Is intravitreal Bevacizumab (Avastin) injection safe in a breastfeeding patient?

From the Guidelines

Intravitreal Bevacizumab (Avastin) injections are generally considered safe during breastfeeding, and breastfeeding can be continued without interruption after receiving this treatment. The systemic absorption of bevacizumab following intravitreal injection is minimal, with extremely low levels entering the bloodstream and even less likely to pass into breast milk in significant amounts 1. The large molecular size of bevacizumab (149 kDa) further limits its transfer into breast milk, and any small amount that might transfer would likely be destroyed in the infant's gastrointestinal tract rather than absorbed.

Key Considerations

• No specific waiting period or pumping and discarding milk is necessary after the procedure.
• Patients should be informed that while there are limited specific studies on bevacizumab in breastfeeding, the theoretical risk to the infant is extremely low based on the pharmacological properties of the medication and its administration route.
• The benefits of treating the mother's eye condition typically outweigh any theoretical risk to the breastfed infant.
• Patients should continue their normal breastfeeding routine while receiving necessary eye treatment, as the use of compatible medications during breastfeeding is encouraged to maintain disease control 1.

Breastfeeding Recommendations

• The American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases suggests that breastfeeding can be continued with compatible medications, and individualized risks and benefits should be reviewed with each patient 1.
• Many medications may be initiated or continued during lactation, and the relative infant dose is considered safe if it is less than 10% of the maternal dose.
• Although bevacizumab is not explicitly mentioned in the guideline, its pharmacological properties suggest a low risk of transfer into breast milk, making it likely compatible with breastfeeding.

From the FDA Drug Label

Lactation: Advise women not to breastfeed during treatment with Avzivi and for 6 months after the last dose [see Use in Specific Populations ( 8.2)] The intravitreal Bevacizumab (Avastin) injection is not recommended for use in breastfeeding patients, as the drug label advises women not to breastfeed during treatment and for 6 months after the last dose 2.

From the Research

Safety of Intravitreal Bevacizumab in Breastfeeding Patients

• The safety of intravitreal Bevacizumab (Avastin) injection in breastfeeding patients is a concern due to the potential risk of the drug being transferred to the infant through breast milk 3.
• Studies have shown that Bevacizumab has a low serum concentration after intravitreal injection, but its effects on plasma-free VEGF concentrations and breastmilk VEGF levels are still unclear 3.
• A review of the literature suggests that ranibizumab, another anti-VEGF agent, has a lower serum concentration and less effect on maternal serum and breastmilk VEGF levels compared to Bevacizumab and aflibercept 3.
• However, there is limited research on the systemic effects of intravitreal Bevacizumab, and further investigation is needed to determine its safety in breastfeeding patients 4.
• A case series and systematic review of the literature found that intravitreal anti-VEGF injections, including Bevacizumab, may not necessarily compromise obstetric outcomes, but clear associations cannot be drawn due to small numbers and confounders 5.

Pharmacology and Systemic Effects

• Bevacizumab has an Fc domain that subjects it to FcRn recycling, extending its half-life compared to ranibizumab, which lacks the Fc domain 3.
• The systemic absorption of Bevacizumab after intravitreal injection can cause systemic effects, such as hematuria, as reported in a case study 4.
• The use of intravitreal Bevacizumab has been growing due to its easy availability and low cost, despite safety concerns and the fact that it is still an unlicensed drug for intraocular use 6.

Clinical Considerations

• When considering intravitreal Bevacizumab treatment for breastfeeding patients, clinicians should weigh the benefits of vision-saving treatment against the potential risks to the infant 5, 3.
• Factors to consider in medical decision-making include the gestational and post-natal age of the child and whether it is feasible to avoid breastfeeding for the half-life duration of the intravitreal agent rather than ceasing breastfeeding altogether 3.