adult/adolescent/child: IV Total doses of IV 300-1500 mg/m2 have been incorporated into induction, intensifica- tion, consolidation regimens, possibly using vinCRIStine, predniSONE, or oth- ers; PO 1-5 mg/kg/day depending on response Neuroblastoma • Adult/child: IV For induction, 40-50 mg/kg in divided doses over 2-5 days or 10-15 mg/kg q7-10days, 3-5 mg/kg 2×/ wk or 1-5 mg/kg daily • Child and infant: PO 150 mg/m2/day, days 1-7 with DOXOrubicin (IV 35 mg/ m2 on day 8) q21days × 5 cycles • Child: IV 70 mg/kg/day with hydration on days 1, 2 with DOXOrubicin and vin- CRIStine q21days for courses 1, 2, 4, 6 alternating with CISplatin and etoposide q21days for courses 3, 5, 7 Breast cancer • Adult: PO 100-200 mg/m2/day or 2 mg/kg/day × 4-14 days; IV 500-1000 mg/m2 on day 1 in combination with fluorouracil and methotrexate or DOXO- rubicin or DOXOrubicin alone, also cy- clophosphamide 600 mg/m2; may be given dose-dense on day 1 of q14days with DOXOrubicin (60 mg/m2) with growth-factor support Operable node-positive breast cancer IV (TAC regimen) • Adult: IV 500 mg/m2 with DOXOrubi- cin (50 mg/m2 IV), then DOCEtaxel (75 mg/m2) IV given 1 hr later q3wk × 6 cycles Nephrotic syndrome • Child: PO 2 mg/kg daily × 60-90 days, cumulative dose 168 mg/kg
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Available forms: Powder for injection 200, 500 mg, 1, 2 g/vials; capsules 25, 50 mg
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Administer: • Use cytotoxic handling procedures • In AM so product can be eliminated before bedtime • Fluids IV or PO prior to chemotherapy to hydrate patient • Antacid prior to oral agent; give after evening meal, before bedtime • Antiemetic 30-60 min before product and prn • Allopurinol or sodium bicarbonate to maintain uric acid levels, alkalinization of urine PO route • Take on empty stomach; do not crush, break, chew capsules; wash hands im- mediately if in contact with capsules • May be taken as a single dose or di- vided doses • Take in AM or afternoon, avoid evening • Store in tight container at room tem- perature Direct IV route • Reconstitute with NS only 100 mg/5 mL, swirl, inject slowly Intermittent IV INFUSION route • Use cytotoxic handling procedures • IV after diluting 100 mg/5 mL, 0.9% NaCl of sterile water or bacteriostatic water; shake; let stand until clear; may be further diluted in ≤250 mL D5/NS, 0.45% NaCl; give 100 mg or less/min (2 mg/mL) • Use 21, 23, 25G needle; check site for irritation, phlebitis Y-site compatibilities: Acyclovir, alfent- anil, allopurinol, amifostine, amikacin, aminocaproic acid, aminophylline, amio- darone, amphotericin B lipid complex, amphotericin B liposome, ampicillin, ampicillin-sulbactam, anidulafungin, aten- olol, atracurium, azlocillin, aztreonam, bivalirudin, bleomycin, bumetanide, buprenorphine, butorphanol, calcium chloride/gluconate, CARBOplatin, caspo- fungin, cefamandole, ceFAZolin, cefepime, cefoperazone, cefotaxime, cefoTEtan, cefOXitin, cefTAZidime, ceftizoxime, cefTRIAXone, cefuroxime, chloramphenicol, chlorproMAZINE, cimetidine, ciprofloxacin, cisatracurium, CISplatin, cladribine, clindamycin, codeine, cycloSPORINE, cytarabine, DACTINomycin, DAPTOmycin, DAUNOru- bicin, dexamethasone, dexmedetomidine, dexrazoxane, digoxin, diltiaZEM, diphen- hydrAMINE, DOBUTamine, DOCEtaxel, dolasetron, DOPamine, doripenem, doxa- C curium, DOXOrubicin, DOXOrubicin lipo- somal, doxycycline, droperidol, enala- prilat, ePHEDrine, EPINEPHrine, epiRUBicin, ertapenem, erythromycin, esmolol, etoposide, famotidine, fenoldo- pam, fentaNYL, filgrastim, fluconazole, fludarabine, fluorouracil, foscarnet, fos- phenytoin, furosemide, gallium, ganciclo- vir, gatifloxacin, gemcitabine, gentamicin, granisetron, haloperidol, heparin, hydro- cortisone, HYDROmorphone, hydrOXY- zine, IDArubicin, imipenem- cilastatin, inamrinone, insulin (regular), irinotecan, isoproterenol, kanamycin, ketorolac, labetalol, leucovorin, levoFLOX- acin, levorphanol, lidocaine, linezolid, LORazepam, magnesium sulfate, mannitol, melphalan, meperidine, meropenem, mesna, methohexital, methotrexate, meth- ylPREDNISolone, metoclopramide, meto- prolol, metroNIDAZOLE, midazolam, mil- rinone, minocycline, mitoMYcin, mitoXANTRONE, mivacurium, morphine, nafcillin, nalbuphine, naloxone, nesiritide, nitroglycerin, nitroprusside, norepineph- rine, octreotide, ondansetron, oxacillin, oxaliplatin, PACLitaxel, palonosetron, pamidronate, pancuronium, pantopra- zole, PEMEtrexed, penicillin G potassium, pentamidine, PENTobarbital, PHEN obarbital, phenylephrine, piperacillin, piperacillin-tazobactam, potassium chloride/phosphates, procainamide, pro- chlorperazine, promethazine, propofol, propranolol, quinupristin-dalfopristin, raNITIdine, rapacuronium, remifentanil, riTUXimab, rocuronium, sargramostim, sodium acetate/bicarbonate/phosphates, succinylcholine, SUFentanil, sulfamethox- azole-trimethoprim, tacrolimus, tenipo- side, theophylline, thiopental, thiotepa, ticarcillin, ticarcillin-clavulanate, tigecy- cline, tirofiban, TNA, tobramycin, topote- can, TPN, trastuzumab, vancomycin, vaso- pressin, vecuronium, verapamil, vinBLAStine, vinCRIStine, vinorelbine, voriconazole, zidovudine, zoledronic acid
