Treatments for Pulmonary Hypertension
Issued by PHA’s Scientific Leadership Council. Information is based on the United States Food and Drug Administration drug labeling.
Last Updated February 2012
What is iloprost?
Iloprost is an inhaled medication indicated for the treatment of pulmonary arterial hypertension (PAH) in World Health Organization (WHO) Group 1 patients to improve a composite endpoint consisting of exercise tolerance, symptoms (NYHA Class), and lack of deterioration. Studies establishing effectiveness included predominately patients with NYHA Functional Class III-IV symptoms and etiologies of idiopathic or heritable PAH (65%) or PAH associated with connective tissue disease (23%).
Iloprost is marketed as Ventavis® for PAH and was approved by the Food and Drug Administration (FDA) in 2004.
Iloprost has also been given intravenously but is not FDA approved for use by this route.
It is a synthetic (not obtained from other humans or animals) analog of prostacyclin.
How does iloprost work?
The major action of iloprost is direct vasodilatation of the pulmonary vascular bed or relaxation and opening of narrowed blood vessels (arteries) in the lungs. It may also inhibit platelets from clumping together (aggregating). Relaxing and widening of the blood vessels in the lungs makes it easier for the heart to pump blood through the lungs. This reduces blood pressure in the lungs that should lead to improvement in physical activity level and well-being.
Iloprost showed clinical improvement as defined by 3 specific measurements: ability to exercise as measured by the 6-minute walk test, symptoms (NYHA Functional Class), and decrease in the worsening of PAH symptoms in a multi-center, short-term (12 week) randomized study conducted in 203 patients.
In a smaller safety study, 34 patients treated with both bosentan and iloprost for at least 16 weeks had improved symptoms (NYHA Functional Class) and decrease in the worsening of PAH symptoms.
How is iloprost given? (Please see package insert for full details)
The half-life of iloprost is 20 to 30 minutes and its effects generally last for about 1.5 hours. The medication is inhaled through the mouth a special device that delivers medication to your lungs: the I-neb® AAD® System.
The I-neb® AAD® system is a handheld, battery-powered drug delivery system. I-neb produces aerosol in a different way than conventional nebulizers; it does not require a supply of compressed air to drive the system. Aerosol is produced by vibrating mesh technology (VMT) within the medication chamber; when coupled with Adaptive Aerosol Delivery (AAD®) technology, results in a smaller, lighter, almost silent device that can nebulize faster than conventional nebulizers. The I-neb® AAD® system is operated by a disc that activates the system with information to tell the I-neb how to deliver the medication. The I-neb® AAD® System turns Ventavis® into an aerosol (mist) that you inhale into your lungs.
Iloprost is initiated at a dose of 2.5 micrograms (mcg) and increased to 5 mcg (the usual dose) if the patient tolerates the lower dose. Iloprost is given 6 to 9 times per day depending upon the response and activity level of each patient. Each inhalation takes approximately 6-10 minutes depending on the breathing pattern of each patient.
Your doctor may prescribe Ventavis® 20 mcg/mL if you have long treatment times and are maintained at the 5 mcg dose. The higher concentration of medicine lowers the amount of solution you need to take by 50%, which gives you shorter treatment time.
Because iloprost is an inhaled medication, patients should be careful not to expose others while taking a treatment. Patients should follow the manufacturer’s instructions for cleaning the I-neb® AAD® nebulizer system after each dose administration.
How is iloprost supplied? (Please see package insert for full details)
Iloprost comes in 1 mL glass vials (ampules) that can be stored at room temperature. There are 2 concentrations: 10 mcg/mL and 20 mcg/mL.
Based on the concentration, the delivered dose varies as in the table below.
2.5 mcg or 5.0 mcg from 1 ampule
5.0 mcg from 1 ampule
For each inhalation session, the entire contents of each opened ampule should be transferred into the I-neb® AAD® System medication chamber immediately before use.
For the 10 mcg/mL solution, one mL of the solution contains 0.01 mg iloprost, 0.81 mg ethanol, 0.121 mg tromethamine, 9.0 mg sodium chloride, and approximately 0.51 mg hydrochloric acid (for pH adjustment to 8.1) in water.
