Selexipag in the Treatment of Pulmonary Arterial Hypertension

Main Article Content

Phannita Wattanaruengchai

Abstract

The cornerstone of drugs used to slow the progressive disease of pulmonary hypertension exhibit through these three signaling pathways including activation through nitric oxide and prostacyclin pathway and inhibition through endothelin pathway. The effect of medications has been shown by promoting the vasodilatory, inhibiting platelet aggregation, reducing endothelial cell proliferation, reducing inflammation and in situ thrombosis. The decreased in pulmonary pressure results in improved right ventricular heart pumping. These outcomes lead to improvement in patient quality of life. Selexipag is a novel oral long-acting, selective prostacyclin receptor agonist. The drug and its active metabolite showed prominent in long acting and convenient for administration. Selexipag is used for monotherapy or combination in patients receiving endothelin receptor antagonists and/or phosphodiesterase type 5 inhibitors. The results from the clinical studies have showed that selexipag is associated with the decreased composite risk of death and complications, that driven by decreased risk of hospitalization due to progressive disease. Though, the common side effects include headache, diarrhea, nausea, and jaw-pain. The monitoring of long-term adverse drug events should be aware.

Downloads

Download data is not yet available.

Article Details

Section
Review Article

References

Asaki T, Kuwano K, Morrison K, Gatfield J, Hamamoto T, Clozel M. Selexipag: An oral and selective IP prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. J Med Chem. 2015;58(18):7128-37.

Barnett CF, Machado RF. Sildenafil in the treatment of pulmonary hypertension. Vasc Health Risk Manag. 2006;2(4):411-22.

Casserly B, Klinger JR. Ambrisentan for the treatment of pulmonary arterial hypertension. Drug Des Devel Ther. 2009;2:265-80.

Christman BW, McPherson CD, Newman JH, King GA, Bernard GR, Groves BM, et al. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med. 1992;327(2):70-5.

Dingemanse J, van Giersbergen PL. Clinical pharmacology of bosentan, a dual endothelin receptor antagonist. Clin Pharmacokinet. 2004;43(15):1089-115.

Dupuis J, Hoeper MM. Endothelin receptor antagonists in pulmonary arterial hypertension. Eur Respir J. 2008;31(2):407.

Food and Drug Administration Thailand. UPTRAVI [Internet]. 2018 [cited 2020 Jun 4]. Available from: http://pertento.fda.moph.go.th/FDA_SEARCH_DRUG/SEARCH_DRUG/pop-up_drug_ex.aspx?Newcode=U1DR1C1012611503911C.

Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37(1): 67-119.

Galiè N, Müller K, Scalise AV, Grünig E. PATENT PLUS: a blinded, randomised and extension study of riociguat plus sildenafil in pulmonary arterial hypertension. Eur Respir J. 2015;45(5):1314-22.

Gnerre C, Segrestaa J, Seeland S, Äänismaa P, Pfeifer T, Delahaye S, et al. The metabolism and drug-drug interaction potential of the selective prostacyclin receptor agonist selexipag. Xenobiotica. 2018;48(7):704-19.

Henrie AM, Nawarskas JJ, Anderson JR. Clinical utility of tadalafil in the treatment of pulmonary arterial hypertension: an evidence-based review. Core Evid. 2015;10:99-109.

Hoeper MM, Bogaard HJ, Condliffe R, Frantz R, Khanna D, Kurzyna M, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D42-50.

Khadka A, Singh Brashier DB, Tejus A, Sharma AK. Macitentan: An important addition to the treatment of pulmonary arterial hypertension. J Pharmacol Pharmacother. 2015;6(1):53-7.

Khaybullina D, Patel A, Zerilli T. Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. P&T. 2014;39(11):749-58.

Lan NSH, Massam BD, Kulkarni SS, Lang CC. Pulmonary arterial hypertension: Pathophysiology and treatment. Diseases. 2018;6(2):38.

Lindegaard Pedersen M, Krüger M, Grimm D, Infanger M, Wehland M. The prostacyclin analogue treprostinil in the treatment of pulmonary arterial hypertension. Basic Clin Pharmacol Toxicol. 2019.

Melian EB, Goa KL. Beraprost: a review of its pharmacology and therapeutic efficacy in the treatment of peripheral arterial disease and pulmonary arterial hypertension. Drugs. 2002;62(1):107-33.

Olschewski H. Inhaled iloprost for the treatment of pulmonary hypertension. Eur Respir Rev. 2009;18(111):29-34.

Prior DL, Adams H, Williams TJ. Update on pharmacotherapy for pulmonary hypertension. Med J Aust. 2016;205(6):271-6.

Simonneau G, Torbicki A, Hoeper MM, Delcroix M, Karlócai K, Galiè N, et al. Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. Eur Respir J. 2012;40(4):874-80.

Sitbon O, Channick R, Chin KM, Frey A, Gaine S, Galiè N, et al. Selexipag for the treatment of pulmonary arterial hypertension. N Engl J Med. 2015;373(26):2522-33.

Sitbon O, Vonk Noordegraaf A. Epoprostenol and pulmonary arterial hypertension: 20 years of clinical experience. Eur Respir Rev. 2017;26(143).

Tabima DM, Frizzell S, Gladwin MT. Reactive oxygen and nitrogen species in pulmonary hypertension. Free Radic Biol Med. 2012;52(9):1970-86.

U.S. Food and Drug Administration. Novel drug approvals for 2015 [Internet]. 2015 [cited 2020 Jun 4]. Available from: https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2015.

U.S. Food and Drug Administration. UPTRAVI [Internet]. 2017 [cited 2020 Jun 4]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207947s005lbl.pdf.

Waxman A. A review of sitaxsentan sodium in patients with pulmonary arterial hypertension. Vasc Health Risk Manag. 2007;3:151-7.