References

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VENTAVIS® (iloprost) full Prescribing Information. Actelion Pharmaceuticals US, Inc., November 2013.


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Denyer J, Nikander K, Smith NJ. Adaptive Aerosol Delivery (AAD) technology. Expert Opin Drug Deliv. 2004;1:165-176.


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Hardaker LE, Hatley RH. In vitro characterization of the I-neb Adaptive Aerosol Delivery (AAD) System. J Aerosol Med Pulm Drug Deliv. 2010;23(Suppl 1):S11-S20.


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Olschewski H, Simonneau G, Galie N, et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med. 2002;347:322-329.


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Lai YC, Potoka KC, Champion HC, Mora AL, Gladwin MT. Pulmonary arterial hypertension. The clinical syndrome. Circ Res. 2014;115:115-130.


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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.


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Badesch DB, McLaughlin W, Delcroix M, et al. Prostanoid therapy for pulmonary arterial hypertension. J Am Coll Cardiol. 2004;43:56-61.


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Giald A, Yanagisawa M, Langleben D, et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med. 1993;328:1732-1739.


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Vane JR, Bottlin RM. Pharmacodynamic profile of prostacyclin. Am J Cardiol. 1995;75:3A-10A.


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McLaughlin VV, Shah SJ, Souza R, et al. Management of pulmonary arterial hypertension. J Am Coll Cardiol. 2015;65:1977-1997.


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Clapp LH, Finney P, Turcato S, Tran S, Rubin LJ, Tinker A. 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;26:194-201.


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Data on file, Actelion Pharmaceuticals.


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McLaughlin VV, Oudiz RJ, Frost A, et al. Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2006;174:1257-1263.


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Nikander K, Denyer J. Adaptive Aerosol Delivery (AAD) technology. In: Rathbone MJ, Hadgraft J, Roberts MS, eds. Modified-Release Drug Delivery Technology. New York, NY: Marcel Dekker, Inc. February 2011.


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Olschewski H, Rohde B, Berhr J, et al. Pharmacodynamics and pharmacokinetics of inhaled iloprost, aerosolized by three different devices, in severe pulmonary hypertension. Chest. 2003;124;1294-1304.


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Simonneau G, Gatzoulis MA, Adatia A, et al. Updated Clinical Classification of Pulmonary Hypertension. J Am Coll Cardiol. 2013; 62(25 suppl D): D34-D41.


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INDICATION

VENTAVIS® (iloprost) Inhalation Solution is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve a composite endpoint consisting of exercise tolerance, symptoms (NYHA Class), and lack of deterioration. Studies establishing effectiveness included predominantly patients with NYHA Functional Class III-IV symptoms and etiologies of idiopathic or heritable PAH (65%) or PAH associated with connective tissue disease (23%).

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Risk of Syncope

  • Vital signs should be monitored while initiating VENTAVIS. Hypotension leading to syncope has been observed; VENTAVIS should therefore not be initiated in patients with systolic blood pressure less than 85 mmHg.

Pulmonary Venous Hypertension

  • Stop VENTAVIS immediately if signs of pulmonary edema occur; this may be a sign of pulmonary venous hypertension.

Bronchospasm

  • VENTAVIS inhalation may cause bronchospasm and patients with a history of hyperreactive airway disease may be more sensitive.

ADVERSE REACTIONS

Serious Adverse Events

  • Serious adverse events reported include congestive heart failure, chest pain, supraventricular tachycardia, dyspnea, peripheral edema, and kidney failure.

Adverse Events

  • Adverse events reported in a Phase 3 clinical trial occurring with a ≥3% difference between VENTAVIS patients and placebo patients were vasodilation (flushing) (27% vs 9%), increased cough (39% vs 26%), headache (30% vs 20%), trismus (12% vs 3%), insomnia (8% vs 2%), nausea (13% vs 8%), hypotension (11% vs 6%), vomiting (7% vs 2%), alkaline phosphatase increased (6% vs 1%), flu syndrome (14% vs 10%), back pain (7% vs 3%), tongue pain (4% vs 0%), palpitations (7% vs 4%), syncope (8% vs 5%), GGT increased (6% vs 3%), muscle cramps (6% vs 3%), hemoptysis (5% vs 2%), and pneumonia (4% vs 1%).

DRUG INTERACTIONS

Antihypertensives and Vasodilators

  • VENTAVIS has the potential to increase the hypotensive effect of vasodilators and antihypertensive agents.

Anticoagulants and Platelet Inhibitors

  • VENTAVIS also has the potential to increase risk of bleeding, particularly in patients maintained on anticoagulants or platelet inhibitors.

Please see full Prescribing Information.

INDICATION

VENTAVIS® (iloprost) Inhalation Solution is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve a composite endpoint consisting of exercise tolerance, symptoms (NYHA Class), and lack of deterioration. Studies establishing effectiveness included predominantly patients with NYHA Functional Class III-IV symptoms and etiologies of idiopathic or heritable PAH (65%) or PAH associated with connective tissue disease (23%).

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Risk of Syncope

  • Vital signs should be monitored while initiating VENTAVIS. Hypotension leading to syncope has been observed; VENTAVIS should therefore not be initiated in patients with systolic blood pressure less than 85 mmHg.

Pulmonary Venous Hypertension

  • Stop VENTAVIS immediately if signs of pulmonary edema occur; this may be a sign of pulmonary venous hypertension.

Bronchospasm

  • VENTAVIS inhalation may cause bronchospasm and patients with a history of hyperreactive airway disease may be more sensitive.

ADVERSE REACTIONS

Serious Adverse Events

  • Serious adverse events reported include congestive heart failure, chest pain, supraventricular tachycardia, dyspnea, peripheral edema, and kidney failure.

Adverse Events

  • Adverse events reported in a Phase 3 clinical trial occurring with a ≥3% difference between VENTAVIS patients and placebo patients were vasodilation (flushing) (27% vs 9%), increased cough (39% vs 26%), headache (30% vs 20%), trismus (12% vs 3%), insomnia (8% vs 2%), nausea (13% vs 8%), hypotension (11% vs 6%), vomiting (7% vs 2%), alkaline phosphatase increased (6% vs 1%), flu syndrome (14% vs 10%), back pain (7% vs 3%), tongue pain (4% vs 0%), palpitations (7% vs 4%), syncope (8% vs 5%), GGT increased (6% vs 3%), muscle cramps (6% vs 3%), hemoptysis (5% vs 2%), and pneumonia (4% vs 1%).

DRUG INTERACTIONS

Antihypertensives and Vasodilators

  • VENTAVIS has the potential to increase the hypotensive effect of vasodilators and antihypertensive agents.

Anticoagulants and Platelet Inhibitors

  • VENTAVIS also has the potential to increase risk of bleeding, particularly in patients maintained on anticoagulants or platelet inhibitors.

Please see full Prescribing Information.