CardioSource WorldNews December 2014 - Page 61

Patient dramatization when hepatic enzyme levels normalize in patients who have not experienced clinical symptoms of hepatotoxicity. Hemoglobin Decrease Decreases in hemoglobin concentration and hematocrit have occurred following administration of other ERAs and in clinical studies with OPSUMIT. These decreases occurred early and stabilized thereafter. In the SERAPHIN study, OPSUMIT caused a mean decrease in hemoglobin (from baseline to 18 months) of about 1.0 g/dL vs no change in the placebo group. A decrease in hemoglobin to below 10.0 g/dL was reported in 8.7% of the OPSUMIT group vs 3.4% for placebo. Decreases in hemoglobin seldom require transfusion. Initiation of OPSUMIT is not recommended in patients with severe anemia. Measure hemoglobin prior to initiation of treatment and repeat during treatment as clinically indicated. Pulmonary Edema with Pulmonary Veno-occlusive Disease (PVOD) Should signs of pulmonary edema occur, consider the possibility of associated PVOD. If confirmed, discontinue OPSUMIT. ADVERSE REACTIONS Most common adverse reactions (more frequent than placebo by ≥3%) were anemia (13% vs 3%), nasopharyngitis/pharyngitis (20% vs 13%), bronchitis (12% vs 6%), headache (14% vs 9%), influenza (6% vs 2%), and urinary tract infection (9% vs 6%). DRUG INTERACTIONS Strong inducers of CYP3A4 such as rifampin significantly reduce macitentan exposure. Concomitant use of OPSUMIT with strong CYP3A4 inducers should be avoided. Strong inhibitors of CYP3A4 like ketoconazole approximately double macitentan exposure. Many HIV drugs like ritonavir are strong inhibitors of CYP3A4. Avoid concomitant use of OPSUMIT with strong CYP3A4 inhibitors. Use other PAH treatment options when strong CYP3A4 inhibitors are needed as part of HIV treatment. Please see Brief Summary of Prescribing Information, including BOXED WARNING for embryo-fetal toxicity, on adjacent pages. Decreased Sperm Counts Other ERAs have caused adverse effects on spermatogenesis. Counsel men about potential effects on fertility. ® OPSUMIT is a registered trademark of Actelion Pharmaceuticals, Ltd. © 2014 Actelion Pharmaceuticals US, Inc. All rights reserved. MAC-00323 0114 www.OpsumitHCP.com