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Ifex/Mesnex Kit

Generic Name: Ifosfamide
Class: Antineoplastic Agents
- Alkylating Agents
VA Class: AN100
CAS Number: 3778-73-2

Medically reviewed by Last updated on Jun 30, 2020.


  • Administer only under supervision of qualified clinicians experienced in the use of cancer chemotherapeutic agents.a

  • Hemorrhagic cystitis may occur and may require discontinuance of therapy (See Bladder Toxicity under Cautions).a

  • Severe neurotoxicity (e.g., confusion, coma) may occur and may require discontinuance of therapy (See Nervous System Effects under Cautions).a

  • Severe myelosuppression reported (See Hematologic Effects under Cautions).a


Antineoplastic agent; alkylating agent structurally related to cyclophosphamide.1 2 3 96 103 111 112

Uses for Ifex/Mesnex Kit

Testicular Cancer

Component of various chemotherapeutic regimens as third-line therapy for recurrent or refractory germ cell testicular cancer1 (designated an orphan drug by FDA for this use).5

Soft Tissue Sarcomas

Component of various chemotherapeutic regimens in conjunction with surgery and/or radiation therapy in the treatment of various soft tissue sarcomas2 3 9 33 34 35 36 37 38 39 40 41 42 43 44 45 46 111 (designated an orphan drug by FDA for this use).5


Used alone or in conjunction with other drugs (e.g., etoposide)9 35 36 37 40 41 42 for treatment of localized, metastatic, and recurrent osteosarcoma9 37 40 41 (designated an orphan drug by FDA for this use).5

Bladder Cancer

Used alone9 143 or in combination with other antineoplastic agents144 145 146 147 for treatment of advanced or metastatic bladder cancer.143

Small Cell Lung Cancer

Treatment of small cell lung cancer as part of a combination regimen.2 3 8 9 10 11 12 13 54 132

Cervical Cancer

Component of various combination regimens (e.g., cisplatin and ifosfamide with or without bleomycin) for the treatment of metastatic or recurrent cervical cancer.3 9 20 21 22 23 25 152 153 154 155 156 157 158

Ovarian Cancer

Used alone or in conjunction with other antineoplastic agents for second-line (salvage) therapy in patients with advanced or recurrent ovarian carcinoma.9 26 28 29 135

Non-Hodgkin’s Lymphoma

Treatment of advanced small noncleaved cell lymphoma (Burkitt’s and non-Burkitt’s) in children9 119 as part of a combination regimen.c

Ifex/Mesnex Kit Dosage and Administration


  • Consult specialized references for procedures for proper handling and disposal of antineoplastics.1

  • Adequately hydrate patient prior to and during ifosfamide therapy (e.g., 2 L of oral or IV fluid daily) to minimize urotoxicity.1 2 58 59 141

  • Concomitant therapy with a uroprotective agent (e.g., mesna) recommended during ifosfamide therapy to decrease the incidence of bladder toxicity.1 2 58 59 95 141 160 (See Bladder Toxicity under Cautions.)


For solution and drug compatibility information, see Compatibility under Stability.

Administer by slow IV infusion.1

Handle cautiously (e.g., use protective gloves);1 avoid exposure during handling and preparation of IV solution.1 If skin or mucosal contact occurs, immediately wash skin with soap and water and flush mucosa with water.1

IV Administration


Reconstitute vial containing 1 or 3 g of ifosfamide powder with 20 or 60 mL, respectively, of sterile or bacteriostatic water for injection, to provide a solution containing 50 mg/mL.a

Shake well to ensure complete dissolution.a May be infused directly or further diluted prior to IV infusion.a


May be diluted with 5% dextrose injection, 0.9% sodium chloride injection, lactated Ringer’s injection, or sterile water for injection to a concentration of 0.6–20 mg/mL.a

Rate of Administration

Administer as a slow IV infusion over a period of ≥30 minutes.a


Consult published protocols for the dosage of ifosfamide and other chemotherapeutic agents and the method and sequence of administration.b


Testicular Cancer

1.2 g/m2 daily for 5 consecutive days.a Repeat course of therapy every 3 weeks (or following recovery of patient’s hematologic functions to within acceptable limits), usually for a total of 4 courses.a

Cautions for Ifex/Mesnex Kit


  • Severe bone marrow depression.1

  • Known hypersensitivity to ifosfamide or any ingredient in the formulation.1



Bladder Toxicity

Hemorrhagic cystitis, hematuria, dysuria, and urinary frequency reported frequently.a Hemorrhagic cystitis can be severe and may be fatal.95

Attributed to chemical irritation by metabolites (e.g., acrolein) that accumulate in concentrated urine.1 2 3 38 59 111

Reduce bladder toxicity with conventional uroprophylaxis (e.g., high fluid intake, frequent urination) and use of fractionated ifosfamide dosage schedule, and concurrent administration of mesna.1 2 3 59 110

Examine urine prior to administration of each ifosfamide dose for presence of erythrocytes, which may precede hemorrhagic cystitis.a 95

If microscopic hematuria is present (>10 erythrocytes per high power field [HPF]), discontinue ifosfamide until complete resolution;a use vigorous oral or parenteral hydration as well as mesna for subsequent courses of ifosfamide.1 141

