Animal studies have revealed evidence of embryofetal lethality. Pregnant cynomolgus monkeys received 5 weekly IV injections (1 or 3 mg/kg) starting on day 20 of gestation; a non-dose dependent increase in pregnancy loss (abortions) was seen at both doses. Serum exposure (Cmax) in pregnant monkeys at the lower dose (1 mg/kg) was 158 times the human exposure at the maximum recommended intravitreal dose (6 mg every 4 weeks); this study did not find a no observed adverse effect level (NOAEL). There are no controlled data in human pregnancy.

The effects of this drug on human fertility have not been studied; it is not known if this drug can affect reproduction capacity. Based on the mechanism of action, this drug may present a risk to reproductive capacity.

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.

This drug should not be used during pregnancy unless the benefit outweighs the risk to the fetus.

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

Risk summary: Based on the mechanism of action of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) inhibitors, there is a potential risk to female reproductive capacity and to embryofetal development.

Comment:
-Patients of childbearing potential should be advised to use effective contraception before the initial dose, during therapy, and for at least 3 months after the last dose.

See references

Caution is recommended, particularly while breastfeeding newborn or preterm infants; an alternative agent with more breastfeeding information may be preferred.

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

Comments:
-No information is available on the clinical use of this drug during breastfeeding.
-Developmental and health benefits of breastfeeding should be considered as well as the mother's clinical need for this drug.
-The effects in the nursing infant are unknown; potential side effects in the breastfed child due to this drug should be considered.

Since this drug is a large protein molecule with a molecular weight of about 149 kilodaltons, the amount in milk is likely to be very low. In addition, the infant's gastrointestinal tract is likely to partially destroy this drug; absorption by the infant would probably be minimal.

This drug inhibits vascular endothelial growth factor (VEGF). Because there is VEGF in human milk and VEGF is thought to facilitate maturation of the infant's gastrointestinal tract, there has been concern about maternal use of VEGF inhibitors during nursing; however, it should be noted that infant formula (the usual alternative to breast milk) contains no VEGF.

See references