scholarly journals Macitentan and Tadalafil (Opsynvi)

2022 ◽  
Vol 2 (1) ◽  
Author(s):  
Reimbursement Team

CADTH recommends that Opsynvi should be reimbursed by public drug plans for the long-term treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to reduce morbidity in patients in WHO functional class (FC) II or III whose PAH is idiopathic, heritable, or associated with connective tissue disease or congenital heart disease if certain conditions are met. Opsynvi should only be covered for patients who are currently treated simultaneously with stable doses of macitentan 10 mg and tadalafil 40 mg as separate tablets. Opsynvi should only be reimbursed if prescribed by a specialist with expertise in managing and treating patients with PAH and if the price of Opsynvi is negotiated to ensure cost savings in comparison with separate macitentan and tadalafil tablets.

2016 ◽  
Vol 311 (4) ◽  
pp. R721-R726 ◽  
Author(s):  
Martine Clozel

Endothelin receptor antagonists (ERAs) are used for the treatment of pulmonary arterial hypertension (PAH). Macitentan, a dual (ETA+ETB) ERA approved for the long-term treatment of PAH, was discovered through a tailored research program aimed at improving efficacy and safety over the existing ERAs. The goal of improved efficacy was based on the understanding that not only the ETA receptor but also the ETB receptor contributed to the hemodynamic and structural changes induced by endothelin-1 (ET-1) in pathological conditions and on the predefined requirements for optimal tissue penetration and binding kinetics of the antagonist. The goal of improved safety was based on the discovery of the role of ETB receptors in vascular permeability and vasopressin release and on the elucidation of the mechanism by which bosentan (the first approved oral dual ETA/ETB ERA) caused liver enzyme changes. Our intention was to design a molecule that would block ETA and ETB receptors optimally and would not interfere with bile salt elimination. This review takes us through the drug discovery journey that led to the discovery, development, and registration of macitentan.


Circulation ◽  
2003 ◽  
Vol 108 (17) ◽  
pp. 2066-2069 ◽  
Author(s):  
Evangelos D. Michelakis ◽  
Wayne Tymchak ◽  
Michelle Noga ◽  
Linda Webster ◽  
Xi-Chen Wu ◽  
...  

CHEST Journal ◽  
2003 ◽  
Vol 123 (4) ◽  
pp. 1293-1295 ◽  
Author(s):  
Leopold Stiebellehner ◽  
Ventzislav Petkov ◽  
Karin Vonbank ◽  
Georg Funk ◽  
Peter Schenk ◽  
...  

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hans Klose ◽  
Kelly M. Chin ◽  
Ralf Ewert ◽  
Henning Gall ◽  
Joseph Parambil ◽  
...  

Abstract Background The oral IP receptor agonist selexipag is approved for the long-term treatment of pulmonary arterial hypertension (PAH). Treatment interruptions should be avoided due to the progressive nature of the disease. An intravenous (IV) formulation of selexipag was developed to provide a treatment option for short-term interruptions to oral selexipag. In this prospective, multicenter, open-label study, the safety, tolerability, and pharmacokinetics of temporarily switching between oral and IV selexipag were investigated (NCT03187678, ClinicalTrials.gov). Methods PAH patients receiving stable oral selexipag doses were enrolled. Following three consecutive IV selexipag infusions patients resumed oral selexipag. Corresponding IV and oral doses were selected to achieve comparable exposure to the active metabolite of selexipag. Safety outcomes were monitored throughout, and pharmacokinetic samples were obtained after oral and IV administration. Results All 20 patients completed the study. Fifteen patients had adverse events (AEs), most were mild, and none resulted in discontinuation. Headache was the most common AE throughout the study (four patients). Three serious AEs occurred in two patients with underlying comorbidities when oral dosing had resumed. There were no changes in WHO functional class for any patient and no clinically symptomatic changes in blood pressure were observed. Comparable exposure to the active metabolite of selexipag was demonstrated following corresponding oral and IV selexipag doses. Conclusions Temporarily switching between corresponding doses of oral and IV selexipag was well-tolerated with no unexpected safety findings and comparable exposure to the active metabolite. Treatment with IV selexipag is a feasible option to bridge temporary oral selexipag treatment interruptions.


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