Discontinue ifosfamide or reduce dosage in patients who develop hematuria (>50 erythrocytes/HPF) while receiving usual dosages of ifosfamide in conjunction with mesna.95

Hematologic Effects

Dose-dependent myelosuppression, principally leukopenia and, to a lesser extent, thrombocytopenia, occurs commonly.1 2 3 58 59

Carefully monitor hematologic status during therapy; evaluate leukocyte and platelet counts and hemoglobin concentrations prior to and at appropriate intervals during therapy.1 2 3 58 59 Do not administer ifosfamide if leukocyte count <2000/mm3 and/or platelet count <50,000/mm3.1 In general, withhold subsequent courses until leukocyte count >4000/mm3 and platelet count >100,000/mm3.1

Use with caution in patients with compromised bone marrow reserve (i.e., leukopenia, granulocytopenia, extensive bone marrow metastases, prior radiation therapy, or prior therapy with other cytotoxic agents).1

Nervous System Effects

Risk of neurotoxicity, characterized by somnolence, confusion, encephalopathy, coma, confusion, mutism, auditory and/or visual hallucinations, and stupor.1 2 3 36 58 59 82 84 86 87 126 128

If one or more signs of serious neurotoxicity (i.e., somnolence, confusion, hallucinations, and/or coma) occur during therapy, discontinue therapy and institute appropriate supportive therapy.1 82 142 Effects generally are reversible and resolve within 2–4 days.1 2 3 36 58 59 80 82 83 84 85 128 Methylene blue has been used in management of ifosfamide-induced encephalopathy.126 127 161

Fetal/Neonatal Morbidity and Mortality

Can cause fetal harm; teratogenicity and embryotoxicity demonstrated in animals.a

If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.1

Major Toxicities

Renal Effects

Potentially serious nephrotoxicity (e.g., acute or chronic renal failure, Fanconi’s syndrome, renal tubular acidosis, nephrogenic diabetes insipidus); may be evidenced by aminoaciduria, glycosuria, proteinuria, cells or casts in the urine, increase in Scr or BUN, or decreased Clcr.1 3 19 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 96 124

Nephrotoxicity may develop during therapy or following discontinuance of the drug and can be reversible.62 64 67 68 69 70 72 74 76 77 122

Increased risk of nephrotoxicity associated with previous or concurrent cisplatin therapy and in patients with preexisting renal impairment, infiltrating renal tumor, or prior nephrectomy.3 19 59 62 64 67 68 73 74 76 110 124 125

Electrolyte Disturbances

Potentially fatal electrolyte abnormalities and/or acidosis reported.65 Closely monitor serum and urine chemistries (i.e, phosphorus, potassium, alkaline phosphatase) and other appropriate laboratory studies.1 62 65 68 77 141 If electrolyte abnormalities develop, institute appropriate therapy to correct any imbalance(s).1 62 65 68 77

General Precautions

Wound Healing

May interfere with normal wound healing.a

Specific Populations


Category D.a (See Fetal/Neonatal Morbidity and Mortality under Cautions.)


Distributed into milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established.1

Has been used in children 15 days to 17 years of age for the treatment of certain malignancies (e.g., Ewing’s sarcoma, rhabdomyosarcoma, Wilms’ tumor); adverse effects reported in these children appear to be similar to those reported in adults.34 61 62 75 121 122 133

Children ≤5 years of age may be more susceptible to ifosfamide-induced renal toxicity than older children or adults.3 62 64

Geriatric Use

Select dosage based on the clinical, renal, and hematologic response and tolerance of the patient; consider age-related decrease in hepatic, renal and/or hematopoietic function.1

Renal Impairment

Use with caution.a Possible increased risk of nephrotoxicity3 19 59 62 64 67 68 73 74 76 110 124 125 and neurotoxicity.1 2 3 36 58 59 82 86 (See Nervous System Effects under Cautions.)

Common Adverse Effects

Alopecia,1 59 nausea/vomiting,1 2 3 36 hematuria, CNS toxicity, infection, renal impairment.1 a

Interactions for Ifex/Mesnex Kit

Converted to active metabolites by mixed-function oxidases (cytochrome P-450 system).2 3 103 111

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (increased or decreased metabolism of ifosfamide); may result in increased or decreased conversion to active metabolites.2 79 96 141

Specific Drugs





Increased risk of nephrotoxicity 3 19 59 62 64 67 68 73 74 76 110 124 125

Associated with previous or concurrent cisplatin therapy3 19 59 62 64 67 68 73 74 76 110 124 125


Interacts chemically with urotoxic ifosfamide metabolites and precursors to prevent or decrease incidence and severity of bladder toxicity (e.g., hemorrhagic cystitis)2 3 62 63 71 95 108 141

Used for uroprotection2 3 62 63 71 95 108 141

Myelosuppressive agents

Possible additive hematologic toxicity1 2 3 7 10 11

Use concomitantly with caution; monitor carefully1 3

Ifex/Mesnex Kit Pharmacokinetics



Following IV administration, peak plasma concentrations of the principal alkylating metabolite are reached within 20–30 minutes.104



Widely distributed throughout the body, including the brain and CSF.3 98 99 Distributed into milk.1



