Abevmy Use In Pregnancy & Lactation

Pregnancy: Female patients of reproductive potential should be advised to use effective contraception during treatment with bevacizumab and for 6 months following the last dose of bevacizumab.
Summary of Risks: Based on findings in animals and the drug's mechanism of action, bevacizumab may cause harm to the foetus [see Section Mechanism of Action]. A limited number of cases of foetal malformations have been observed in women treated with bevacizumab (Reference Product) alone or in combination with known embryotoxic chemotherapeutics. These reports are however insufficient to determine bevacizumab-associated risks. In pregnant rabbits, intravenous administration of bevacizumab (Reference Product) every 3 days during organogenesis (doses were approximately 1 to 10 times the clinical dose of 10 mg/kg) caused foetal resorptions, decreased maternal and foetal weight gain and multiple congenital malformations; which included corneal opacities and abnormal ossification of the skull and skeleton (including limb and phalangeal defects). Animal models also link angiogenesis and VEGF and VEGF Receptor 2 (VEGFR2) to critical aspects of female reproduction, embryo foetal development, and postnatal development. Pregnant women should be advised of the potential risk to a foetus.
Summary of Animal Data: Decreases in maternal and foetal body weights and increased foetal resorptions were observed in pregnant rabbits given 10 to 100 mg/kg bevacizumab (Reference Product) [approximately 1 to 10 times the clinical dose, 10 mg/kg] every three days during organogenesis (gestation days 6-18). The number of litters containing foetuses with any type of malformation increased in relation to dose (42.1% for the 0 mg/kg dose, 76.5% for the 30 mg/kg dose, and 95% for the 100 mg/kg dose); as did the number of litters containing foetuses with foetal alterations (9.1% for the 0 mg/kg dose, 14.8% for the 30 mg/ kg dose, and 61.2% for the 100 mg/kg dose). All dose levels showed skeletal deformities. Some abnormalities including meningocele were seen only at the 100 mg/kg dose level. Reduced or irregular ossification in the skull, jaw, spine, ribs, tibia and bones of the paws; fontanel, rib and hindlimb deformities; corneal opacity; and absent hindlimb phalanges, were some of the teratogenic effects observed.
Lactation: There is no data to indicate whether bevacizumab is present in human milk; has effects on the breast fed infant; or effects on milk production. The literature suggests that antibodies in breast milk do not enter the neonatal and infant circulation in substantial amounts; though human IgG is present in human milk. Nursing women should be advised that breastfeeding is not recommended during treatment with bevacizumab, because of the potential for serious adverse reactions in breastfed infants. Nursing women should not breast-feed for at least six months following the last dose of bevacizumab.
Females of Reproductive Potential: Contraception: Harm to the foetus may result if bevacizumab is administered to a pregnant woman. Female patients of reproductive potential should be advised to use effective contraception during treatment with bevacizumab and for 6 months following the last dose of bevacizumab (see Pregnancy as previously mentioned).
Infertility: The risk of ovarian failure increases with bevacizumab, and fertility may be impaired. Prior to starting treatment with bevacizumab, female patients of reproductive potential must be informed of the risk of ovarian failure. The long term effects on fertility are unknown. In some patients, ovarian function recovered after bevacizumab (Reference Product) treatment was discontinued (see Precautions and Adverse Reactions).