Pregnancy Outcomes Following Macitentan or Bosentan Exposure Before or During Pregnancy: Review of Cases Reported to the Manufacturer's Global Safety Database
Karen M. Olsson, Maria Solonets, Yan Yu, Anna Neild, Cécile Valette, Anna R. Hemnes
https://doi.org/10.1002/pul2.70286
Abstract
Pregnancy in pulmonary arterial hypertension (PAH) is associated with substantial risks. Endothelin receptor antagonists (ERAs), including macitentan and bosentan, are contraindicated in pregnancy due to teratogenic effects observed in animal studies. Medication guides/patient cards inform patients about the risk of serious birth defects and safe-use conditions for ERAs. In April 2025, pregnancy-related Risk Evaluation and Mitigation Strategies for both treatments were removed in the US. Due to the contraindications in place, published data on ERAs in human pregnancy remain sparse. Here, we summarize cases of exposure to macitentan or bosentan during pregnancy reported to the drug manufacturer. Over the last 10 years, the estimated pregnancy reporting incidence rate among women of reproductive potential was < 1.0% (person-years) for macitentan and < 0.5% (person-years) for bosentan. The results below are based on the number of individuals with data available for each event of interest. Exposure was most frequently reported during the first trimester (n = 96/106 for macitentan and n = 203/229 for bosentan). Where reported, outcomes for pregnancies included elective termination (n = 61/124 for macitentan and n = 94/215 for bosentan), live birth (n = 40/124; n = 78/215), and spontaneous abortion/stillbirth (n = 21/124; n = 38/215). Treatment was discontinued following detection of pregnancy in 117/144 and 141/231 cases, respectively. Of 40 and 78 live births, respectively, 24 and 50 neonates were born prematurely, 21 and 47 were healthy, and two and five had congenital anomalies. There was no consistent pattern of malformations involving the cardiovascular system, head or face as observed in nonclinical studies. These findings represent the current experience with ERA exposure during pregnancy.
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