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•      Prostacyclin in PAH

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Prostacyclin Therapy

Prostacyclin is a member of the family of lipid molecules known as eicosanoids. It is produced in endothelial cells from prostaglandin H₂ (PGH₂) by the action of the enzyme prostacyclin synthase.

PAH involves an imbalance in nitric oxide, endothelin, and prostacyclin. These three pathways interact with each other, modulating the effect of any single pathway.¹ Decreased levels of prostacyclin are a key pathological feature of PAH.² The addition of prostacyclin has been shown to play a critical role in the management of PAH, offering important clinical benefits.^3,4

Prostacyclin may play a role in3-12:

Action Potential benefit

Vasodilation Improved hemodynamics

Platelet aggregation inhibition Anticoagulation, inhibition of in situ thrombosis

Antiproliferation Improved pulmonary blood flow

Cardiac contractility Improved heart function

Anti-inflammatory Improved endothelial function

There are three medications in the prostacyclin group FDA approved for the treatment of pulmonary arterial hypertension (PAH):

1. Ventavis (iloprost) is a synthetic analogue of prostacyclin. The first inhaled dose should be 2.5 mcg (as delivered at the mouthpiece). If this dose is well tolerated, dosing should be increased to 5.0 mcg and maintained at that dose; otherwise maintain the dose at 2.5 mcg. Ventavis should be taken 6 to 9 times per day (no more than once every 2 hours) during waking hours, according to individual need and tolerability. The maximum daily dose evaluated in clinical studies was 45 mcg (5 mcg 9 times per day).¹³
2. Epoprostenol sodium is a synthetic prostacyclin. Continuous chronic infusion of FLOLAN^® should be administered through a central venous catheter. Temporary peripheral intravenous infusion may be used until central access is established. Chronic infusion of FLOLAN should be initiated at 2 ng/kg/min and increased in increments of 2 ng/kg/min every 15 minutes or longer until dose-limiting pharmacologic effects are elicited or until a tolerance limit to the drug is established and further increases in the infusion rate are not clinically warranted.¹⁴
3. PI (Dosage): Continuous chronic infusion of FLOLAN should be administered through a central venous catheter. Temporary peripheral intravenous infusion may be used until central access is established. Chronic infusion of FLOLAN should be initiated at 2 ng/kg/min and increased in increments of 2 ng/kg/min every 15 minutes or longer until dose-limiting pharmacologic effects are elicited or until a tolerance limit to the drug is established and further increases in the infusion rate are not clinically warranted.
4. Treprostinil sodium is supplied in 20 mL vials in concentrations of 1 mg/mL, 2.5 mg/mL, 5 mg/mL and 10 mg/mL. Remodulin^® can be administered as supplied or diluted for intravenous infusion with Sterile Water for Injection or 0.9% Sodium Chloride Injection prior to administration.¹⁵
5. PI (Dosage): Remodulin is supplied in 20 mL vials in concentrations of 1 mg/mL, 2.5 mg/mL, 5 mg/mL and 10 mg/mL. Remodulin can be administered as supplied or diluted for intravenous infusion with Sterile Water for Injection or 0.9% Sodium Chloride Injection prior to administration.

I-neb AAD System User Guide
The I-neb AAD System is a registered trademark of Philips Respironics.

For more information about the I-neb AAD System please see About the I-neb AAD System

1. McLaughlin VV, McGoon MD. Pulmonary arterial hypertension. Circulation. 2006:114:1417-1431.
2. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004;351:1425-1436.
3. Vane JR, Bottlin RM. Pharmacodynamic profile of prostacycline. Am J Cardiol. 1995;75:3A-10A.
4. Badesch DB, McLaughlin W, Delcroix M, et al. Prostanoid therapy for pulmonary arterial hypertension. J Am Coll Cardiol. 2004;43:56-61.
5. Tuder RM, Cool CD, Geraci MW, et al. Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med. 1999;159:1925-1932.
6. Montalescot G, Drobinski G, Meurin P, et al. Effects of prostacyclin on the pulmonary vascular tone and cardiac contractility of patients with pulmonary hypertension secondary to end-stage heart failure. Am J Cardiol. 1998;82:749-755.
7. Kerbaul F, Brimioulle S, Rondelet B, Dewachter C, Hubloue I, Naeije R. How prostacyclin improves cardiac output in right heart failure in conjunction with pulmonary hypertension. Am J Respir Crit Care Med. 2007;175:846-850.
8. Kemming G, Kisch-Wedel H, Flondor M, et al. Improved ventricular function during inhalation of PGI(2) aerosol partly relies on enhanced myocardial contractility. Eur Surg Res. 2005;37:9-17.
9. van Albada ME, Berger RM, Niggebrugge M, van Veghel R, Cromme-Dijkhuis AH, Schoemaker RG. Prostacyclin therapy increases right ventricular capillarisation in a model for flow-associated pulmonary hypertension. Eur J Pharmacol. 2006;549:107-116.
10. Pavlovic ´M, Petkovic´ D, Cvetkovic´ M, et al. The influence of prostacyclin (PGI2) on contractile properties of isolated right ventricle of rat heart. Experientia. 1995;51:941-944.
11. Pavlovic´M, Petkovic´ D, Cvetkovic´ M, Zdjelar K, Starcevic´ V, Bosnic´O. Study of the mechanism of prostacyclin (PGI2) action on myocardial contractility. Agents Actions Suppl. 1992;37:171-175.
12. Rose F, Hattar K, Gakisch S, et al. Increased neutrophil mediator release in patients with pulmonary hypertension-suppression by inhaled iloprost. Thromb Haemost. 2003;90:1141-1149.
13. Ventavis (iloprost) Full Prescribing Information. Actelion Pharmaceuticals US, Inc. 2009.
14. Flolan Information Center. Available at http://www.flolan-center.com/pages/Flolan_effective.html. Accessed October 04, 2007.
15. Remodulin Package Insert. February 2008.

For more information about
Ventavis, please call
1-866-ACTELION (1-866-228-3546).