Epoprostenol (Veletri®, Caripul®): A Review of Its Use in Patients with Pulmonary Arterial Hypertension
Tóm tắt
A bioequivalent formulation of intravenous epoprostenol containing the excipients arginine and sucrose (epoprostenol AS) (Veletri®, Caripul®) is approved in the USA, UK, and other countries for the treatment of pulmonary arterial hypertension (PAH), and has improved thermal stability compared with epoprostenol containing glycine and mannitol (epoprostenol GM) (Flolan®). Epoprostenol, a synthetic prostacyclin, is a potent pulmonary vasodilator. Epoprostenol GM was originally approved for use as a long-term continuous infusion in patients with PAH nearly 20 years ago in the USA; however, this formulation has limited stability at room temperature, and requires the use of cooling or frequent medication changes during administration. The prolonged thermal stability of epoprostenol AS compared with epoprostenol GM allows for its extended administration at room temperature and/or refrigerated storage of prepared solutions. This article summarizes the pharmacology of epoprostenol AS and reviews its therapeutic use in adult patients with PAH. In clinical trials, epoprostenol AS provided sustained efficacy in terms of hemodynamic and symptomatic outcomes, and was generally well tolerated after transitioning from stable epoprostenol GM therapy and during an open-label extension study. Furthermore, there was a significant increase in the treatment convenience with epoprostenol AS compared with epoprostenol GM. Therefore, epoprostenol AS is a valuable therapeutic option that has the potential to overcome some of the limitations of long-term intravenous epoprostenol therapy in patients with PAH.
Tài liệu tham khảo
Waxman AB, Zamanian RT. Pulmonary arterial hypertension: new insights into the optimal role of current and emerging prostacyclin therapies. Am J Cardiol. 2013;111(5 Suppl):1A–16A.
Hoeper MM, Bogaard HJ, Condliffe R, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D42–50.
Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D34–41.
Jiang X, Jing ZC. Epidemiology of pulmonary arterial hypertension. Curr Hypertens Rep. 2013;15(6):638–49.
Galie N, Hoeper MM, Humbert M, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2009;34(6):1219–63.
Sitbon O, Simonneau G. Optimal management of severe pulmonary arterial hypertension. Eur Respir Rev. 2011;20(122):254–61.
Seferian A, Simonneau G. Therapies for pulmonary arterial hypertension: where are we today, where do we go tomorrow? Eur Respir Rev. 2013;22(129):217–26.
Actelion Pharmaceuticals UK Ltd. UK summary of product characteristics for Veletri, 0.5 mg, powder for solution for infusion. 2014. http://www.medicines.org.uk/emc/medicine/27736/SPC. Accessed 29 Sept 2014.
Actelion Pharmaceuticals US Inc. Veletri (epoprostenol) for injection: US prescribing information. 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022260s005lbl.pdf. Accessed 29 Sept 2014.
Actelion Pharmaceuticals Ltd. Actelion obtains marketing approval for Epoprostenol “ACT” in Japan [media release]. http://www.actelion.com/en/our-company/news-and-events/index.page?newsId=1678832. Accessed 18 Feb 2013.
Safdar Z. Treatment of pulmonary arterial hypertension: the role of prostacyclin and prostaglandin analogs. Respir Med. 2011;105(6):818–27.
Rubin LJ, Mendoza J, Hood M, et al. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Results of a randomized trial. Ann Intern Med. 1990;112(7):485–91.
Barst RJ, Rubin LJ, Long WA, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med. 1996;334(5):296–301.
Galie N, Corris PA, Frost A, et al. Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D60–72.
Barst RJ, Gibbs JS, Ghofrani HA, et al. Updated evidence-based treatment algorithm in pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54(1 Suppl):S78–84.
Farber HW, Miller DP, Meltzer LA, et al. Treatment of patients with pulmonary arterial hypertension at the time of death or deterioration to functional class IV: insights from the REVEAL registry. J Heart Lung Transplant. 2013;32(11):1114–22.
Badesch DB, Raskob GE, Elliott CG, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL registry. Chest. 2010;137(2):376–87.
