Macitentan Disease Interactions

Endothelin receptor antagonists (ERAs) have been associated with aminotransferase elevations, hepatotoxicity, and cases of liver failure. Hepatic function should be assessed before treatment initiation and closely monitored during treatment. Therapy should be discontinued if aminotransferase elevations are accompanied by increases in bilirubin, or clinical symptoms of hepatotoxicity such as nausea, vomiting, fever, abdominal pain or jaundice. Treatment should be avoided in patients with elevated aminotransferases at baseline as monitoring for hepatotoxicity may be more difficult. In general, the use of ERAs is not recommended for patients with moderate to severe hepatic impairment.

Clinical studies have shown that most endothelin receptor antagonists decrease hemoglobin concentration and hematocrit levels. There are some postmarketing reports of anemia cases which needed blood transfusion. Hemoglobin and hematocrit levels should be measured prior to treatment initiation and should be monitored periodically thereafter. Initiation of therapy is not recommended in patients with clinically significant anemia.

Peripheral edema and fluid retention are known clinical consequences of pulmonary hypertension and also known effects of endothelin receptor antagonists. Caution and monitoring is recommended if these agents are used in patients with underlying left ventricular dysfunction or underlying heart failure, as they have an increased risk for developing significant fluid retention that may need treatment or require discontinuation.