Names and pronunciation
(i-foss′fa-mide) Ifex
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Drug reference
(i-foss′fa-mide) Ifex
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Func. class.: Antineoplastic alkylating agent
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Chem. class.: Nitrogen mustard
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Do not confuse: ifosfamide/cyclophosphamide
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ACTION: Alkylates DNA, inhibits enzymes that allow synthesis of amino acids in proteins; also responsible for cross-linking DNA strands; activity is not cell-cycle–stage specific
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USES: Germ cell testicular cancer in combination
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Unlabeled uses: Soft tissue sarcoma, ALL, Ewing sarcoma, NHL, NSCLC, osteo- genic sarcoma, penile cancer
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CONTRAINDICATIONS: Preg- nancy, hypersensitivity Precautions: Breastfeeding, children, I renal/hepatic/cardiac disease, accidental exposure, infection, varicella, anemia, chronic lung disease, geriatrics, radiation therapy
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Black Box Warning: Coma, hemorrhagic cystitis, bone marrow suppression, neu- rotoxicity, nephrotoxicity, encephalopathy Black Box Warning: Bone marrow sup- pression: CBC, differential, platelet count weekly; withhold product if WBC <2000/ mm3 or platelet count <50,000/mm3; no- tify prescriber; severe myelosuppression may occur, nadir of leukopenia, thrombo- cytopenia 7-14 days, recovery 21 days • Monitor temperature, flu like symp- toms (may indicate beginning infection) • B/P, pulse, respirations, baseline and periodically during treatment • Blood dyscrasias (anemia, granulocy- topenia); bruising, fatigue, bleeding, poor healing • Allergic reactions: dermatitis, exfo- liative dermatitis, pruritus, urticaria Black Box Warning: Hemorrhagic cys- titis: I&O ratio; monitor for hematuria; hemorrhagic cystitis can occur; increase fluids to 3 L/day; urinalysis before each dose, not to give at night, give with mes- na to prevent this condition Black Box Warning: Neurotoxicity: hal- lucinations, confusion, disorientation, coma; product should be discontinued, usually resolves in 3-4 days • Bleeding: hematuria, guaiac, bruising or petechiae, mucosa or orifices; avoid IM injections • Pregnancy/breastfeeding: do not use in pregnancy/breastfeeding
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SIDE EFFECTS CNS: Facial paresthesia, fever, malaise, somnolence, confusion, depression, hal- lucinations, dizziness, disorientation, seizures, coma, cranial nerve dysfunc- tion, encephalopathy GI: Nausea, vomiting, anorexia, hepato toxicity, stomatitis, dyslipidemia, hyper- glycemia, constipation, diarrhea GU: Hematuria, nephrotoxicity, hemor- rhagic cystitis, dysuria, urinary frequency HEMA: Thrombocytopenia, leukopenia, anemia, retrograde ejaculation INTEG: Dermatitis, alopecia, pain at inj site, hyperpigmentation META: Metabolic acidosis, infection RESP: Pulmonary toxicity
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INTERACTIONS Do not use within 24 hr of hematopoietic progenitor cells Increase: myelosuppression—other anti- neoplastics, radiation Increase: toxicity—CYP3A4, inducers, (barbiturates, carbamazepine, phenytoin, rifampin) Increase: bleeding risk—NSAIDs, anti- coagulants, salicylates, thrombolytics Decrease: antibody response—live virus vaccines Decrease: effect of ifosfamide—CYP3A4 inhibitors Drug/Herb Increase: toxicity—St. John’s Wort Drug/Lab Increase: LFTs, BUN, creatinine Decrease: Platelets, WBC Drug/Food Increase: levels avoid with grapefruit juice
