Aflibercept and Breastfeeding

Summary of use during lactation

This record refers to the use of intravitreal aflibercept. Aflibercept inhibits vascular endothelial growth factor (VEGF). Aflibercept is a large protein molecule with a molecular weight of 115,000 Daltons. Aflibercept appeared in breastmilk in small amounts in only one of four days after intravitreal injection in one mother. Absorption by the infant is unlikely because it is probably partly destroyed in the infant's gastrointestinal tract and poorly absorbed orally, so systemic effects in infants are not expected.[1] Aflibercept is approved for intravitreal injection in preterm infants with retinopathy of prematurity. The risk to nursing infants appears to be low. Since VEGF is present in human milk and is thought to help in maturation of the infant’s gastrointestinal tract, concern has been raised about the maternal use of VEGF inhibitors during breastfeeding.[2] However, the typical alternative to breastmilk is infant formula, which contains no VEGF. Some sources consider ranibizumab to be preferable to aflibercept in nursing mothers because of its lower systemic exposure after intravitreal injection.[3,4]

Drug levels in milk and infant serum

Maternal Levels. A woman with diabetic macular edema was given intravitreal aflibercept 2 mg one week postpartum. She was not breastfeeding her infant. Milk samples were obtained before the injection and on days 1 to 4 after the injection. Aflibercept was detected only on day 4 in a concentration of 10.9 mcg/L.[5] Infant Levels. Relevant published information was not found as of the revision date.

Effects in breastfed infants

Relevant published information was not found as of the revision date.

Effects on lactation and breastmilk

A woman with diabetic macular edema was given intravitreal aflibercept 2 mg one week postpartum. She was not breastfeeding her infant. Milk samples were obtained before the injection and on days 1 to 4 after the injection. VEGF levels were reduced from 10.6 mcg/L at baseline to 4.9 mcg/L on day 1, where it remained for the next 3 days.[5]

Alternative drugs to consider

(Intravitreal) Bevacizumab, Ranibizumab

References

1. Anderson PO. Monoclonal antibodies during breastfeeding. Breastfeed Med 2021;16:591–3.33956488 PubMed
2. Dalal PJ, Patel AL, Carle M, et al. Review of ophthalmic and breastfeeding medicine evidence: Real and theoretical risks of intravitreal anti-VEGF administration in lactating women. Retina 2020;40:2065–9.32796446 PubMed
3. Avery RL, Castellarin AA, Steinle NC, et al. Systemic pharmacokinetics and pharmacodynamics of intravitreal aflibercept, bevacizumab, and ranibizumab. Retina 2017;37:1847–58.28106709 PubMed
4. Banerjee M, Moharana S, Padhy SK. Systemic effects of intravitreal anti-VEGF therapy: A review of safety across organ systems. Ophthalmol Ther 202540478389 PubMed
5. Juncal VR, Paracha Q, Bamakrid M, et al. Ranibizumab and aflibercept levels in breast milk after intravitreal injection. Ophthalmology 2020;127:278–80.31526521 PubMed