Fosfa Warnings

Should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Urotoxic side effects, especially hemorrhagic cystitis, as well as CNS toxicities such as confusion and coma have been associated with the use of Ifosfamide for injection and when these occur, cessation of Ifosfamide therapy may be recommended. Severe myelosuppression has been reported in studies.
It is highly recommended that the doctor keeps a check on the progress of treatment and unwanted effects, during regular visits. While on treatment with Ifosfamide and after cessation of treatment, it is strictly recommended to refrain from any immunizations (vaccinations) without the doctor's approval. Ifosfamide may lower the body's resistance and there is a chance of contracting infection the immunization is meant to prevent. In addition, relatives of the patient living in the same house should not take oral polio vaccine since there is a chance of passing the polio virus; hence avoid persons who have taken oral polio vaccine within the past several months, do not get close to them and stay in the same room for very long. If these precautions cannot be taken, one should consider wearing a protective face mask that covers the nose and mouth.
The treating doctor should be informed immediately for unusual bleeding or bruising, black tarry stools, blood in urine or stools and pinpoint red spots on the skin. Care should be taken while using a regular toothbrush, dental floss, or toothpick.
Ifosfamide should be given cautiously to patients with any of the following conditions like Leukopenia/Thrombocytopenia/Tumour cell infiltration of the bone marrow/Prior radiotherapy/Prior treatment with other antineoplastic agents/Brain metastases and advanced cerebral arteriosclerosis/Impaired renal function/Impaired hepatic function/In the presence of known infections and or Abnormal serum creatinine and serum albumin levels. Because Ifosfamide may exert a suppressive action in immune mechanisms, the interruption or modification of dosage should be considered for patients who develop bacterial, fungal or viral infections. This is especially true for patients receiving concomitant steroid therapy, since infections in some of these patients have been fatal. Ifosfamide may cause significant neurologic, renal and hematologic toxicities which may prove fatal despite careful monitoring prior to and during therapy. Prior to initiating treatment, it is necessary to exclude or correct any obstruction of the efferent urinary tract, cystitis, infections, and electrolyte imbalances. Urinary sediment should be examined at regular intervals. Extra care is required in unilaterally nephrectomised patients, in patients with impaired renal function, and in patients pretreated with nephrotoxic drugs (e.g., cisplatin) who obviously tolerate high doses of Ifosfamide less well. Ifosfamide should not be given until three months after the nephrectomy. Additional caution is also advisable in patients treated concomitantly with drugs having nephrotoxic potential (e.g., aminoglycosides and amphotericin B). Careful monitoring is also required for patients with cerebral metastases, as Ifosfamide has been associated with several CNS symptoms. Leukocyte, erythrocyte and platelet counts should be carried out at regular intervals. There is normally a reduction in the leukocyte count beginning approximately by day 5. The nadir, depending on dosage and baseline count is usually reached after 8-10 days. Recovery occurs after 10-14 days and is usually complete after 2-3 weeks. Neurologic manifestations consisting of somnolence, confusion, hallucinations and, in some instances, coma have been reported following Ifosfamide therapy. In the case of Ifosfamide-induced CNS symptoms, drugs acting on the CNS (e.g., antiemetics and narcotics) should be discontinued, if possible, or used with caution. The occurrence of these symptoms requires discontinuing Ifosfamide therapy. These symptoms have usually been reversible and supporting therapy should be maintained until their resolution.
Ifosfamide should be given cautiously to patients with impaired renal function as well as to those with compromised bone marrow reserve, as indicated by: leukopenia, granulocytopenia, extensive bone marrow metastases, prior radiation therapy, or prior therapy with other cytotoxic agents.
During treatment, the patient's hematologic profile (particularly neutrophils and platelets) should be monitored regularly to determine the degree of hematopoietic suppression. Urine should also be examined regularly for red cells which may precede hemorrhagic cystitis.
Wound healing: Ifosfamide may interfere with normal wound healing.
Carcinogenesis, Mutagenesis, Impairment of fertility: Ifosfamide has been shown to be carcinogenic in rats, with female rats showing a significant incidence of leiomyosarcomas and mammary fibroadenomas. 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.
Use in Pregnancy: "Category D".
Use in Lactation: Ifosfamide is excreted in breast milk. Because of the potential for serious adverse events and the tumorigenicity shown for Ifosfamide in animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Use in Children: Safety and effectiveness in pediatric patients have not been established.