Two drugs used to treat retinal diseases are excreted into breast milk, which could cause health concerns for infants, a study in Ophthalmology reports.
Canadian researchers used a trio of different patient scenarios of intravitreal anti-VEGF therapy in lactating women and investigated whether ranibizumab or aflibercept reached the breast milk in each of them.
Three patients were enrolled in the study, and breast milk was collected at baseline (one hour before injection), every day for the first week after injection and then 14, 21 and 28 days after injection in the first two patients.
Patient one was a 37-year-old woman nursing a 16-month-old child and who was diagnosed with myopic choroidal neovascularization, for which ranibizumab was recommended. Breastfeeding was discontinued before injection, and no breast milk was pumped outside of study visits.
The second patient was a 37-year-old woman diagnosed with myopic choroidal neovascularization who was nursing a one-month-old child. She had received one 0.5mg intravitreal ranibizumab injection four weeks before baseline. She continued receiving ranibizumab therapy and breastfed regularly throughout treatment.
The third patient, a 24-year-old woman diagnosed with diabetic macular edema, gave birth to a child one week before baseline and decided not to breastfeed. She began treatment with 2.0mg intravitreal aflibercept. Breast milk was collected at baseline (one hour before injection) and on days one through four, after which samples could not be obtained because of the lack of additional breast milk production. No breast milk was pumped, nor did breastfeeding take place outside of study visits, the researchers noted.
In the first patient, ranibizumab was detected starting on day three (34.7ng/ ml), with generally increasing levels over time. The researchers found VEGF-A reduced from 22.8ng/ml at baseline to 12.3ng/ml on day one and down to 4.9ng/ml on day 28.
However, in the second patient—who was breastfeeding continuously— ranibizumab levels remained below the lower limit of quantitation throughout all study time points, and VEGF-A concentrations remained mostly unchanged.
The study detected aflibercept on day four (10.9ng/ml) in the third patient, whereas VEGF-A levels were reduced from 10.6ng/ml at baseline to 4.9ng/ml on day one.
Based on the results found in patients one and three, both ranibizumab and aflibercept reached the breast milk with a corresponding reduction in VEGF-A levels after intravitreal injection, the researchers noted.
“Because aflibercept was detected only on day four and ranibizumab starting on day three, whereas VEGF-A levels were reduced on day one, we hypothesize that both drugs likely reached the breast milk by day one and initially bound with free VEGF present in the breast milk,” the researchers wrote in their paper. “Because our assays detect only free drug, free ranibizumab and aflibercept levels could have remained at below the [lower limit of quantitation] during the first days after injection.”
Ranibizumab detection was influenced by whether the patient was breastfeeding continuously, they added.
These findings are important when counseling nursing women who require anti-VEGF therapy because they raise a possible safety concern for the developing infant, the investigators said.
The labels for both ranibizumab and aflibercept warn that it is unknown whether these drugs are excreted in human breast milk and, as a precaution, breastfeeding has traditionally not been recommended while using these drugs. However, each patient must be treated individually, taking into consideration the importance of the drug to the mother, the researchers said.
Human breast milk contains VEGF produced by the lactiferous mammary gland cells, which has an important function in the development and maturation of the infant’s digestive system. Therefore, anti-VEGF therapy in a nursing mother raises a concern about possible adverse events in the infant in the event that these drugs pass into the breast milk and suppress local VEGF levels, the investigators explained.
|Juncal VR, Paracha Q, Bamakrid M, et al. Ranibizumab and aflibercept levels in breast milk after intravitreal injection. Ophthalmology. September 12, 2019. [Epub ahead of print].|