Pagenax Use In Pregnancy & Lactation

Pregnancy: Risk summary: There are no adequate and well-controlled studies of Pagenax administration in pregnant women and no animal reproduction studies have been conducted. The potential risk of use of Pagenax in pregnancy is unknown. A study in pregnant cynomolgus monkeys did not indicate any harmful effects with the respect to pre- or postnatal development at approximately 6-times the human exposure based on serum C_max (see Animal data as follows). However, based on the anti-VEGF mechanism of action, brolucizumab must be regarded as potentially teratogenic and embryo/fetotoxic. Therefore, Pagenax should not be used during pregnancy unless the expected benefits outweigh the potential risks to the fetus.
Animal data: No reproductive or fertility studies have been conducted. In an enhanced pre- and postnatal development (ePPND) study in pregnant cynomolgus monkeys, brolucizumab was administered to all animals by intravitreal (IVT) injection to one eye at doses of 3 or 6 mg once every 4 weeks until delivery. One additional injection was administered to a subset of animals 28 days post-partum and had a milk collected for tocixokinetic evaluations. There was no impact of IVT administration of brolucizumab on embryo-fetal development, pregnancy or parturitition; or on the survival, growth, or postnatal development of offspring. This represents an exposure approximately 6-times the human exposure (based on serum Cmax) at the proposed clinical dose of 6 mg. However, VEGF inhibition has been shown to affect follicular development, corpus luteum function, and fertility. Based on the mechanism of action of VEGF inhibitors, there is a potential risk to female reproduction and to embryo-fetal development.
Lactation: It is unknown if brolucizumab is transferred into human milk after administration of Pagenax. There are no data on the effects of Pagenax on the breastfed child or on milk production. In an ePPND study, brolucizumab was not detected in the maternal milk or infant serum of cynomolgus monkeys. Because of the potential for adverse drug reactions in the breastfed child, breastfeeding is not recommended during treatment and for at least one month after the last dose when stopping treatment with Pagenax.
Females of reproductive potential: Females of reproductive potential should use effective contraception (methods that result in less than 1 % pregnancy rates) during treatment with Pagenax and for at least one month after the last dose when stopping treatment with Pagenax.