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DOSAGE AND ROUTES Germ cell testicular cancer • Give with mesna for uroprotective treatment • Adult: IV 1.2-2 g/m2/day × 5 days, repeat course q3wk, given with mesna, in combination with 1-2 other antineoplas- tic agents Sarcoma of soft tissue (orphan drug designation) (unlabeled) • Adult: IV INFUSION MAID regimen: DOXOrubicin 60 mg/m2 and dacarbazine 1000 mg/m2, mixed or administered separately via CONT IV INFUSION over 4 days, ifosfamide 6000 mg/m2 and mesna 10,000 mg/m2 mixed or infused separately over 3 days (ifosfamide) and 4 days (mesna); repeat q21days if toler- ated; OR MAID regimen: DOXOrubicin 60 mg/m2 and dacarbazine 900 mg/m2, mixed and administered through central venous access via CONT IV INFU- SION over 3 days, ifosfamide 7500 mg/ m2 and mesna 10,000 mg/m2 mixed or infused separately through a peripheral line via a CONT IV INFUSION over 3 days (ifosfamide) and 4 days (mesna); repeat q21days if tolerated Renal dose • Adult: IV CCr 31-60 mL/min, give 75% of dose; CCr 10-30 mL/min, give 50% of dose; CCr <10 mL/min, do not give
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Available forms: Inj 1-, 3-g vials
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Administer: • Antiemetic 30-60 min before product to prevent vomiting • Give mesna IV concurrently and 4 and 8 hr after each dose being 20% of ifosfamide dose • Visually inspect parenteral products for particulate matter and discoloration before use • Store powder at room temperature Intermittant/continuous IV infusion route • Give as an intermittent infusion or continuous infusion • Well hydrate with ≥2 L/day of oral or IV fluids to prevent bladder toxicity • Close hematologic monitoring is rec- ommended; WBC count, platelet count, and hemoglobin should be obtained be- fore each use and periodically thereafter • A urinalysis should be performed be- fore each dose to monitor for hematuria Reconstitution and further dilution: • Reconstitute 1 or 3 g with 20 or 60 mL, respectively, of sterile water for injection or bacteriostatic water for injection containing parabens or benzyl alcohol to give IV solutions containing 50 mg/mL • Solutions may be diluted further to achieve concentrations of 0.6-20 mg/mL in the following solutions: D5W, NS, LR, or sterile water for injection • Infuse slowly over at least 30 min • Diluted and reconstituted solutions must be refrigerated and used within 24 hr Y-site compatibilities: Acyclovir, alatro- floxacin, alemtuzumab, alfentanil, allopu- rinol, amifostine, amikacin, aminocaproic acid, aminophylline, amiodarone ampho- tericin B cholesteryl (amphotec), ampho- tericin B conventional colloidal, ampho- tericin B lipid complex (abelcet), amphotericin B liposome (ambisome), ampicillin, ampicillin-sulbactam, anidulafungin, argatroban, arsenic triox- ide, atenolol, atracurium, azithromycin, aztreonam, bivalirudin, bleomycin, bumetanide, buprenorphine, butorpha- nol, calcium chloride/gluconate, CARBO- platin, caspofungin, ceFAZolin, cefopera- zone, cefotaxime, cefoTEtan, cefOXitin, cefTAZidime, cefTAZidime (L-arginine), ceftizoxime, cefTRIAXone, cefuroxime, chlorproMAZINE, cimetidine, ciprofloxa- cin, cisatracurium, CISplatin, clindamy- cin, codeine, cycloSPORINE, cytarabine, DACTINomycin, DAPTOmycin, DAUNOru- bicin liposome, dexamethasone phos- phate, dexmedetomidine, dexrazoxane, digoxin, diltiaZEM, diphenhydrAMINE, DOBUTamine, DOCEtaxel, dolasetron, DOPamine, doripenem, doxacurium, DOXOrubicin, DOXOrubicin liposomal, doxycycline, droperidol, enalaprilat, ePHEDrine, EPINEPHrine, epiRUBicin, ertapenem, erythromycin, esmolol, etopo- side, etoposide phosphate, famotidine, fenoldopam, fentaNYL, filgrastim, flucon- azole, fludarabine, fluorouracil, foscarnet, fosphenytoin, furosemide, gallium nitrate, ganciclovir, gatifloxacin, gemcitabine, gemtuzumab, gentamicin, granisetron, haloperidol, heparin, hydrocortisone phosphate/succinate, HYDROmorphone, hydrOXYzine, IDArubicin, imipenem- cilastatin, inamrinone, insulin (regular), isoproterenol, ketorolac, labetalol, lanso- prazole, lepirudin, leucovorin, levoFLOXa- cin, levorphanol, lidocaine, linezolid, LORazepam, magnesium