Concern	What to assess	Important difference
Embryo-fetal toxicity	Pregnancy exclusion; effective contraception	Pregnancy remains contraindicated despite removal of embryo-fetal REMS requirements
Hepatic injury	Aminotransferases; symptoms and bilirubin when indicated	Bosentan: baseline and monthly testing; schedules differ for other ERAs
Anemia	Hemoglobin before and during treatment as indicated	Timing is product-specific
Fluid retention	Weight, edema and HF symptoms	Can require treatment reassessment

FDA removed embryo-fetal toxicity REMS requirements in 2025. Bosentan’s hepatotoxicity REMS remains.