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Assess: • Hemorrhagic cystitis; renal stud- ies: BUN, serum uric acid, urine CCr prior to, during therapy; I&O ratio; report fall in urine output <30 mL/hr; provide increased fluid intake to 3 L/day (adults) • Bone marrow depression: CBC, dif- ferential, platelet count baseline, weekly; withhold product if WBC is <2500 or plate- let count is <75,000; notify prescriber. As- sess for hematuria, guaiac, bruising or pe- techiae, mucosa or orifices q8hr • Pulmonary fibrosis/interstitial pneu- monia: pulmonary function tests, chest x- ray films prior to, during therapy; chest film should be obtained q2wk during treat- ment; monitor for dyspnea, rales/crackles, edema • Hepatotoxicity: hepatic studies prior to, during therapy (bilirubin, AST, ALT, LDH), as needed; jaundice of skin, sclera; dark urine, clay-colored stools; itchy skin; abdominal pain; fever; diarrhea • Unproductive cough, chest pain, tachypnea • Buccal cavity q8hr for dryness, sores or ulceration, white patches, oral pain, bleeding, dysphagia; obtain prescription for viscous lidocaine (Xylocaine); provide rinsing of mouth tid-qid with water, club soda; brushing of teeth bid-tid with soft brush or cotton-tipped applicators for sto- matitis; use unwaxed dental floss • Increase fluid intake to 2-3 L/day to prevent urate deposits, calculi forma- tion, reduce incidence of hemorrhagic cystitis • Warm compresses at injection site for inflammation • Beers: avoid in older adults; delir- ium, dementia may occur; avoid in men due to decrease in urine flow, retention
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Evaluate: • Therapeutic response: decreased tu- mor size, spread of malignancy; ne- phrotic syndrome
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To take adequate fluids (3 L/day, adults) to eliminate product • That amenorrhea can occur and may last up to 1 yr after therapy but is revers- ible after stopping treatment • To report any changes in breathing or coughing • To avoid foods with citric acid, hot temperature, or rough texture; that skin, fingernails may become darker • To report signs of infection: increased temperature, sore throat, flulike symptoms • To report signs of anemia: fatigue, headache, faintness, SOB, irritability • To report bleeding (bruising, hematu- ria, petechiae); to avoid the use of razors, commercial mouthwash • To avoid the use of aspirin products, ibuprofen • To avoid vaccinations during therapy • About proper handling and disposal of chemotherapy drugs • Pregnancy/breastfeeding: to use re- liable contraception during treatment and for 1 yr after treatment (women); men should use condoms during and for 4 mo following treatment; not to breastfeed
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PHARMACOKINETICS Metabolized by liver, excreted in urine, half-life 4-6½ hr, 50% bound to plasma proteins
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• Adult/adolescent/child: IV Total doses of IV 300-1500 mg/m2 have been incorporated into induction, intensifica- tion, consolidation regimens, possibly using vinCRIStine, predniSONE, or oth- ers; PO 1-5 mg/kg/day depending on response Neuroblastoma
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• Adult/child: IV For induction, 40-50 mg/kg in divided doses over 2-5 days or 10-15 mg/kg q7-10days, 3-5 mg/kg 2×/ wk or 1-5 mg/kg daily
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• Adult: PO 100-200 mg/m2/day or 2 mg/kg/day × 4-14 days; IV 500-1000 mg/m2 on day 1 in combination with fluorouracil and methotrexate or DOXO- rubicin or DOXOrubicin alone, also cy- clophosphamide 600 mg/m2; may be given dose-dense on day 1 of q14days with DOXOrubicin (60 mg/m2) with growth-factor support Operable node-positive breast cancer IV (TAC regimen)
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• Adult: IV 500 mg/m2 with DOXOrubi- cin (50 mg/m2 IV), then DOCEtaxel (75 mg/m2) IV given 1 hr later q3wk × 6 cycles Nephrotic syndrome
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