Iloprost, a synthetic analogue of prostacyclin PGI2, and chemically known as 5-{(E)-(1S,5S,6R,7R)-7-hydroxy-6[(E)-(3S,4RS)-3-hydroxy-4-methyl-1-octen-6-inyl]-bicyclo[3.3.0]octan-3-ylidene}pentanoic acid, is a potent vasodilator aimed at treating patients with Pulmonary Arterial Hypertension (PAH) in order to improve their exercise ability and reduce or delay clinical worsening. It is also used in patients with scleroderma and Raynaud’s Phenomenon. It was originally developed by Schering AG, a German pharmaceutical company, who later merged with Bayer to form Bayer Healthcare Pharmaceuticals, who are now responsible for marketing the drug in the European Union, whereas Actelion Pharmaceuticals is responsible for marketing the drug in the United States. It is available both as inhalable (Ventavis) and intravenous (Ilomedine) formulations.

How Iloprost Works

Prostacyclin, also known as prostaglandin, is biosynthesized in the human vascular tissues easily, and has a paracrine mode of signalling on localised G protein-coupled receptors on endothelial cells and platelets. Those on the platelets become activated when binding to PGI2, which in turn activates adenylyl cyclase to produce cAMP which then prevents any undue platelet activation and counteracts production of excess calcium. Meanwhile, binding of PGI2 to G protein-coupled receptors on endothelial cells also increases cAMP levels in the cytosol, the latter activating protein kinase A (PKA). PKA is then involved in a series of dephosphorylation reactions which eventually causes the smooth muscles to relax and paves way for vasodilation. Iloprost, being a synthetic analogue of PGI2 works in a similar way when administered externally, and dilates the systemic and pulmonary vascular beds. This eases the growing blood pressure and reduces clinical progression.

Iloprost Clinical Trials and Approval

Ventavis was approved by the US FDA for treatment if PAH patients with functional class III and IV symptoms, as classified by the New York Heart Association (NYHA) on December 29th 2004. This came after a successful round of clinical trials, where a total of 203 patients with selected forms of severe PAH and chronic thromboembolic pulmonary hypertension, NYHA functional class III or IV, who were given doses of varying strengths, ranging from 2.5- or 5.0-micrograms 6 to 9 times daily, (the maximum tolerated dose being 30 micrograms a day), showed significant forms of improvement both in terms of exercising capability and reduction of clinical worsening at the end of 12 weeks.

Dosage for the inhaled formulation starts with 2.5 micrograms, inhaled 6 to 9 times daily (no more than every 2 hours), and if well tolerated, the dose might be increased to 5 micrograms at a time, 6 times daily. This should be done using either of the two compressed air nebulizers with AAD delivery systems (Halolite and Prodose) as well as with two ultrasonic nebulizers Ventaneb and I-Neb.

Iloprost Dosing and Indications

The intravenous form is usually administered diluted via a peripheral vein or central venous catheter for 3 days. This is typically repeated every 8 to 12 weeks, with the dosage varying according to the tolerance of the patients.

Common side-effects include back pain, dizziness, flushing, headache, increased cough, jaw tightness, light-headedness, muscle cramps, nausea, tongue pain, trouble while sleeping, vomiting and weakness. Children and the elderly should be under supervision while prescribing these drugs. Pregnant women or those planning to conceive are advised to avoid the use of such classes of drugs, unless prescribed otherwise. In case of severe adverse effects like severe allergic reactions, chest pain and coughing up blood, decreased urination, fainting, fast or irregular heartbeats, flu-like symptoms, jaw spasms or shortness of breath, sudden, unexplained weight gain, edema, trouble opening mouth, unusual bruising or bleeding or wheezing, a doctor is to be consulted immediately.

Note: Pulmonary Hypertension News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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