sulfate, manni- tol, melphalan, meperidine, meropenem, mesna, methohexital, methylPREDNISo- lone, metoclopramide, metoprolol, met- roNIDAZOLE, midazolam, milrinone, minocycline, mitoMYcin, mitoXANTRONE, mivacurium, morphine, moxifloxacin, nalbuphine, naloxone, nesiritide, niCAR- dipine, nitroglycerin, nitroprusside, nor- epinephrine, octreotide, ofloxacin, ondansetron, oxaliplatin, PACLitaxel (sol- vent/surfactant), palonosetron, pamidro- nate, pancuronium, PEMEtrexed, pent- amidine, PENTobarbital, PHENobarbital, phenylephrine, piperacillin, piperacillin- tazobactam, potassium acetate/chloride, procainamide, prochlorperazine, pro methazine, propofol, propranolol, quinupristin-dalfopristin, raNITIdine, rapacuronium, remifentanil, riTUXimab, rocuronium, sargramostim, sodium acetate/bicarbonate/phosphates, succinyl- choline, SUFentanil, sulfamethoxazole-tri- methoprim, tacrolimus, teniposide, the- ophylline, thiopental, thiotepa, ticarcillin, ticarcillin-clavulanate, tigecycline, tirofi- ban, TNA (3-in-1), tobramycin, topotecan, TPN (2-in-1), trastuzumab, vancomycin, vasopressin, vecuronium, verapamil, vin- BLAStine, vinCRIStine, vinorelbine, vori- conazole, zidovudine, zoledronic acid
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Assess: • Hepatic studies before, during ther- apy (bilirubin, AST, ALT, LDH) monthly or as needed; jaundice of skin and sclera, dark urine, clay-colored stools, itchy skin, abdominal pain, fever, diarrhea I
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Evaluate: • Therapeutic response: decrease in size and spread of tumor
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To notify prescriber of sore throat, swollen lymph nodes, malaise, fever; other infections may occur, to discuss encephalopathy, neurotoxicity • Not to have live virus vaccinations dur- ing or for 3 mo-1 yr after treatment • That hair may be lost during treatment; that wig or hairpiece may make the pa- tient feel better; that new hair may be different in color, texture • To report signs of anemia: fatigue, headache, faintness, SOB, irritability • To report bleeding; to avoid use of razors, commercial mouthwash; to avoid use of aspirin products, NSAIDs, ibuprofen because hemorrhage can oc- cur • To avoid crowds, persons with infections • To report confusion, hallucinations, extreme drowsiness, numbness, tingling; to avoid alcohol use for ≥4 mo after treatment • To avoid driving, hazardous activities until reaction is known • To use excessive fluids and urinate of ten to prevent hemorrhagic cystitis; to report pink or red urine • To notify prescriber if pregnancy is planned or suspected; to use contracep tive measures during therapy; not to breastfeed
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PHARMACOKINETICS Metabolized by liver; saturation occurs at high doses; excreted in urine, breast milk; half-life 7-15 hr, depends on dose; onset unknown, peak 1-2 wk, duration 3 wk
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• Adult: IV 1.2-2 g/m2/day × 5 days, repeat course q3wk, given with mesna, in combination with 1-2 other antineoplas- tic agents Sarcoma of soft tissue (orphan drug designation) (unlabeled)
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• Adult: IV INFUSION MAID regimen: DOXOrubicin 60 mg/m2 and dacarbazine 1000 mg/m2, mixed or administered separately via CONT IV INFUSION over 4 days, ifosfamide 6000 mg/m2 and mesna 10,000 mg/m2 mixed or infused separately over 3 days (ifosfamide) and 4 days (mesna); repeat q21days if toler- ated; OR MAID regimen: DOXOrubicin 60 mg/m2 and dacarbazine 900 mg/m2, mixed and administered through central venous access via CONT IV INFU- SION over 3 days, ifosfamide 7500 mg/ m2 and mesna 10,000 mg/m2 mixed or infused separately through a peripheral line via a CONT IV INFUSION over 3 days (ifosfamide) and 4 days (mesna); repeat q21days if tolerated Renal dose
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• Adult: IV CCr 31-60 mL/min, give 75% of dose; CCr 10-30 mL/min, give 50% of dose; CCr <10 mL/min, do not give
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