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IFEX

Brand Name:	IFEX	Trade Name:	ifosfamide
FDA Approved For:	IFEX, used in combination with certain other approved antineoplastic agents, is indicated for third line chemotherapy of germ cell testicular cancer. It should ordinarily be used in combination with a prophylactic agent for hemorrhagic cystitis, such as mesna.	Pediatric Use:	Safety and effectiveness in pediatric patients have not been established.
Carcinogen:	Ifosfamide has been shown to be carcinogenic in rats, with female rats showing a significant incidence of leiomyosarcomas and mammary fibroadenomas.	Mutagen:	The mutagenic potential of ifosfamide has been documented in bacterial systems in vitro and mammalian cells in vivo . In vivo , ifosfamide has induced mutagenic effects in mice and Drosophila melanogaster germ cells, and has induced a significant increase in dominant lethal mutations in male mice as well as recessive sex-linked lethal mutations in Drosophila.
Manufacturer and/or Distributor:	Bristol-Myers Squibb

Adverse Reactions:

In patients receiving IFEX as a single agent, the dose-limiting toxicities are myelosuppression and urotoxicity. Dose fractionation, vigorous hydration, and a protector such as mesna can significantly reduce the incidence of hematuria, especially gross hematuria, associated with hemorrhagic cystitis. At a dose of 1.2 g/m 2 daily for 5 consecutive days, leukopenia, when it occurs, is usually mild to moderate. Other significant side effects include alopecia, nausea, vomiting, and central nervous system toxicities. (See Table) Hematologic Toxicity: Myelosuppression was dose related and dose limiting. It consisted mainly of leukopenia and, to a lesser extent, thrombocytopenia. A WBC count < 3000/µL is expected in 50% of the patients treated with IFEX single agent at doses of 1.2 g/m 2 per day for 5 consecutive days. At this dose level, thrombocytopenia (platelets < 100,000/µL) occurred in about 20% of the patients. At higher dosages, leukopenia was almost universal, and at total dosages of 10-12 g/m 2 /cycle, one half of the patients had a WBC count below 1000/µL and 8% of patients had platelet counts less than 50,000/µL. Myelosuppression was usually reversible and treatment can be given every 3 to 4 weeks. When IFEX is used in combination with other myelosuppressive agents, adjustments in dosing may be necessary. Patients who experience severe myelosuppression are potentially at increased risk for infection. Anemia has been reported as part of postmarketing surveillance. Digestive System: Nausea and vomiting occurred in 58% of the patients who received IFEX. They were usually controlled by standard antiemetic therapy. Other gastrointestinal side effects include anorexia, diarrhea, and in some cases, constipation. Urinary System: Urotoxicity consisted of hemorrhagic cystitis, dysuria, urinary frequency and other symptoms of bladder irritation. Hematuria occurred in 6% to 92% of patients treated with IFEX. The incidence and severity of hematuria can be significantly reduced by using vigorous hydration, a fractionated dose schedule and a protector such as mesna. At daily doses of 1.2 g/m 2 for 5 consecutive days without a protector, microscopic hematuria is expected in about one half of the patients and gross hematuria in about 8% of patients. Renal toxicity occurred in 6% of the patients treated with ifosfamide as a single agent. Clinical signs, such as elevation in BUN or serum creatinine or decrease in creatinine clearance, were usually transient. They were most likely to be related to tubular damage. One episode of renal tubular acidosis which progressed into chronic renal failure was reported. Proteinuria and acidosis also occurred in rare instances. Metabolic acidosis was reported in 31% of patients in one study when IFEX was administered at doses of 2.0 to 2.5 g/m 2 /day for 4 days. Renal tubular acidosis, Fanconi syndrome, renal rickets and acute renal failure have been reported. Close clinical monitoring of serum and urine chemistries including phosphorus, potassium, alkaline phosphatase and other appropriate laboratory studies is recommended. Appropriate replacement therapy should be administered as indicated. Central Nervous System: CNS side effects were observed in 12% of patients treated with IFEX. Those most commonly seen were somnolence, confusion, depressive psychosis, and hallucinations. Other less frequent symptoms include dizziness, disorientation, and cranial nerve dysfunction. Seizures and coma with death were occasionally reported. The incidence of CNS toxicity may be higher in patients with altered renal function. Other: Alopecia occurred in approximately 83% of the patients treated with IFEX as a single agent. In combination, this incidence may be as high as 100%, depending on the other agents included in the chemotherapy regimen. Increases in liver enzymes and/or bilirubin were noted in 3% of the patients. Other less frequent side effects included phlebitis, pulmonary symptoms, fever of unknown origin, allergic reactions, stomatitis, cardiotoxicity, and polyneuropathy. )

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