Pregnancy & Lactation : הריון/הנקה

4.6 Pregnancy and lactation
Pregnancy
The administration of ifosfamide during organogenesis has been shown to have a fetotoxic effect in mice, rats, and rabbits and therefore may cause fetal damage when administered to pregnant women.
There are only very limited data available on the use of ifosfamide during pregnancy in humans. Fetal growth retardation and neonatal anemia have been reported following exposure to ifosfamide-containing chemotherapy regimens during pregnancy. Multiple congenital deviations have been reported after use during the first trimester of pregnancy.
Animal data generated with cyclophosphamide, another oxazaphosphorine cytotoxic agent suggest that an increased risk of failed pregnancy and malformations may persist after discontinuation of the agent as long as oocytes/follicles exist that were exposed to the agent during any of their maturation phases.
In addition, exposure to cyclophosphamide has been reported to cause miscarriage, malformations (following exposure during the first trimester), and neonatal effects, including leukopenia, pancytopenia, severe bone marrow hypoplasia, and gastroenteritis.
Based on the results of animal studies, human case reports and the substance's mechanism of action, the use of Ifosfamide during pregnancy, particularly in the first trimester, is advised against.
In every individual case, the benefits of the treatment will have to be weighed against possible risks for the fetus.
If ifosfamide is used during pregnancy, or if the patient becomes pregnant while taking this drug or after treatment, the patient should be apprised of the potential hazard to a fetus.

Breast-feeding
Ifosfamide is passed into the breast milk and may cause neutropenia, thrombocytopenia, low hemoglobin concentrations and diarrhea in children. Ifosfamide is contra-indicated for breast- feeding (see section 4.3).

Fertility
Ifosfamide interferes with oogenesis and spermatogenesis. It may cause sterility in both sexes.
Development of sterility appears to depend on the dose of ifosfamide, duration of therapy, and state of gonadal function at the time of treatment.
Ifosfamide may cause transient or permanent amenorrhea in women and oligospermia or azoospermia in men.

Female Patients
Women treated with ifosfamide should be informed prior to treatment about the possibility to save and preserve their eggs.
The risk of permanent chemotherapy-induced amenorrhea is increased in older women.
Girls treated with ifosfamide during prepubescence may develop secondary sexual characteristics normally and have regular menses.
Girls treated with ifosfamide during prepubescence subsequently have conceived.
Girls who have retained ovarian function after completing treatment are at increased risk of developing premature menopause.

Male Patients
Men treated with Ifosfamide should be informed prior to treatment about the possibility to save pre-produced sperm kept in proper conditions.
Sexual function and libido generally are unimpaired in these patients.
Boys treated with ifosfamide during prepubescence may develop secondary sexual characteristics normally, but may have oligospermia or azoospermia.
Some degree of testicular atrophy may occur.
Azoospermia may be reversible in some patients, though the reversibility may not occur for several years after cessation of therapy.
Men treated with ifosfamide have subsequently fathered children.

Genotoxicity
Ifosfamide is genotoxic and mutagenic in male and female germ cells. Therefore, women should not become pregnant and men should not father a child during therapy with ifosfamide.
Women treated with ifosfamide should take contraceptive measures for at least 1 year after discontinuation of ifosfamide therapy.
Men should not father a child for up to 6 months after the end of therapy.
Sexually active women and men should use effective methods of contraception during these periods of time.