Sitbon O, Delcroix M, Bergot E, et al. EPITOME-2: an open-label study assessing the transition to a new formulation of intravenous epoprostenol in patients with pulmonary arterial hypertension. Am Heart J. 2014;167(2):210–7.
Lambert O, Bandilla D, Iyer R, et al. Stability and microbiological properties of a new formulation of epoprostenol sodium when reconstituted and diluted. Drug Des Dev Ther. 2012;6:61–70.
Lambert O, Bandilla D. Stability and preservation of a new formulation of epoprostenol sodium for treatment of pulmonary arterial hypertension. Drug Des Dev Ther. 2012;6:235–44.
Chin KM, Badesch DB, Robbins IM, et al. Two formulations of epoprostenol sodium in the treatment of pulmonary arterial hypertension: EPITOME-1 (epoprostenol for injection in pulmonary arterial hypertension), a phase IV, open-label, randomized study. Am Heart J. 2014;167(2):218–25.e1.
Mubarak KK. A review of prostaglandin analogs in the management of patients with pulmonary arterial hypertension. Respir Med. 2010;104(1):9–21.
Szczeklik J, Szczeklik A, Nizankowski R. Haemodynamic changes induced by prostacyclin in man. Br Heart J. 1980;44(3):254–8.
Rubin LJ, Groves BM, Reeves JT, et al. Prostacyclin-induced acute pulmonary vasodilation in primary pulmonary hypertension. Circulation. 1982;66(2):334–8.
Nicolas LB, Krause A, Gutierrez MM, et al. Integrated pharmacokinetics and pharmacodynamics of epoprostenol in healthy subjects. Br J Clin Pharmacol. 2012;74(6):978–89.
Nicolas LB, Gutierrez MM, Dingemanse J. Comparative pharmacokinetic, pharmacodynamic, safety, and tolerability profiles of 3 different formulations of epoprostenol sodium for injection in healthy men. Clin Ther. 2013;35(4):440–9.
Chaumais MC, Jobard M, Huertas A, et al. Pharmacokinetic evaluation of continuous intravenous epoprostenol. Expert Opin Drug Metab Toxicol. 2010;6(12):1587–98.
Brash AR, Jackson EK, Saggese CA, et al. Metabolic disposition of prostacyclin in humans. J Pharmacol Exp Ther. 1983;226(1):78–87.
Carlton LD, Patterson JH, Mattson CN, et al. The effects of epoprostenol on drug disposition. I: a pilot study of the pharmacokinetics of digoxin with and without epoprostenol in patients with congestive heart failure. J Clin Pharmacol. 1996;36(3):247–56.
Carlton LD, Patterson JH, Mattson CN, et al. The effects of epoprostenol on drug disposition. II: a pilot study of the pharmacokinetics of furosemide with and without epoprostenol in patients with congestive heart failure. J Clin Pharmacol. 1996;36(3):257–64.
Tamura Y, Ono T, Fukuda K, et al. Evaluation of a new formulation of epoprostenol sodium in Japanese patients with pulmonary arterial hypertension (EPITOME4). Adv Ther. 2013;30(5):459–71.
Jensen KW, Kerr KM, Fedullo PF, et al. Pulmonary hypertensive medical therapy in chronic thromboembolic pulmonary hypertension before pulmonary thromboendarterectomy. Circulation. 2009;120(13):1248–54.
Delcroix M, Simonneau G, Bergot E, et al. Long-term safety of a new formulation of epoprostenol in pulmonary arterial hypertension [abstract no. P4080]. Eur Respir J. 2013;42(Suppl. 57):863s–4s.
GlaxoSmithKline. FLOLAN® (epoprostenol sodium) for injection: prescribing information. 2011. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020444s018lbl.pdf. Accessed 29 Sept 2014.
Farber HW, Frantz RP, Schilz R, et al. The PROSPECT registry: study design, patient characteristics, and treatment patterns [abstract no. A2499]. Am J Respir Crit Care Med. 2012;185.
Simonneau G, Rubin LJ, Galie N, et al. Long-term sildenafil added to intravenous epoprostenol in patients with pulmonary arterial hypertension. J Heart Lung Transplant. 2014;33(7):689–97.
Sitbon O, Jais X, Savale L, et al. Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study. Eur Respir J. 2014;43(6):1691–7.