Sybrava Use In Pregnancy & Lactation

Pregnancy: Risk summary: There are no available data on the use of inclisiran (Sybrava) in pregnant women to inform a drug-associated risk. Animal reproduction studies in rats and rabbits have not shown risk of increased fetal abnormalities with subcutaneous administration of inclisiran during organogenesis at doses equivalent to 16- to 39-fold the maximum recommended human dose (MRHD) based on AUC (see Animal data as follows).
Animal data: In embryo-fetal development studies conducted in pregnant female Sprague-Dawley rats and New Zealand White rabbits, inclisiran was administered by subcutaneous injection at 50, 100 and 150 mg/kg once daily during the period of organogenesis (rats: Days 6 to 17 post coitum; rabbits: Days 7 to 19 post coitum). There was no evidence of embryo-fetal death, fetotoxicity or teratogenicity. The highest doses tested were associated with safety margins in rats and rabbits of 16.0-fold and 39.3-fold, respectively, based on AUC, compared to exposures observed at the MRHD.
In rats, inclisiran was detected in fetal plasma; the concentrations generally increased with increasing dose, but were markedly (65- to 154-fold) lower compared to maternal levels. There was no inclisiran detected in fetal livers in any dose group. In rabbits, inclisiran was below the lower limit of quantitation in fetal plasma as well as liver.
In the pre- and postnatal development study conducted in pregnant female Sprague-Dawley rats, inclisiran was administered once daily by subcutaneous injection at 50, 100 and 150 mg/kg from Day 6 post coitum to lactation Day 20. Inclisiran was well-tolerated with no evidence of maternal toxicity and no effects on maternal performance. There were no adverse effects on the offspring.
Lactation: Risk Summary: It is not known if inclisiran is transferred into human milk after administration of inclisiran. There are no data on the effects of inclisiran on the breastfed child or on milk production. Inclisiran was present in rat milk following once-daily subcutaneous injection. However, there is no evidence of systemic absorption in suckling rat neonates. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for inclisiran and any potential adverse effects on the breastfed child from inclisiran.
Females and males of reproductive potential: Infertility: There are no data on the effect of inclisiran on human fertility. No effects on fertility were observed in female and male rats at doses equivalent to 20.4-fold and 44.1-fold based on AUC, compared to exposures observed at the MRHD (see Pharmacology: Toxicology: Non-Clinical Safety Data under Actions).