Abstract
-
▴ Iloprost is a stable prostacyclin analogue with a pharmacokinetic profile allowing nebulised administration in patients with primary pulmonary hypertension (PPH).
-
▴ Inhaled iloprost is a potent acute pulmonary vasodilator with a duration of action of about 60 minutes. It may exert additional long-term benefit through antiproliferative and antithrombotic effects.
-
▴ Inhaled iloprost 2.5 or 5μg six or nine times daily for 12 weeks (n = 101) significantly (p < 0.01) improved a combined clinical endpoint of a ≥10% increase in distance walked in 6 minutes and an improvement of ≥1 class in New York Heart Association functional class without clinical deterioration or death (16.8 versus 4.9% of placebo recipients, n = 102) in patients with severe PPH or selected forms of nonprimary pulmonary hypertension. Statistical analysis of the response for the PPH subgroup (20.8 versus 5.5% with placebo; n = 51 and 51) was not reported.
-
▴ Improvements from baseline in exercise capacity and haemodynamic/gas exchange variables have been reported in patients with PPH with continued use of inhaled iloprost. In addition, improvement in preinhalation vascular resistance occurred after 12 weeks of inhaled iloprost (p < 0.01 versus placebo) in a large randomised trial.
-
▴ Increased cough, headache, flushing and an influenza-like syndrome were the most common adverse events in the largest trial of patients receiving inhaled iloprost. Headache, flushing and jaw pain occurred significantly more frequently with inhaled iloprost than with placebo.
Similar content being viewed by others
Notes
The use of trade names is for product identification purposes only and does not imply endorsement.
References
Pass SE, Dusing ML. Current and emerging therapy for primary pulmonary hypertension. Ann Pharmacother 2002 Sep; 36(9): 1414–23
Gaine SP, Rubin LJ. Primary pulmonary hypertension [published erratum appears in Lancet 1999 Jan 2; 353: 74]. Lancet 1998 Aug 29; 352: 719–25
Runo JR, Loyd JE. Primary pulmonary hypertension. Lancet 2003 May 3; 361: 1533–44
De Backer TLM, Smedema J-P, Carlier SG. Current management of primary pulmonary hypertension. Biodrugs 2001; 15(12): 801–17
Klings ES, Farber HW. Current management of primary pulmonary hypertension. Drugs 2001; 61(13): 1945–56
Barst RJ, Rubin LJ, Long WA, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension: the Primary Pulmonary Hypertension Study Group. N Engl J Med 1996 Feb 1; 334(5): 296–301
Grant SM, Goa KL. Iloprost: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in peripheral vascular disease, myocardial ischaemia and extracorporeal circulation procedures. Drugs 1992 Jun; 43(6): 889–924
Olschewski H, Simonneau G, Galiè N, et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 2002 Aug 1; 347(5): 322–9
Clapp LH, Finney P, Turcato S, et al. Differential effects of stable prostacyclin analogs on smooth muscle proliferation and cyclic AMP generation in human pulmonary artery. Am J Respir Cell Mol Biol 2002 Feb; 26(2): 194–201
Wiedemann R, Ghofrani HA, Weissmann N, et al. Atrial natriuretic peptide in severe primary and nonprimary pulmonary hypertension: response to iloprost inhalation. J Am Coll Cardiol 2001 Oct; 38(4): 1130–6
Wilkens H, Bauer M, Forestier N, et al. Influence of inhaled iloprost on transpulmonary gradient of big endothelin in patients with pulmonary hypertension. Circulation 2003 Mar 25; 107(11): 1509–13
Olschewski H, Rohde B, Behr J, et al. Pharmacodynamics and pharmacokinetics of inhaled iloprost, aerolized by three different devices in severe pulmonary hypertension. Chest 2003 Oct; 124(4): 1294–304
Hoeper MM, Olschewski H, Ghofrani HA, et al. A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension: German PPH study group. J Am Coll Cardiol 2000 Jan; 35(1): 176–82
Galiè N, Manes A, Branzi A. The new clinical trials on pharmacological treatment in pulmonary arterial hypertension. Eur Respir J 2002 Oct; 20(4): 1037–49
Olschewski H, Ghofrani HA, Schmehl T, et al. Inhaled iloprost to treat severe pulmonary hypertension: an uncontrolled trial. German PPH Study Group. Ann Intern Med 2000 Mar 21; 132(6): 435–43
Hoeper MM, Schwarze M, Ehlerding S, et al. Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N Engl J Med 2000 Jun 22; 342(25): 1866–70
