Macitentan Tablets

Clinically significant adverse reactions that appear in other sections of the labeling include:

• Embryo-fetal Toxicity [see WARNINGS AND PRECAUTIONS]
• Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
• Fluid Retention [see WARNINGS AND PRECAUTIONS]
• Decrease in Hemoglobin [see WARNINGS AND PRECAUTIONS]

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Safety data for OPSUMIT were obtained primarily from one placebo-controlled clinical study in 742 patients with PAH (SERAPHIN study) [see Clinical Studies]. The exposure to OPSUMIT in this trial was up to 3.6 years with a median exposure of about 2 years (N=542 for 1 year; N=429 for 2 years; and N=98 for more than 3 years). The overall incidence of treatment discontinuations because of adverse events was similar across OPSUMIT 10 mg and placebo treatment groups (approximately 11%).

Table 2 presents adverse reactions more frequent on OPSUMIT than on placebo by ≥ 3%.

Table 2 : Adverse Reactions

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of OPSUMIT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune system disorders: hypersensitivity reactions (angioedema, pruritus and rash)

Respiratory, thoracic and mediastinal disorders: nasal congestion

Gastrointestinal disorders: Elevations of liver aminotransferases (ALT, AST) and liver injury have been reported with Opsumit use; in most cases alternative causes could be identified (heart failure, hepatic congestion, autoimmune hepatitis). Endothelin receptor antagonists have been associated with elevations of aminotransferases, hepatotoxicity, and cases of liver failure [see WARNINGS AND PRECAUTIONS].

General disorders and administration site conditions: edema/fluid retention. Cases of edema and fluid retention occurred within weeks of starting Opsumit, some requiring intervention with a diuretic, fluid management or hospitalization for decompensated heart failure [see WARNINGS AND PRECAUTIONS].

Cardiac disorders: symptomatic hypotension