Extensively metabolized, principally in the liver, to active and inactive metabolites.3 96 104 105

Metabolized to 4-hydroxyifosfamide (in equilibrium with acyclic tautomer aldoifosfamide),1 2 3 96 103 104 105 then to 4-ketoifosfamide.1 2 3 96 Also metabolized to chloroacetaldehyde, 2-dechloroethylifosfamide, and 3-dechloroethylifosfamide.1 2 3 96 103 104 105

Aldoifosfamide spontaneously splits into ifosfamide mustard (primary alkylating metabolite) and to acrolein1 2 3 96 103 and may be enzymatically metabolized to carboxyifosfamide.1 2 3 96

Elimination Route

Excreted principally in urine.1 2 3 96


Terminal half-life averages 4–8 hours in adults.3 85 86 104




Powder for Injection

20–25°C;1 106 113 protect from temperature >30°C.1


For information on systemic interactions resulting from concomitant use, see Interactions.


Solution CompatibilityHID


Dextrose 5% in Ringer’s injection

Dextrose 5% in sodium chloride 0.9%

Dextrose 5% in water

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

Sodium lactate 1/6 M

Drug Compatibility
Admixture CompatibilityHID




Cisplatin with etoposide

Epirubicin HCl




Y-Site CompatibilityHID


Allopurinol sodium


Amphotericin B cholesteryl sulfate complex



Caspofungin acetate


Doxorubicin HCl liposome injection

Etoposide phosphate


Fludarabine phosphate

Gallium nitrate

Gemcitabine HCl

Granisetron HCl


Melphalan HCl

Ondansetron HCl



Palonosetron HCl

Pemetrexed disodium

Piperacillin sodium–tazobactam sodium



Sodium bicarbonate



Topotecan HCl

Vinorelbine tartrate


Methotrexate sodium


  • Interferes with DNA replication and transcription of RNA, resulting in disruption of nucleic acid function.1 2 3 143 144 145 146

  • Also has immunosuppressive activity.112 144 146

Advice to Patients

  • Risk of bladder toxicity, myelosuppression, and neurotoxicity.a

  • Importance of informing clinicians if excessive sleepiness, confusion, or hallucinations occur.a

  • Advise that alopecia is likely.1

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1 Advise pregnant women of risk to the fetus.1

  • Importance of informing patients of other important precautionary information. (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.



Dosage Forms


Brand Names




1 g, For injection, for IV infusion, Ifosfamide (Ifex Kit)

100 mg/mL (1 g), Injection, Mesna (Mesnex) (with benzyl alcohol)

Ifex/Mesnex Kit

Bristol-Myers Squibb

100 mg/mL (1 g), Injection, Ifosfamide 100 mg/mL (1 g) Injection, Mesna (with benzyl alcohol)

Ifosfamide Injection/Mesna Injection Kit

3 g, For injection, for IV infusion, Ifosfamide (Ifex)

100 mg/mL (1 g), Injection, Mesna (Mesnex) (with benzyl alcohol)

Ifex/Mesnex Kit

Bristol-Myers Squibb

100 mg/mL (3 g), Injection, Ifosfamide 100 mg/mL (1 g) Injection, Mesna (with benzyl alcohol)

Ifosfamide Injection/Mesna Injection Kit

AHFS DI Essentials™. © Copyright 2020, Selected Revisions July 10, 2013. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.


1. Bristol-Myers Squibb. Ifex (ifosfamide for injection) prescribing information. Princeton, NJ; 1998 Jun.

2. Schoenike SE, Dana WJ. Ifosfamide and mesna. Clin Pharm. 1990; 9:179-91.

3. Dechant KL, Brogden RN, Pilkington T et al. Ifosfamide/mesna: a review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer. Drugs. 1991; 42:428-67.

4. Loehrer PJ, Lauer R, Roth BJ et al. Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide. Ann Int Med. 1988; 109:540-6.

5. Food and Drug Administration. List of orphan product designations & approvals. 1995 Apr.

6. Motzer RJ, Cooper K, Geller NL et al. The role of ifosfamide plus cisplatin-based chemotherapy as salvage therapy for patients with refractory germ cell tumors. Cancer. 1990; 66:2476-81.

7. Ghosn M, Droz JP, Theodore C et al. Salvage chemotherapy in refractory germ cell tumors with etoposide (VP-16) plus ifosfamide plus high-dose cisplatin. Cancer. 1988; 62:24-7.

8. Hansen HH, Rorth M. Lung cancer. In: Pinedo HM, Longo DL, Chabner BA eds. Cancer chemotherapy and biological response modifiers annual 14. 1993:442-3.

9. Anon. Drugs of choice for cancer chemotherapy. Med Lett Drugs Ther. 2000; 42:83-92.

10. Smith IE, Perren TJ, Ashley SA et al. Carboplatin, etoposide, and ifosfamide as intensive chemotherapy for small-cell lung cancer. J Clin Oncol. 1990; 8:899-905.

11. Thatcher N, Lind M, Stout R et al. Carboplatin, ifosfamide and etoposide with mid-course vincristine and thoracic radiotherapy for ”limited’ stage small cell carcinoma of the bronchus. Br J Cancer. 1989; 60:98-101.

