Macitentan

1 INDICATIONS AND USAGE OPSUMIT is an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in adults to reduce the risks of disease progression and hospitalization for PAH ( 1.1 ). 1.1 Pulmonary Arterial Hypertension OPSUMIT is an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in adults to reduce the risks of disease progression and hospitalization for PAH. Effectiveness was established in a long-term study in PAH patients with predominantly WHO Functional Class II–III symptoms treated for an average of 2 years.

6 ADVERSE REACTIONS Clinically significant adverse reactions that appear in other sections of the labeling include: Embryo-fetal Toxicity [see Warnings and Precautions (5.1) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Fluid Retention [see Warnings and Precautions (5.3) ] Decrease in Hemoglobin [see Warnings and Precautions (5.4) ] Most common adverse reactions (more frequent than placebo by ≥3%) are anemia, nasopharyngitis/pharyngitis, bronchitis, headache, influenza, and urinary tract infection ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Actelion at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

8.1 Pregnancy Risk Summary Based on data from animal reproduction studies, OPSUMIT may cause embryo-fetal toxicity, including birth defects and fetal death, when administered to a pregnant female and is contraindicated during pregnancy. There are risks to the mother and the fetus associated with pulmonary arterial hypertension in pregnancy [see Clinical Considerations ] . Available data from postmarketing reports and published literature over decades of use with ERAs in the same class as OPSUMIT have not identified an increased risk of major birth defects; however, these data are limited.

WARNING: EMBRYO-FETAL TOXICITY OPSUMIT is contraindicated for use during pregnancy because it may cause fetal harm based on animal data [see Contraindications (4.1) , Warnings and Precautions (5.1) , Use in Specific Populations (8.1) ]. Therefore, for females of reproductive potential, exclude pregnancy before the start of treatment with OPSUMIT. 5 WARNINGS AND PRECAUTIONS ERAs cause hepatotoxicity and liver failure. Obtain baseline liver enzymes and monitor as clinically indicated ( 5.2 ). Fluid retention may require intervention ( 5.3 ). Decreases in hemoglobin ( 5.4 ). Pulmonary edema in patients with pulmonary veno-occlusive disease. If confirmed, discontinue treatment ( 5.5 ). Decreases in sperm count have been observed in patients taking ERAs ( 5.6 ). 5.1 Embryo-fetal Toxicity Based on data from animal reproduction studies, OPSUMIT may cause fetal harm when administered to a pregnant patient and is contraindicated during pregnancy. The available human data for ERAs do not establish the presence or absence of major birth defects related to the use of OPSUMIT. 4 CONTRAINDICATIONS Pregnancy ( 4.1 ) Hypersensitivity ( 4.2 ) 4.1 Pregnancy OPSUMIT may cause fetal harm when administered to a pregnant woman. OPSUMIT is contraindicated in females who are pregnant. OPSUMIT was consistently shown to have teratogenic effects when administered to animals.