Ifosfamide

Pregnancy Category D. Ifosfamide can cause fetal harm when given to a pregnant woman. Fetal growth retardation and neonatal anemia have been reported following exposure to ifosfamide-containing chemotherapy regimens during pregnancy. Animal studies indicate that ifosfamide is capable of causing gene mutations and chromosomal damage in living organisms. In pregnant mice, resorptions increased and anomalies were present at day 19 after a 30 mg/m2 dose of ifosfamide was given on day 11 of gestation. Embryo lethal effects were observed in rats following administration of 54 mg/m2 doses of ifosfamide from the 6th through the 15th day of gestation, and embryotoxic effects were apparent after mothers received 18 mg/m2 doses over the same period. Ifosfamide is embryotoxic to rabbits receiving 88 mg/m2 per day doses from the 6th through the 18th day after mating, and the number of anomalies was also significantly increased over the control group.

Women should not become pregnant and men should not father a child during therapy with ifosfamide. Men should also not father a child for up to 6 months after the end of therapy. If this drug is used during pregnancy, or if the patient becomes pregnant while taking it or after treatment, she should be told of the potential hazard to a fetus.

Nursing mothers: ifosfamide is excreted in breast milk. Because of the potential for serious adverse events and the tumor causing potential shown for ifosfamide in animal studies, a decision should be made whether to stop nursing or stop the drug, taking into account how important the drug is to the mother. Women must not breastfeed during treatment with ifosfamide.

Pediatric use: safety and effectiveness have not been established in pediatric patients.

Geriatric use (section 8.5): in general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased liver, kidney, or heart function, and of other illness or drug therapy in this age group. A study of patients 40 to 71 years of age indicated that the elimination half life appears to increase with advancing age. This apparent increase in half life appeared to be related to an increase in the volume of distribution of ifosfamide with age. No significant changes in total plasma clearance, or in renal or non renal clearance, with age were reported. Ifosfamide and its metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired kidney function. Because elderly patients are more likely to have decreased kidney function, care should be taken in dose selection, and it may be useful to monitor kidney function.

This is discussed further under use in patients with renal impairment (section 8.6).