12. Loehrer PJ, Rynard S, Ansari R et al. Etoposide, ifosfamide, and cisplatin in extensive small cell lung cancer. Cancer. 1992; 69:669-73.

13. Havemann K, Wolf M, Drings P et al. Experience of a german multicenter study group with ifosfamide in small cell lung cancer. Semin Oncol. 1989; 16:9-18.

14. Eberhardt W, Niederle N. Ifosfamide in non-small cell lung cancer: a review. Semin Oncol. 1992; 19:40-8.

15. de Schepper J, Hachimi-Idrissi S, Louis O et al. Bone metabolism and mineralization after cytotoxic chemotherapy including ifosfamide. Arch Dis Child. 1994; 71:346-8.

16. Crino L, Scagliotti GV, Ricci S et al. Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project. J Clin Oncol. 1999; 17:3522-30.

17. Cullen MH. Mitomycin, ifosfamide, and cisplatin in non-small cell lung cancer. Oncology. 1993; 50:31-4.

18. Krämer A, Goldschmidt H, Hahh U. Progressive renal failure in two breast cancer patients after high-dose ifosfamide. Lancet. 1994; 344:1569.

19. Garcia AA. Ifosfamide-induced fanconi syndrome. Ann Pharmacother. 1995; 29:590-1.

20. Sutton GP, Blessing JA, McGuire WP et al. Phase II trial of ifosfamide and mesna in patients with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy: a gynecologic oncology group study. Am J Obstet Gynecol. 1993; 168:805-7.

21. Coleman RE, Harper PG, Gallagher C et al. A phase II study of ifosfamide in advanced and relapsed carcinoma of the cervix. Cancer Chemother Pharmacol. 1986; 18:280-3.

22. Buxton EJ, Meanwell CA, Hilton C et la. Combination bleomycin, ifosfamide, and cisplatin chemotherapy in cervical cancer. J Natl Cancer Inst. 1989; 81:359-61.

23. Cervical cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2000 Aug.

24. Sutton GP, Blessing JA, Adcock L et al. Phase II study of ifosfamide and mesna in patients with previously-treated carcinoma of the cervix. Invest New Drugs. 1989; 7:341-3.

25. Murad AM, Triginelli SA, Ribolta JCL. Phase II trial of bleomycin, ifosfamide, and carboplatin in metastatic cervical cancer. J Clin Oncol. 1994; 12:55-9.

26. Ovarian epithelial cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2000 Oct.

27. Lorusso V, Catino A, Leone B et al. Carboplatin plus ifosfamide as salvage treatment of epithelial ovarian cancer: a pilot study. J Clin Oncol. 1993; 11:1952-6.

28. Sutton GP, Blessing JA, Homesley HD et al. Phase II trial of ifosfamide and mesna in advanced ovarian carcinoma: a gynecologic oncology group study. J Clin Oncol. 1989; 7:1672-6.

29. Markman M, Hakes T, Reichman B et al. Ifosfamide and mesna in previously treated advanced epithelial ovarian cancer: activity in platinum-resistant disease. J Clin Oncol. 1992; 10:243-8.

30. Uterine sarcoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Sep 1.

31. Sutton GP, Blessing JA, Rosenshein N et al. Phase II trial of ifosfamide and mesna in mixed mesodermal tumors of the uterus (a gynecologic oncology group study). Am J Obstet Gynecol. 1989; 161:309-12.

32. Sutton GP, Blessing JA, Barrett RJ et al. Phase II trial of ifosfamide and mesna in leiomyosarcoma of the uterus: a gynecologic oncology group study. Am J Obstet Gynecol. 1992; 166:556-9.

33. Ewing’s sarcoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Sep 1.

34. Meyer WH, Kun L, Marina N et al. Ifosfamide plus etoposide in newly diagnosed Ewing’s sarcoma of bone. J Clin Oncol. 1992; 10:1737-42.

35. Miser JS, Kinsella TJ, Triche TJ et al. Ifosfamide with mesna uroprotection and etoposide: an effective regimen in the treatment of recurrent sarcomas and other tumors of children and young adults. J Clin Oncol. 1987; 5:191-8.

36. Kung FH, Pratt CB, Vega RA et al. Ifosfamide/etoposide combination in the treatment of recurrent malignant solid tumors of childhood. Cancer. 1993; 71:1898-903.

37. Antman KH. Chemotherapy of advanced sarcomas of bone and soft tissue. Semin Oncol. 1992; 19:13-22.

38. Jürgens H, Exner U, Khl J et al. High-dose ifosfamide with mesna uroprotection in Ewing’s sarcoma. Cancer Chemother Pharmacol. 1989; 24:40-44S.

39. Demeocq F, Oberlin O, Benz-Lemoine E et al. Initial chemotherapy including ifosfamide in the management of Ewing’s sarcoma: preliminary results a protocol of the French Pediatric Oncology Society (SFOP). Cancer Chemother Pharmacol. 1989; 24:45-47S.

40. Osteosarcoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Sept 1.

41. Pratt CB. Ifosfamide studies for primary or recurrent pediatric malignant solid tumors and leukemia. Semin Oncol. 1990; 17:31-4.

