Myelosuppression, Immunosuppression, and Infections Treatment with ifosfamide may cause myelosuppression and significant suppression of immune responses, which can lead to severe infections. Fatal outcomes of ifosfamide-associated myelosuppression have been reported. Ifosfamide-induced myelosuppression can cause leukopenia, neutropenia, thrombocytopenia (associated with a higher risk of bleeding events), and anemia. The nadir of the leukocyte count tends to be reached approximately during the second week after administration. When ifosfamide is given in combination with other chemotherapeutic/hematotoxic agents and/or radiation therapy, severe myelosuppression is frequently observed. The risk of myelosuppression is dose-dependent and is increased with administration of a single high dose compared with fractionated administration. The risk of myelosuppression is also increased in patients with reduced renal function. Severe immunosuppression has led to serious, sometimes fatal, infections. Sepsis and septic shock also have been reported. Infections reported with ifosfamide include pneumonias, as well as other bacterial, fungal, viral, and parasitic infections. Latent infections can be reactivated. In patients treated with ifosfamide, reactivation has been reported for various viral infections. Infections must be treated appropriately. Antimicrobial prophylaxis may be indicated in certain cases of neutropenia at the discretion of the managing physician. In case of neutropenic fever, antibiotics and/or antimycotics must be given. Close hematologic monitoring is recommended. White blood cell (WBC) count, platelet count and hemoglobin should be obtained prior to each administration and at appropriate intervals after administration. Unless clinically essential, ifosfamide should not be given to patients with a WBC count below 2000/microliter and/or a platelet count below 50,000/microliter. Ifosfamide should be given cautiously, if at all, to patients with presence of an infection, severe immunosuppression or compromised bone marrow reserve, as indicated by leukopenia, granulocytopenia, extensive bone marrow metastases, prior radiation therapy, or prior therapy with other cytotoxic agents.Central Nervous System Toxicity, Neurotoxicity Administration of ifosfamide can cause CNS toxicity and other neurotoxic effects. The risk of CNS oxicity and other neurotoxic effects necessitates careful monitoring of the patient. Neurologic manifestations consisting of somnolence, confusion, hallucinations, blurred vision, psychotic ehavior, extrapyramidal symptoms, urinary incontinence, seizures, and in some instances, coma, ave been reported following ifosfamide therapy. There have also been reports of peripheral europathy associated with ifosfamide use. fosfamide neurotoxicity may become manifest within a few hours to a few days after first dministration and in most cases resolves within 48 to 72 hours of ifosfamide discontinuation. Symptoms may persist for longer periods of time. Supportive therapy should be maintained until heir complete resolution. Occasionally, recovery has been incomplete. Fatal outcomes of CNS oxicity have been reported. Recurrence of CNS toxicity after several uneventful treatment courses as been reported. If encephalopathy develops, administration of ifosfamide should be discontinued. Due to the potential for additive effects, drugs acting on the CNS (such as antiemetics, sedatives, arcotics, or antihistamines) must be used with particular caution or, if necessary, be discontinued n case of ifosfamide-induced encephalopathy. Manifestations of CNS toxicity may impair a patient’s ability to operate an automobile or other eavy machinery. Renal and Urothelial Toxicity and Effects fosfamide is both nephrotoxic and urotoxic. Women should not become pregnant and men should not father a child during therapy with osfamide. Further, men should not father a child for up to 6 months after the end of therapy. If his drug is used during pregnancy, or if the patient becomes pregnant while taking this drug or fter treatment, the patient should be apprised of the potential hazard to a fetus. Effects on Fertility fosfamide interferes with oogenesis and spermatogenesis. Amenorrhea, azoospermia, and sterility both sexes have been reported.