For the 20 mcg/mL solution, one mL of the solution contains 0.02 mg iloprost, 1.62 mg ethanol, 0.242 mg tromethamine, 9.0 mg sodium chloride, and approximately 0.76 mg hydrochloric acid (for pH adjustment to 8.4) in water.
How can a patient obtain iloprost?
Iloprost must be prescribed by a physician and insurance approval must be obtained prior to starting therapy. Once approved by insurance, iloprost is then sent directly to patients by either of two specialty pharmacies: Accredo Health Group, Inc. and CVS Caremark.
Will insurance pay for iloprost?
It is expected that most insurance plans will pay for iloprost prescriptions; however, plans with a set co-payment may result in additional cost to the patient.
Medicaid and most state-run insurance plans will pay for iloprost. Medicare will also cover iloprost in most cases under the part D component of that program.
Actelion PAH Pathways® (866-288-3546) offers a variety of options to cover either partial or full drug costs for any patient with qualifying financial circumstances. Caring Voice Coalition (888-267-1440), an organization that provides grants to assist with drug cost for patients with chronic illnesses, may also provide coverage if the patient qualifies for such assistance.
What are the frequent side effects of iloprost?
The most common side effects include flushing (vasodilation), increased cough, headache, spasm of jaw muscles that makes it difficult to open your mouth and may cause jaw discomfort (trismus), insomnia, nausea, low blood pressure, vomiting, increased alkaline phosphatase or GGT (liver enzymes measured in the blood), flu syndrome –like symptoms, back pain, tongue pain, fast or irregular heart rate or rhythm (palpitations), passing out (syncope), muscle cramps, coughing up blood (hemoptysis), and pneumonia.
Hypotension leading to syncope has been observed; iloprost should therefore not be initiated in patients with systolic blood pressure less than 85 mmHg.
Pulmonary venous hypertension and pulmonary edema can occur in which case iloprost should be promptly discontinued.
Iloprost inhalation can induce narrowed breathing tubes (airways), called bronchospasm, manifest as cough, wheezing or shortness of breath.
Iloprost solution can also irritate the eyes and skin. If iloprost comes in contact with the skin or eyes, rinse immediately with water.
How are side effects of iloprost monitored?
Vital signs should be monitored while initiating iloprost. Iloprost should generally be avoided if the systemic systolic blood pressure is below 85 mmHg.
If you experience any of the symptoms mentioned in the previous section, you should promptly notify your physician.
What are considerations for use of iloprost in special populations?
Iloprost has been shown to cause damage to the fetus (i.e. teratogenic) in rats. Iloprost has not been evaluated in pregnant women or women who are breastfeeding. Iloprost should be used in pregnant or nursing mothers only if the potential benefit justifies the risk to the fetus or infant.
Safety and efficacy in pediatric patients has not been established.
Clinical studies did not include a sufficient number of patients over age 65 to determine either safety or efficacy.
Iloprost has not been evaluated in patients with impaired liver (hepatic) function; however, consideration should be given to increasing the dosing interval (e.g. 3 to 4 hours between doses) in patients with moderate to severe hepatic impairment.
Iloprost has not been evaluated in patients with impaired kidney (renal) function. Likewise, the effect of dialysis in unknown.
Could a patient be allergic to iloprost?
This is unlikely. An ampule of iloprost does not contain preservatives or sulfites. However, any medication can cause side effects or sensitivities and patients should check with their doctor if they experience a problem.
What are important drug interactions with iloprost? (Please see package insert for full details)
Iloprost and other medicines may potentially affect each other, causing side effects.
There is potential risk when iloprost is used with medicines used to treat systemic high blood pressure or heart problems of low systemic blood pressure and passing out (syncope).
Iloprost has the potential to increase risk of bleeding, particularly in patients maintained on anticoagulants or platelet inhibitors (e.g. heparin, warfarin, clopidogrel, dabigatran).
Can iloprost be taken with other medications?
Iloprost is safe to take with most medications but can cause side effects that interfere with or require changes in other medications. Check all medications with your doctor.
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