Drugs, Pregnancy & Lactation

The FDA’s novel drugs approved in 2017


 


Semaglutide (Ozempic) (MW 4,114), given subcutaneously, is a glucagon-like peptide indicated to improve glycemic control in type 2 diabetes mellitus. In rats given the drug during organogenesis, embryo-fetal death, structural defects, and alterations in growth were observed. In rabbits and monkeys given the drug during organogenesis, there were early pregnancy losses and structural abnormalities. In addition, there was marked maternal body weight loss in both animal species. Vestronidase alfa-vjbk (Mepsevii) is given intravenously. It is indicated for the treatment of Mucopolysaccharidosis VII (Sly syndrome). The calculated average MW of each nonglycosylated peptide chain is 72,562. In rats and rabbits given the drug during organogenesis, there was no maternal toxicity or adverse developmental outcomes.

Gastrointestinal

Plecanatide (Trulance) (MW 1,682) is an oral drug indicated for the treatment of constipation. The drug and its active metabolite are negligibly absorbed systemically and fetal exposure to the drug is not expected. In mice and rabbits given the oral drug during organogenesis, no effects on embryo-fetal development were observed. Telotristat ethyl (Xermelo) (MW 754) is an oral drug indicated for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analog (MW not specified) therapy in adults not controlled by somatostatin analog. When given during organogenesis in rats, there was no effect on embryo-fetal development at doses that were about nine times the recommended human dose. However, an increased incidence of mortality in rat offspring was observed when the drug was given from organogenesis through lactation. During organogenesis in rabbits, the drug had no embryo-fetal effects at doses that were 10 or more times the human dose.

Hematologics

Betrixaban (Bevyxxa) (MW 568) is an oral factor Xa inhibitor indicated for the prophylaxis of venous thromboembolism. The drug was not associated with adverse developmental fetal outcomes in rats and rabbits. However, maternal hemorrhage did occur. In humans, there is an increased risk of hemorrhage during pregnancy and delivery. Emicizumab (Hemlibra) (MW 145,600), given subcutaneously, is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding in patients with hemophilia A with factor VIII inhibitors. Animal reproduction studies have not been conducted. It is a human monoclonal IgG antibody and, though the MW is high, IgG antibodies are known to cross the placenta.


Immunologic

Sarilumab (Kevzara) (MW 150,000) is given subcutaneously. It is indicated for patients with moderate to severe rheumatoid arthritis. Reproduction studies were conducted in pregnant monkeys. There was no evidence of embryo toxicity or fetal malformations. Based on this data, the human pregnancy risk is low.

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