On 22nd November 2012 Actelion announced that it had successfully submitted the Market Authorisation Application to the European Medicines Agency (EMA) and a validation letter had been received. A decrease in hemoglobin to below 10.0 g/dL was reported in 8.7% of the OPSUMIT group vs 3.4% for placebo. ", NOTES TO THE EDITORORAL PRESENTATION AT ERS Congress 2013, Effect of macitentan on morbidity and mortality in pulmonary arterial hypertension: a randomised controlled trial, H-A Ghofrani, R Channick, M Delcroix, N Galiè, P Jansa, F-O Le Brun, S Mehta, C Mittelholzer, T Pulido, BKS Sastry, O Sitbon, R Souza, O Sitbon, A Torbicki,L Rubin, G SimmoneauOral presentation: September 09, 10.00-10.15 Abstract reference: TBC. Actelion is continuing to work with regulatory authorities worldwide to bring this important medicine to patients. Global enrollment was completed in December 2009 with a total of 742 patients. Roland Haefeli Senior Vice President, Head of Investor Relations & Public Affairs Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH-4123 Allschwil +41 61 565 62 62 +1 650 624 69 36 www.actelion.com. Male patients are not enrolled in the REMS. Macitentan and Morbidity and Mortality in Pulmonary Arterial Hypertension.

Chest 2012;142:448-56. Should signs of pulmonary edema occur, consider the possibility of associated PVOD. This form is NOT intended for medical information requests or for reporting information about any medication side effects. The hazard ratio for macitentan 3 mg versus placebo was 0.70 (97.5% CI, 0.52 to 0.96; p=0.0108) and the hazard ratio for macitentan 10 mg versus placebo was 0.55 (97.5% CI, 0.39 to 0.76; p<0.0001). Decreases in hemoglobin seldom require transfusion.

ERAs have caused elevations of aminotransferases, hepatotoxicity, and liver failure. The clinical pharmacology program also indicated a low propensity of macitentan for drug-drug interactions [6,7,8] . Prescribers must be certified with the program by enrolling and completing training. J PharmacolExpTher. doi:10.1371/journal.pone.0047662. Please click here for full Prescribing Information, including BOXED WARNING. 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. 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. This effect was observed irrespective of whether or not patients were already treated with other therapies for PAH. Improved Long-Term Clinical Outcomes Regardless of Time of Treatment Initiation, and The AC-055-302/SERAPHIN study will be an event-driven Phase III study, comparing two different doses of macitentan (ACT-064992) (3 and 10 mg) vs placebo in patients with symptomatic PAH. Effect of cyclosporine A and rifampin on the pharmacokinetics of macitentan, a tissue-targeting dual endothelin receptor antagonist.

Xenobiotica. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist. Macitentan has a number of potentially key beneficial characteristics including increased in vivo preclinical efficacy versus existing ERAs resulting from sustained receptor binding [4] and physicochemical properties that allow enhanced tissue penetration [5]. ABOUT OPSUMIT® (MACITENTAN)SUBMISSIONS TO HEALTHCARE AUTHORITIES. Use other PAH treatment options when strong CYP3A4 inhibitors are needed as part of HIV treatment. Professor Ghofrani commented on the findings shared at ERS; "As the first event-driven, outcomes trial in PAH, the findings of the SERAPHIN study have been keenly anticipated.



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