42. Marti C, Kroner T, Remagen W et al. High-dose ifosfamide in advanced osteosarcoma. Cancer Treat Rep. 1985; 69:115-7.

43. Adult soft tissue sarcoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Sept 1.

44. Elias A, Ryan L, Sulkes A et al. Response to mesna, doxorubicin, ifosfamide, and dacarbazine in 108 patients with metastatic or unresectable sarcoma and no prior chemotherapy. J Clin Oncol. 1989; 7:1208-16.

45. Antman K, Crowley J, Balcerzak SP et al. An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J Clin Oncol. 1993; 11:1276-85.

46. Antman KH, Ryan L, Elias A et al. Response to ifosfamide and mesna: 124 previously treated patients with metastatic or unresectable sarcoma. J Clin Oncol. 1989; 7:126-31.

47. Childhood rhabdomyosarcoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Nov 30.

48. Magrath I, Sandlund J, Raynor A et al. A phase II study of ifosfamide in the treatment of recurrent sarcomas in young people. Cancer Chemother Pharmacol. 1986; 18:25-8S.

49. de Kraker J, Voute PA. Ifosfamide, mesna and vincristine in pediatric oncology. Cancer Treat Rev. 1983; 10:165-6.

50. Otten J, Flamant F, Rodary C et al. Treatment of rhabdomyosarcoma and other malignant mesenchymal tumours of childhood with ifosfamide + vincristine + dactinomycin (IVA) as front-line therapy (a SIOP study). Cancer Chemother Pharmacol. 1989; 24:30S.

51. Pappo AS, Etcubanas E, Santana VM et al. A phase II trial of ifosfamide in previously untreated children and adolescents with unresectable rhabdomyosarcoma. Cancer. 1993; 71:2119-25.

52. Testicular Cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Nov 30.

53. Non-small cell lung cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2000 Aug.

54. Small cell lung cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2000 Oct.

55. Cabanillas F. Ifosfamide combinations in lymphoma. Semin Oncol. 1990; 17:58-82.

56. Adult non-Hodgkin’s lymphoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Sept 1.

57. Armitage JO. Treatment of non-hodgkin’s lymphoma. N Engl J Med. 1993; 328:1023-30.

58. Antman KH, Elias A, Ryan L. Ifosfamide and mesna: response and toxicity at standard- and high-dose schedules. Semin Oncol. 1990; 17: 68-73.

59. Brade WP, Herdich K, Kachel-Fischer U et al. Dosing and side-effects of ifosfamide plus mesna. Cancer Res Clin Oncol. 1991; 117:5164-86.

60. Wilms’ tumor. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Sept 1.

61. Tournade MF, Lemerle J, Brunat-Mentigny M et al. Ifosfamide is an active drug in Wilms’ tumor: a phase II study conducted by the French Society of Pediatric Oncology. J Clin Oncol. 1988; 6:793-6.

62. Skinner R, Sharkey IA, Pearson ADJ et al. Ifosfamide, mesna, and nephrotoxicity in children. J Clin Oncol. 1993; 11:173-90.

63. Culine S, Ghosn M, Droz J. Inappropriate antidiuretic hormone secretion induced by ifosfamide. Eur J Cancer. 1990; 26:922.

64. Rossi R, Gödde A, Kleinbrand A et al. Unilateral nephrectomy and cisplatin as risk factors of ifosfamide-induced nephrotoxicity: analysis of 120 patients. J Clin Oncol. 1994; 12:159-65.

65. Husband DJ, Watkin SW. Fatal hypokalemia associated with ifosfamide/mesna chemotherapy. Lancet. 1988; :1116.

66. Newbury-Ecob RA, Nobel VW, Barbor PRH. Ifosfamide-induced fanconi syndrome. Lancet. 1989; :1328.

67. Rossi R, Kleinebrand A, Gdde A et al. Increased risk of ifosfamide-induced renal Fanconi’s syndrome after unilateral nephrectomy. Lancet. 1993; 341:755.

68. Burk CD, Restaino I, Kaplan BS et al. Ifosfamide-induced renal tubular dysfunction and rickets in children with Wilms tumor. J Pediatr. 1990; 117:331-5.

69. Skinner R, Pearson ADJ, Price L et al. Nephrotoxicity after ifosfamide. Arch Dis Childhood. 1990; 65:732-8.

70. Devalck C, Ismaili K, Ferster A. Acute ifosfamide-induced proximal tubular toxic reaction. J Pediatr. 1991; 118:325-6.

71. Goren MP, Wright RK, Horowitz ME et al. Ifosfamide-induced subclinical tubular nephrotoxicity despite mesna. Cancer Treat Rep. 1987; 71:127-30.

72. Willemse PHB, de Jong PE, Elema JD et al. Severe renal failure following high-dose ifosfamide and mesna. Cancer Chemother Pharmacol. 1989; 23:329-30.

73. Pratt CB, Meyer WH, Jenkins JJ et al. Ifosfamide, Fanconi’s syndrome, and rickets. J Clin Oncol. 1991; 9:1495-9.

74. Beckwith C, Flaharty KK, Cheung AK et al. Fanconi’s syndrome due to ifosfamide. Bone Marrow Transplant. 1989; 11:71-3.

