Iloprost

Iloprost is a prescription drug used for the treatment of pulmonary arterial hypertension (PAH). PAH is a condition characterized by a sustained increase in the blood pressure in the arteries feeding the lungs. Iloprost belongs to a family of drugs known as prostacyclin analogs. Other members of this family include betaprost and treprostinil.

Other Names

• Ventavis

Uses

Iloprost is specifically indicated for the treatment of pulmonary arterial hypertension in patients with New York Heart Association (NYHA) Class III or IV symptoms. These symptoms are defined by:

• NYHA Class III patients have marked limitation of activity; they are comfortable only at rest.

• NYHA Class IV patients experience discomfort with any physical activity and symptoms occur even at rest.

How Iloprost is Taken

Iloprost is inhaled using an inhalation device called an I-neb AAD. AAD stands for Adaptive Aerosol Delivery.

The first recommended inhaled dose is 2.5 mcg. If this dose is well tolerated, dosing is increased to 5.0 mcg and maintained at that dose; otherwise the dose is maintained at 2.5 mcg.

Iloprost is taken 6-9 times per day (no more than once every 2 hours) during waking hours, according to need and patient tolerance. The maximum daily dose evaluated in clinical studies was 45 mcg (5.0 mcg 9 times per day).

How It Works

Iloprost is a synthetic analogue of prostacyclin PGI2. It dilates systemic and pulmonary arterial vascular beds.

This dilation of the pulmonary arterial beds reduces the increased pulmonary arterial pressure evident in PAH.

How the Body Affects Iloprost

Iloprost is metabolized principally into tetranor-iloprost, an inactive metabolite. The liver cytochrome P-450 system is not significantly involved in this metabolism.

68% and 12% of the original dose is excreted in the urine and feces, respectively.

Side Effects

The most commonly observed side effects in adults (occurring in ≥ 3% of treated patients) are:

• Vasodilation (flushing)
• Cough
• Headache
• Trismus (lockjaw)
• Insomnia
• Nausea
• Hypotension (low blood pressure)
• Vomiting
• Abnormal lab tests
• Flusyndrome
• Back pain
• Tongue pain
• Heart palpitations
• Dizziness and fainting
• Muscle cramps
• Hemoptysis (blood in cough sputum)
• Pneumonia

Side Effects

Iloprost has blood pressure lowering effects. These effects may cause dizziness, lightheadedness, and fainting.

Risks

Interactions

Due to its blood pressure-lowering effects, iloprost is to be used cautiously with vasodilators and antihypertensive medications.

Effectiveness

One study published in the New England Journal of Medicine demonstrated that inhaled iloprost is an effective therapy for patients with severe pulmonary hypertension.^[1]

History

Iloprost is manufactured in the U.S. by Actelion Pharmaceuticals under the brand name Ventavis. FDA approval was granted in 2004.

In August, 2009 the US Food and Drug Administration (FDA) approved a new 20 microgram per milliliter (mcg/ml) formulation of Ventavis® as a therapy for New York Heart Association Class III and IV pulmonary arterial hypertension (PAH). This new increased 20 mcg/ml strength formulation will deliver the same dose in half the volume which is expected to reduce inhalation time and further support patient compliance.†

Research

Recent discoveries

• A recent study showed that iloprost works on the E4 receptor when the IP receptor is impaired due to pulmonary hypertension. The E4 receptor is a previously unknown site of action. ^[2]
• Iloprost may also have a role in controlling pulmonary hypertension after cardiac surgery. ^{[3] [4]}

Future research

• The "VISION" Trial: Ventavis Inhalation With Sildenafil to Improve and Optimize Pulmonary Arterial Hypertension is ongoing but no longer recruiting participants. ^[5]
• To test whether the addition of inhaled iloprost is safe and effective in patients with idiopathic pulmonary arterial hypertension who are already being treated with the endothelin receptor antagonist bosentan. ^[6]

Clinical Trials

A list of ongoing trials is available at ClinicalTrials.gov: iloprost trials.

References

†Data based on an in vitro study with a manually generated 28.3-L/min, 15-sec inhalation cycle breathing pattern.

1. ↑ Olschewski H, Simonneau G, Galiè N. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med. 2002 Aug 1;347(5):322-9. Abstract | Full Text
2. ↑ Lai YJ, Pullamsetti SS, Dony E, et al. Role of the prostanoid EP4 receptor in iloprost-mediated vasodilatation in pulmonary hypertension. Am J Repir Crit Care Med. 2008 Jul 15;178(2):188-96. Epub 2008 May 8. Abstract
3. ↑ Winterhalter M, Simon A, Fischer S. Comparison of inhaled iloprost and nitric oxide in patients with pulmonary hypertension during weaning from cardiopulmonary bypass in cardiac surgery: a prospective randomized trial. J Cardiothorac Vasc Anesth. 2008 Jun;22(3):406-13. Epub 2008 Jan 22. Abstract
4. ↑ Rex S, Schaelte G, Metzelder S, et al. Inhaled iloprost to control pulmonary artery hypertension in patients undergoing mitral valve surgery: a prospective, randomized-controlled trial. Acta Anaesthesiol Scand. 2008 Jan;52(1):65-72. Epub 2007 Nov 1. Abstract
5. ↑ ClinicalTrials.gov. The "VISION" Trial: Ventavis Inhalation With Sildenafil to Improve and Optimize Pulmonary Arterial Hypertension
6. ↑ ClinicalTrials.gov. Combination Therapy of Bosentan and Aerosolized Iloprost in Idiopathic Pulmonary Arterial Hypertension (IPAH)

External Links

FDA: Patient Information Sheet