Animal studies have revealed evidence of teratogenicity and embryofetal toxicity. After daily IV injections to pregnant mice during organogenesis, the incidence of fetal malformations (cleft palate, protruding tongue, enlarged/misshaped kidney, fused lumbar vertebra) increased at doses (based on body surface area [BSA]) 0.03 times the human dose of 500 mg/m2. At doses (based on BSA) at least 0.0012 times the 500 mg/m2 human dose, dose-dependent increases in developmental delays (incomplete ossification of talus and skull bone, decreased fetal weight) were observed. There are no controlled data in human pregnancy.

This drug may impair fertility in males of reproductive potential; it is not known whether effects on fertility are reversible.

AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

Use should be avoided.
-According to some authorities: This drug should not be used during pregnancy unless clearly needed and the benefit outweighs the risk to the fetus.

AU TGA pregnancy category: D
US FDA pregnancy category: Not assigned.

Risk summary: Based on animal data and its mechanism of action, this drug can cause fetal harm when administered to a pregnant woman; no data available on use of this drug in pregnant women.

Comments:
-This drug can have genetically damaging effects.
-If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus.
-According to some authorities: Pregnancy status of patients of childbearing potential should be verified before starting this drug.
-Due to the potential for genotoxicity:
---Patients of childbearing potential should be advised to use effective contraception during therapy and for 6 months after the last dose.
---Male patients with female partners of childbearing potential should be advised to use effective contraception during therapy and for 3 months after the last dose; according to some authorities, sexually mature males are advised to use effective contraceptive measures and not to father a child during therapy and up to 3 months thereafter.
-Local protocol should be consulted regarding contraception timing.
-Due to the possibility of irreversible infertility, men are advised to seek counseling on sperm storage before starting this drug.

See references

Breastfeeding is not recommended during use of this drug and for 1 week after the last dose.
-According to some authorities: Use is contraindicated.

Excreted into human milk: Unknown
Excreted into animal milk: Data not available

Comments:
-The effects in the nursing infant are unknown.
-Most sources consider breastfeeding to be contraindicated during maternal high-dose antineoplastic drug therapy.
-Chemotherapy may adversely affect the normal microbiome and chemical makeup of breast milk.
-Patients who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant.

See references