75. Ifosfamide-induced fanconi’s syndrome with growth failure in a 2-year-old child. Am J Pediatr Hematol/Oncol. 1991; 13:39-41.

76. Rossi R, Ehrich JHH. Partial and complete de Toni-Debre-Fanconi syndrome after ifosfamide chemotherapy of childhood malignancy. Eur J Clin Pharmacol. 1993; 44:43-5S.

77. Heney D, Wheeldon J, Rushworth P et al. Progressive renal toxicity due to ifosfamide. Arch Dis Childhood. 1991; 66:966-70.

78. Patterson WP, Khojasteh A. Ifosfamide-induced renal tubular defects. Cancer. 1989; 63:649-51.

79. Simonian NA, Gilliam FG, Chiappa KH. Ifosfamide causes a diazepam-sensitive encephalopathy. Neurology. 1993; 43:2700-2.

80. Salloum E, Flamant F, Ghosh M et al. Irreversible encephalopathy with ifosfamide mesna. J Clin Oncol. 1987; 5:1303-4.

81. DiMaggio JR, Brown R, Baile WF et al. Hallucinations and ifosfamide-induced neurotoxicity. Cancer. 1994; 73:1509-14.

82. Miller LJ, Eaton VE. Ifosfamide-induced neurotoxicity: a case report and review of the literature. Ann Pharmacother. 1992; 26:183-7.

83. Danesh MM, De Giorgio CM, Beydoun SR et al. Ifosfamide encephalopathy. J Toxicol Clin Toxicol. 1989; 27:293-8.

84. Watkin SW, Husband DJ, Green JA et al. Ifosfamide Encephalopathy: a reappraisal. Eur J Clin Oncol. 1989; 25:1303-10.

85. Gieron MA, Barak LS, Estrada J. Severe encephalopathy associated with ifosfamide administration in two children with metastatic tumors. J Neuro-Oncol. 1988; 6:29-30.

86. Meanwell CA, Kelly KA, Blackledge G. Avoiding ifosfamide/mesna encephalopathy. Lancet. 1986; 2:406.

87. Anderson NR, Tandon DS. Ifosfamide extrapyramidal neurotoxicity. Cancer. 1991; 68:72-5.

88. Pallotta MG, Velazco A, Sadler A. Ifosfamide extrapyramidal neurotoxicity. Cancer. 1992; 70:2743-4.

89. Patel SR, Forman AD, Benjamin RS. High-dose ifosfamide-induced exacerbation of peripheral neuropathy. J Natl Cancer Inst. 1994; 86:305-6.

90. Teresi ME, Murry DJ, Cornelius AS. Ifosfamide-induced hyperpigmentation. Cancer. 1993; 71:2873-5.

91. Yule SM, Pearson AD, Craft AW. Ifosfamide-induced hyperpigmentation. Cancer. 1994; 73:240-1.

92. Baker WJ, Fistel SJ, Jones RV et al. Interstitial pneumonitis associated with ifosfamide therapy. Cancer. 1990; 65:2217-21.

93. Choonara IA, Overend M, Bailey CC. Blurring of vision due to ifosfamide. Cancer Chemother Pharmacol. 1987; 20:349.

94. Quezado ZMN, Wilson WH, Cunnion RE et al. High-dose ifosfamide is associated with severe, reversible cardiac dysfunction. Ann Int Med. 1993; 188:31-6.

95. Bristol-Myers Squibb. Mesnex (mesna) injection prescribing information. Princeton, NJ; 1998 Mar.

96. Wagner T. Ifosfamide clinical pharmacokinetics. Clin Pharmacokinet. 1994; 26:439-56.

97. Pearcey R, Calvert R, Mehta A. Disposition of ifosfamide in patients receiving ifosfamide infusion therapy for the treatment of cervical carcinoma. Cancer Chemother Pharmacol. 1988; 22:353-5.

98. Allen LM, Creaven PJ, Nelson RL. Studies on the human pharmacokinetics of isophosphamide (NSD-109724). Cancer Treat Rep. 1976; 60:451-8.

99. Allen LM, Creaven PJ. Pharmacokinetics of ifosfamide. Clin Pharmacokinet. 1994; 26:439-56.

100. Lind MJ, Margison JM, Cerny T et al. Prolongation of ifosfamide elimination half-life in obese patients due to altered drug distribution. Cancer Chemother Pharmacol. 1989; 25:139-42.

101. Lind MJ, Margison JM, Cerny T et al. The effect of age on the pharmacokinetics of ifosfamide. Br J Clin Pharmacol. 1990; 30:140-3.

102. Lewis LD, Fitzgerald DL, Mohan P et al. The pharmacokinetics of ifosfamide given as short and long intravenous infusions in cancer patients. Br J Clin Pharmacol. 1991; 31:77-82.

103. Kaijser GP, Korst A, Beijnen JH et al. The analysis of ifosfamide and its metabolites (review). Anticancer Res. 1993; 13:1311-24.

104. Kurowski V, Cerny T, Küpfer A et al. Metabolism and pharmacokinetics of oral and intravenous ifosfamide. J Cancer Res Clin Oncol. 1991; 117:148-53.