Ewert R, Wensel R, Opitz CF. Aerosolized iloprost for primary pulmonary hypertension [letter]. N Engl J Med 2000 Nov 9; 343(19): 1421–2
Opitz CF, Wensel R, Ewert R, et al. Preserved long-term efficacy of iloprost inhalation therapy over 2 years in patients with primary pulmonary hypertension [abstract no. 1113-52]. J Am Coll Cardiol 2000 Feb; 35 (2 Suppl. A): 286A
Behr J, Nikkho S, Borst M, et al. Long-term hemodynamic response in patients with pulmonary hypertension inhaling iloprost (AIR-2 study) [abstract no. 3535]. Eur Respir J 2003 Sep; 22 Suppl. 45: 562S
Wensel R, Opitz CF, Ewert R, et al. Effects of iloprost inhalation on exercise capacity and ventilatory efficiency in patients with primary pulmonary hypertension. Circulation 2000 May 23; 101(20): 2388–92
Blumberg FC, Riegger GA, Pfeifer M. Hemodynamic effects of aerosolized iloprost in pulmonary hypertension at rest and during exercise. Chest 2002 May; 121(5): 1566–71
Opitz CF, Wensel R, Bettmann M, et al. Assessment of the vasodilator response in primary pulmonary hypertension. Comparing prostacyclin and iloprost administered by either infusion or inhalation. Eur Heart J 2003 Feb; 24(4): 356–65
Olschewski H, Walmrath D, Schermuly R, et al. Aerosolized prostacyclin and iloprost in severe pulmonary hypertension. Ann Intern Med 1996 May 1; 124(9): 820–4
Pepke-Zaba J, Parameshwar J, Eiskjaer H, et al. A comparison of three month’s treatment with nebulised iloprost (Ilo) and continuous intravenous prostacyclin (PGI2) infusion for severe pulmonary hypertension (PH) [abstract no. P2836]. Eur Respir J 2000 Aug; 16 Suppl. 31: 395S
Petkov V, Ziesche R, Mosgoeller W, et al. Aerosolised iloprost improves pulmonary haemodynamics in patients with primary pulmonary hypertension receiving continuous epoprostenol treatment. Thorax 2001 Sep; 56(9): 734–6
Ghofrani HA, Rose F, Schermuly RT, et al. Amplification of the pulmonary vasodilatory response to inhaled iloprost by subthreshold phosphodiesterase types 3 and 4 inhibition in severe pulmonary hypertension. Crit Care Med 2002 Nov; 30(11): 2489–92
Ghofrani HA, Wiedemann R, Rose F, et al. Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension. Ann Intern Med 2002 Apr 2; 136(7): 515–22
Wilkens H, Guth A, König J, et al. Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Circulation 2001 Sep 11; 104(11): 1218–22
Gessler T, Schmehl T, Rose F, et al. Co-application of oxygen improves iloprost inhalation in pulmonary hypertension patients with long-term oxygen therapy [abstract no. 2163]. Eur Respir J Suppl 2001 Sep; 18 Suppl. 33: 324S
Beghetti M, Reber G, de MP, et al. Aerosolized iloprost induces a mild but sustained inhibition of platelet aggregation. Eur Respir J 2002 Mar; 19(3): 518–24
Schermuly RT, Schulz A, Ghofrani HA, et al. Pharmacokinetics and metabolism of infused versus inhaled iloprost in isolated rabbit lungs. J Pharmacol Exp Ther 2002 Nov; 303(2): 741–5
The European Agency for the Evaluation of Medicinal Products. Ventavis®: summary of product characteristics [online]. Available from URL: http://www.emea.eu.int [Accessed 2004 Jan 28]
Nicolini FA, Mehta JL, Nicholds WW, et al. Prostacyclin analogue iloprost decreases thrombolytic potential of tissue-type plasminogen activator in canine coronary thrombosis. Circulation 1990 Mar; 81(3): 1115–22
Kerins DM, Roy L, Kunitada S, et al. Pharmacokinetics of tissue-type plasminogen activator during acute myocardial infarction in men. Effect of a prostacyclin analogue [published erratum appears in Circulation 1992 Aug; 86(2): 698]. Circulation 1992; 85(2): 526–32
Penin E, Cheymol G, Bouslama K, et al. No pharmacokinetic interaction between iloprost and digoxin. Eur J Clin Pharmacol 1991; 41(5): 505–6
Nikkho S, Seeger W, Baumgartner R, et al. One-year observation of iloprost inhalation therapy in patients with pulmonary hypertension [abstractno. 2164]. Eur Respir J Suppl 2001 Sep; 18 Suppl. 33: 324S
Hoeper MM, Spiekerkoetter E, Westerkamp V, et al. Intravenous iloprost for treatment failure of aerosolised iloprost in pulmonary arterial hypertension. Eur Respir J 2002 Aug; 20(2): 339–43
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Goldsmith, D.R., Wagstaff, A.J. Inhaled Iloprost. Drugs 64, 763–773 (2004). https://doi.org/10.2165/00003495-200464070-00009
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-200464070-00009