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The Patient with Non-Group 2 Pulmonary Hypertension
Published in Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler, Heart Failure, 2023
Sophia Anastasia Mouratoglou, George Giannakoulas
Selexipag is a selective prostacyclin IP receptor agonist available for oral administration at a starting dose of 200 μg twice daily, gradually up-titrated to the target dose of 1600 μg twice daily. The most common side effects are similar to those seen by other prostanoids. Selexipag reduced the composite of death, hospitalization for PAH worsening, disease progression, and listing for transplantation in a large, event-driven, randomized, trial, in which 80% of patients were on background oral PAH advanced treatment.76,77
Pulmonary Hypertension in Pregnancy
Published in Afshan B. Hameed, Diana S. Wolfe, Cardio-Obstetrics, 2020
Prostanoids have no known teratogenic effects and are often utilized in pregnant patients with pulmonary hypertension. They are potent pulmonary vasodilators, and may also enhance right ventricular function [17]. They are available in parenteral or inhaled formulations. Currently available parenteral prostaglandins include epoprostenol, treprostinil, and iloprost [17]. Selexipag is a selective prostacyclin receptor agonist that is available in an oral formulation. It has recently been approved in the United States for treatment of PAH and has been shown to decrease pulmonary vascular resistance and improve morbidity [3]. Pre-pregnancy use of these medications may be an indicator of more severe disease [17].
Pulmonary hypertension: Hemodynamic assessment and response to vasodilators
Published in Debabrata Mukherjee, Eric R. Bates, Marco Roffi, Richard A. Lange, David J. Moliterno, Nadia M. Whitehead, Cardiovascular Catheterization and Intervention, 2017
Myung H. Park, Vallerie V. Mclaughlin
Selexipag is an oral prostacyclin IP receptor agonist, which as a diphenylpyrazine moiety, is chemically distinct from prostacyclin and prostanoid analogues. Selexipag becomes hydrolyzed via enzymatic actions to a long-acting active metabolite that has a half-life of about 8 hours. Distinct from other prostanoid analogues, it has been shown to be highly selective for the human prostacyclin IP receptor. In the Prostacyclin (PGI2) Receptor Agonist in Pulmonary Arterial Hypertension (GRIPHON) trial, the primary end- point of morbidity and mortality occurred in 27% of selexi- pag-treated patients and 41.6% of patients receiving placebo (hazard ratio 0.6; P < 0.001), mostly driven by a decrease in morbidity. There was no significant effect on 6MWD. Adverse effects were consistent with that of prostacyclins, namely headache, jaw pain, diarrhea, and nausea.
Real-world practice patterns and characteristics of adverse events with selexipag in Korean patients with pulmonary arterial hypertension
Published in Expert Opinion on Drug Safety, 2022
Sung-A Chang, Sang Hyun Lee, Jung Hyun Choi, Wook-Jin Chung, Jae Young Choi, Hyung-Kwan Kim, Hae-Ok Jung, Seong-Mi Park, Won-Jang Kim, Su Young Jung, Hyuk-Jae Chang
This observational study has some limitations. The observation period after administration of selexipag was relatively short (approximately 24 weeks) and not sufficient to evaluate mortality and morbidity in the long term. Furthermore, there may be a degree of collection bias in the safety data because they were collected from entries made in the electronic medical records during visits, and the majority were collected retrospectively [22]. A combination of retrospective and prospective registration methods enables to have a sufficient sample size to analysis safety data, but that combined way may be subject to confounding that can influence the quality of collecting variables. Because the blinding is not performed in this observational study, there may be also potential bias derived from investigators who determined the treatment of the patients and were informed that their records would be used in the analysis. Given that this was not a controlled study and majority of patients were registered retrospectively, collection of clinical outcomes data was not mandatory, so only limited amount of these data were available for analysis. Nevertheless, observational studies conducted in actual clinical practice have the advantage of providing clinicians and patients with real evidence regarding treatment of PAH with selexipag. This information will lead to a better understanding of safety concerns, trends in occurrence of AEs, and the gap between the characteristics of a controlled narrowly defined study population and those of a real-world population.
The metabolism and drug–drug interaction potential of the selective prostacyclin receptor agonist selexipag
Published in Xenobiotica, 2018
Carmela Gnerre, Jérôme Segrestaa, Swen Seeland, Päivi Äänismaa, Thomas Pfeifer, Stephane Delahaye, Ruben de Kanter, Tomohiko Ichikawa, Tetsuhiro Yamada, Alexander Treiber
The human pharmacokinetics of selexipag after oral dosing have been described in several studies (Baldoni et al., 2015; Bruderer et al., 2014; Hoch et al., 2015). Selexipag is rapidly absorbed and is hydrolysed to its active metabolite ACT-333679. Maximum observed plasma concentrations of selexipag and ACT-333679 are reached within 1–3 h and 3–4 h, respectively. A study after intravenous dosing of 200 µg selexipag was performed to determine its absolute bioavailability which was 49% (Kaufmann et al., 2017). In healthy subjects and in patients with PAH, plasma exposure to ACT-333679 at all doses and at steady-state is approximately 3-to 4-fold higher than to the parent compound. In the study after intravenous dosing of selexipag, the mean exposure ratio of ACT-333679 to selexipag was approximately 1.3. These data indicate a pre-systemic formation of ACT-333679, potentially by intestinal CES. Indeed, it is known that in man CES enzymes are expressed in the liver and in the gut and exist as different isoenzymes. CES1 is mostly expressed in the liver, while CES2 is present in the liver and the intestine (Yang et al., 2009). A pre-systemic contribution of CES2 to the formation of ACT-333679 is therefore likely.
How should a physician approach the pharmacological management of chronic thromboembolic pulmonary hypertension?
Published in Expert Opinion on Pharmacotherapy, 2021
Zhuang Tian, Xin Jiang, Zhi-Cheng Jing
Selexipag is a prostacyclin IP receptor agonist and approved in many countries for the treatment of PAH. SELECT study aims to assess the efficacy and safety of selexipag in subjects with inoperable or persistent/recurrent CTEPH with or without combinational therapy. The best therapeutic strategy for inoperable patients with CTEPH has not been established yet. RACE study and MR BPA [40] are currently ongoing trials, which compare the efficacy of riociguat with BPA for technically inoperable patients with CTEPH. The results may help us establish the optimal treatment option for the management of inoperable patients.