105. Kurowski V, Wagner T. Comparative pharmacokinetics of ifosfamide, 4-hydroxyifosfamide, chloracetaldehyde, and 2- and 3-dechlorethylifosfamide in patients on fractionated intravenous ifosfamide therapy. Cancer Chemother Pharmacol. 1993; 33:36-42.

106. US Dept. of Health and Human Services. Ifosfamide pharmaceutical data. In: NCI investigational drugs. National Institutes of Health. 1987.

107. Boddy AV, Yule SM, Wyllie R et al. Pharmacokinetics and metabolism of ifosfamide administered as a continuous infusion in children. Cancer Res. 1993; 53:3758-64.

108. Mead Johnson. Mesnex (mesna injection) dosing and administration guide. Princeton, NJ; 1989 Jun.

109. Mesna. In: Trissel LA. Handbook on injectable drugs. 8th ed. Bethesda, MD. American Society of Hospital Pharmacists; 1994:664-6.

110. Goren MP, Wright RK, Pratt CB et al. Potentiation of ifosfamide neurotoxicity, hematotoxicity, and tubular nephrotoxicity by prior cis-diamminedichloroplatinum(II) therapy. Can Res. 1987; 47:1457-60.

111. DeVita VT JR, Hellman S, Rosenberg SA, eds. Cancer: principles & practice of oncology. 4th 3d. Philadelphia, PA. JB Lippincott Company. 1993: 400-9,1473-9.

112. Holland JF, Frei E, Bast RC et al, eds. Cancer medicine. 3rd ed. Philadelphia, PA. Lea & Febiger. 1993:733-43.

113. The United States pharmacopeia, 23rd rev, and The national formulary, 18th ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1995:

114. Ifosfamide. In: Trissel LA. Handbook on injectable drugs. 8th ed. Bethesda, MD. American Society of Hospital Pharmacists; 1994:S73-6.

115. Le Cesne A, Antoine E, Spielmann M et al. High-dose ifosfamide: circumvention of resistance to standard-dose ifosfamide in advanced soft tissue sarcomas. J Clin Oncol. 1995; 13:1600-8.

116. Loehrer PJ, Williams SD, Nichols CR et al. Clinical trials with ifosfamide: the Indiana University experience. Semin Oncol. 1992; 19(Suppl 1):35-9.

117. Santoro A, Tursz T, Mouridsen H et al. Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 1995; 13:1537-45.

118. Edmonson JH. Needed: qualitative improvement in antisarcoma therapy. J Clin Oncol. 1995; 13:1531-3.

119. Childhood non-Hodgkin’s lymphoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Sept 1.

120. Furusawa S, Fujimura T, Sasaki K et al. Potentiation of ifosfamide toxicity by chlordiazepoxide, diazepam and oxazepam. Chem Pharm Bull. 1989; 37:3420-2.

121. Valdivieso Torres MJ, Lopez Perez J, Melero C et al. Ifosfamide-induced renal tubular defect. Med Pediatr Oncol. 1994; 22:144-6.

122. Hanquinet S, Wouters M, Devalck C et al. Increased renal parenchymal echogenicity in ifosfamide-induced renal fanconi syndrome. Med Pediatr Oncol. 1995; 24:116-8.

123. Ashraf MS, Brady J, Breatnach F et al. Ifosfamide nephrotoxicity in pediatric cancer patients. Eur J Pediatr. 1994; 155:90-4.

124. Jones DP, Chesney RW. Renal toxicity of cancer chemotherapeutic agents in children: ifosfamide and cisplatin. Curr Sci. 1995; 7:208-13.

125. Raney B, Ensign LG, Foremen J et al. Renal toxicity of ifosfamide in pilot regimens of the intergroup rhabdomyosarcoma study for patients with gross residual tumor. Am J Pediatr Hematol Oncol. 1994; 16:286-95.

126. Kpfer A, Aeschlimann C, Wermuth B et al. Prophylaxis and reversal of ifosfamide encephalopathy with methylene-blue. Lancet. 1994; 343:763-4.

127. Zulian GB, Tullen E, Maton B. Methylene blue for ifosfamide-associated encephalopathy. N Engl J Med. 1995; 332:1239-40.

128. Bruggers CS, Friedman HS, Tien R et al. Cerebral atrophy in an infant following treatment with ifosfamide. Med Pediatr Oncol. 1994; 23:380-3.

129. Heim M, Fiene R, Schick E at al. Central nervous side effects following ifosfamide monotherapy of advanced renal carcinoma. J Cancer Res Clin Oncol. 1981; 100:113-6.

130. Izraeli S, Adamson PC, Blaney SM et al. Acute pancreatitis after ifosfamide therapy. Cancer. 1994; 74:1267-8.

131. Mateu J, Alzamera M, Franco M et al. Ifosfamide extravasation. Ann Pharmacother. 1994; 28:1243-4.

132. Ettinger DS. The place of ifosfamide in chemotherapy of small cell lung cancer: the Eastern Cooperative Oncology Group experience and a selected literature update. Semin Oncol. 1995; 22:23-7.

133. Marina NM, Wilimas JA, Meyer WH et al. Refining therapeutic strategies for patients with resistant Wilms’ tumor. Am J Pediatr Hematol/Oncol. 1994; 16:296-300.

