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Published in: American Journal of Cardiovascular Drugs 6/2014

01-12-2014 | Adis Drug Evaluation

Epoprostenol (Veletri®, Caripul®): A Review of Its Use in Patients with Pulmonary Arterial Hypertension

Authors: Sarah L. Greig, Lesley J. Scott, Greg L. Plosker

Published in: American Journal of Cardiovascular Drugs | Issue 6/2014

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Abstract

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.
Literature
1.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
2.
go back to reference Hoeper MM, Bogaard HJ, Condliffe R, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D42–50.PubMedCrossRef Hoeper MM, Bogaard HJ, Condliffe R, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D42–50.PubMedCrossRef
3.
go back to reference Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D34–41.PubMedCrossRef Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D34–41.PubMedCrossRef
4.
go back to reference Jiang X, Jing ZC. Epidemiology of pulmonary arterial hypertension. Curr Hypertens Rep. 2013;15(6):638–49.PubMedCrossRef Jiang X, Jing ZC. Epidemiology of pulmonary arterial hypertension. Curr Hypertens Rep. 2013;15(6):638–49.PubMedCrossRef
5.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
6.
go back to reference Sitbon O, Simonneau G. Optimal management of severe pulmonary arterial hypertension. Eur Respir Rev. 2011;20(122):254–61.PubMedCrossRef Sitbon O, Simonneau G. Optimal management of severe pulmonary arterial hypertension. Eur Respir Rev. 2011;20(122):254–61.PubMedCrossRef
7.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
11.
go back to reference Safdar Z. Treatment of pulmonary arterial hypertension: the role of prostacyclin and prostaglandin analogs. Respir Med. 2011;105(6):818–27.PubMedCrossRef Safdar Z. Treatment of pulmonary arterial hypertension: the role of prostacyclin and prostaglandin analogs. Respir Med. 2011;105(6):818–27.PubMedCrossRef
12.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
13.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
14.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
15.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
16.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
17.
go back to reference Badesch DB, Raskob GE, Elliott CG, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL registry. Chest. 2010;137(2):376–87.PubMedCrossRef Badesch DB, Raskob GE, Elliott CG, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL registry. Chest. 2010;137(2):376–87.PubMedCrossRef
18.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
19.
go back to reference 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.CrossRef 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.CrossRef
20.
go back to reference 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.CrossRef 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.CrossRef
21.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
22.
go back to reference Mubarak KK. A review of prostaglandin analogs in the management of patients with pulmonary arterial hypertension. Respir Med. 2010;104(1):9–21.PubMedCrossRef Mubarak KK. A review of prostaglandin analogs in the management of patients with pulmonary arterial hypertension. Respir Med. 2010;104(1):9–21.PubMedCrossRef
24.
go back to reference Rubin LJ, Groves BM, Reeves JT, et al. Prostacyclin-induced acute pulmonary vasodilation in primary pulmonary hypertension. Circulation. 1982;66(2):334–8.PubMedCrossRef Rubin LJ, Groves BM, Reeves JT, et al. Prostacyclin-induced acute pulmonary vasodilation in primary pulmonary hypertension. Circulation. 1982;66(2):334–8.PubMedCrossRef
25.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
26.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
27.
go back to reference Chaumais MC, Jobard M, Huertas A, et al. Pharmacokinetic evaluation of continuous intravenous epoprostenol. Expert Opin Drug Metab Toxicol. 2010;6(12):1587–98.PubMedCrossRef Chaumais MC, Jobard M, Huertas A, et al. Pharmacokinetic evaluation of continuous intravenous epoprostenol. Expert Opin Drug Metab Toxicol. 2010;6(12):1587–98.PubMedCrossRef
28.
go back to reference Brash AR, Jackson EK, Saggese CA, et al. Metabolic disposition of prostacyclin in humans. J Pharmacol Exp Ther. 1983;226(1):78–87.PubMed Brash AR, Jackson EK, Saggese CA, et al. Metabolic disposition of prostacyclin in humans. J Pharmacol Exp Ther. 1983;226(1):78–87.PubMed
29.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
30.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
31.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
32.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
33.
go back to reference 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. 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.
35.
go back to reference 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. 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.
36.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
37.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
Metadata
Title
Epoprostenol (Veletri®, Caripul®): A Review of Its Use in Patients with Pulmonary Arterial Hypertension
Authors
Sarah L. Greig
Lesley J. Scott
Greg L. Plosker
Publication date
01-12-2014
Publisher
Springer International Publishing
Published in
American Journal of Cardiovascular Drugs / Issue 6/2014
Print ISSN: 1175-3277
Electronic ISSN: 1179-187X
DOI
https://doi.org/10.1007/s40256-014-0093-0

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Acknowledgement to Referees

Acknowledgement to Referees