134. Non-small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. BMJ. 1995; 311:899-909.

135. NIH Consensus Development Panel on Ovarian Cancer. NIH consensus conference on ovarian cancer: screening, treatment, and follow-up. JAMA. 1995; 273:491-7.

136. Petru E, Schmähl D. Second malignancies–risk reduction. Cancer Treat Rev. 1987; 14:337-43.

137. Food and Drug Administration. Labeling and prescription drug advertising; content and format for labeling for human prescription drugs. 21 CFR Parts 201 and 202. Final Rule. [Docket No. 75N-0066] Fed Regist. 1979; 44:37434-67.

138. Department of Health and Human Services, Food and Drug Administration. Subpart B—Labeling requirements for prescription drugs and/or insulin. (21 CFR Ch. 1(4-1-87 Ed.)). 1987:18-24.

139. Shaw IC, Graham MI. Mesna—a short review. Cancer Treat Rev. 1987; 14:67-86.

140. Burkert H. Clinical overview of mesna. Cancer Treat Rev. 1983; 10:175-81.

141. Reviewers’ comments (personal observations).

142. Bristol-Myers Squibb, Princeton, NJ: Personal communication.

143. Witte RS, Elson P, Bono B et al. Eastern Cooperative Oncology Group phase II trial of ifosfamide in the treatment of previously treated advanced urothelial carcinoma. J Clin Oncol. 1997; 15:589-93.

144. McCaffrey J, Hilton S, Mazumdar M et al. A phase II trial of ifosfamide, paclitaxel and cisplatin (ITP) in patients (pts) with advanced urothelial tract tumors. Proc Am Soc Clin Oncol. 1996; 15:251.

145. Dreicer R, Propert KJ, Roth BJ et al. Vinblastine, ifosfamide, and gallium nitrate—an active new regimen in patients with advanced carcinoma of the urothelium: a phase II trial of the Eastern Cooperative Oncology Group (E5892). Cancer. 1997; 79:110-4.

146. Einhorn LH, Roth BJ, Ansari R et al. Phase II trial of vinblastine, ifosfamide, and gallium combination chemotherapy in metastatic urothelial carcinoma. J Clin Oncol. 1994; 12:2271-6.

147. Schmidt AS, Ruther U, Eisenberger F. First line therapy with ifosfamide and etoposide for the treatment of advanced bladder cancer. J Urol. 1993; 149:318.

148. Stadler WM, Kuzel T, Roth B et al. Phase II study of single-agent gemcitabine in previously untreated patients with metastatic urothelial cancer. J Clin Oncol. 1997; 15:3394-8.

149. Roth BJ. Ifosfamide in the treatment of bladder cancer. Semin Oncol. 1996; 23(Suppl 6):50-5.

150. Loehrer PJ Sr, Ansari R, Gonin R et al. Cisplatin plus etoposide with and without ifosfamide in extensive small-cell lung cancer: a Hoosier Oncology Group study. J Clin Oncol. 1995; 13:2594-9.

151. Sculier JP, Paesmans M, Thiriaux J et al. Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. J Clin Oncol. 1998; 16:1388-96.

152. Omura GA, Blessing JA, Vaccarello L et al. Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1997; 15:165-71.

153. Kumar L, Pokharel YH, Kumar S et al. Single agent versus combination chemotherapy in recurrent cervical cancer. J Obstet Gynaecol Res. 1998; 24:401-9.

154. Buxton EJ. Experience with bleomycin, ifosfamide, and cisplatin in primary and recurrent cervical cancer. Semin Oncol. 1992; 19(2 Suppl 5):9-18.

155. Alberts DS, Kronmal R, Baker LH et al. Phase II randomized trial of cisplatin chemotherapy regimens in the treatment of recurrent or metastatic squamous cell cancer of the cervix: a Southwest Oncology Group Study. J Clin Oncol. 1987; 5:1791-5.

156. Thigpen T, Vance R, Khansur T et al. The role of ifosfamide and systemic therapy in the management of carcinoma of the cervix. Semin Oncol. 1996; 23(3 Suppl 6):56-64.

157. Meanwell CA, Mould JJ, Blackledge G et al. Phase II study of ifosfamide in cervical cancer. Cancer Treat Rep. 1986; 70:727-30.

158. Sutton GP, Blessing JA, DiSaia PJ et al. Phase II study of ifosfamide and mesna in nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1993; 49:48-50.

159. Reviewers’ comments (personal observations) on cervical cancer.

160. Sicor. Ifosfamide injection prescribing information. Irvine, CA; 2004 Feb.

161. Patel PN. Methylene blue for management of Ifosfamide-induced encephalopathy. Ann Pharmacother. 2006; 40:299-303.

a. Bristol Myers Squibb. Ifex (ifosfamide for injection) prescribing information. Princeton, NJ; 2002 Nov.

b. AHFS drug information 2005. McEvoy GK, ed. Ifosfamide. Bethesda, MD: American Society of Health-System Pharmacists; 2005:1046-51.

c. Treatment Guidelines from the Medical Letter Drugs of Choice for Cancer. Abramowicz M, ed. New Rochelle, NY: The Medical Letter, Inc.; 2003 Mar: 41-51.

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:650-3.