Treatments for Pulmonary Hypertension
Issued by PHA’s Scientific Leadership Council
Last Updated June 2005
What is epoprostenol?
Epoprostenol is an intravenous medication used to treat pulmonary arterial hypertension (PAH). It is a synthetic (not obtained from other humans or animals) form of a substance made by the body called prostacyclin. It was approved by the FDA in 1996 for the treatment of pulmonary arterial hypertension in patients with New York Heart Association Class III or IV symptoms.
How does epoprostenol work?
Epoprostenol dilates blood vessels, prevents the smooth muscle cells in their walls from contracting, and reduces the stickiness of circulating platelets which might otherwise sludge up the vessel. It also helps the right side of the heart to better pump blood through the lungs. There is evidence that prostacyclin production is reduced in patients with pulmonary arterial hypertension (PAH). Improvement in exercise capacity and sense of well-being has been demonstrated in short-term studies of epoprostenol. Studies also showed improvement in survival in patients with idiopathic PAH. Several longer-term series have suggested significant survival benefit when compared to predicted survival or to historical untreated control patients.
How is epoprostenol given?
Epoprostenol is given by continuous intravenous infusion through a permanent catheter placed in one of the large veins going to the heart. It must be given this way because epoprostenol lasts for only a very short time (3-5 minutes) in the bloodstream. A pump (the CADD Legacy pump) is used to deliver the drug. The drug comes as a powder and must be dissolved in a special alkaline solution (diluent) which increases its stability in the bloodstream. The drug solution is then put in a cassette which attaches to the pump. If the solution is to be kept longer than 8 hours, it must also be kept cool, usually by means of freezer cold packs placed around the cassette.
Epoprostenol must be initiated in a setting with adequate personnel and equipment monitoring and emergency care. At most centers, patients are started on epoprostenol in the hospital. A dedicated nurse clinician is mandatory to help manage problems related to side effects of epoprostenol and to ensure appropriate dosing. In addition, the nurse clinician must teach patients how to mix epoprostenol, keep the central venous catheter clean, and manage the delivery pumps.
Dosing of epoprostenol:
Epoprostenol is dosed according to a patient's body weight, in kilograms (kg). The starting dose is generally 1-2 nanograms (ng) per kg per minute. The dose is increased according to the response and side effects of each patient. Usual long-term doses range from 20-40 ng per kg per minute.
What are the major problems with epoprostenol?
A major risk is interruption of the infusion, which in some patients can cause severe worsening of their PAH and even death, in just a few minutes. Therefore, patients should always have a prepared backup medication cassette and an infusion pump nearby. In an urgent situation, epoprostenol can be given through a peripheral vein.
A second major risk is that of infection related to the chronically indwelling intravenous catheter. The infections may involve the catheter site or the catheter itself, and this may lead to an infection in the blood stream. Any sign of infection warrants immediate medical attention. The infusion must be prepared daily, which can occupy up to an hour of time.
What are the frequent side effects of epoprostenol?
Epoprostenol infusion causes a variety of systemic side effects, partly related to its action as a vasodilator. These include headache, flushing, jaw pain, bone pain, diarrhea, palpitations, and rashes. The number and severity of side effects varies among patients.
How is epoprostenol supplied?
Epoprostenol is supplied as a powder in concentrations of 0.5 mg and 1.5 mg. The alkaline solution or diluent is provided in 50 ml vials. Epoprostenol is then dissolved in the diluent. Each container of dissolved epoprostenol can be used one time only. Once dissolved, the medication can be stored cold for up to 48 hours.
How do patients obtain epoprostenol?
Epoprostenol must be prescribed by a physician and insurance approval must be obtained prior to starting therapy. Once approved by insurance, epoprostenol is then sent directly to patients by either of the two specialty pharmacies: Accredo Health Inc. or Caremark.
Will insurance pay for epoprostenol?
Most insurance, as well as Medicaid and Medicare, will pay for epoprostenol.
Could a patient be allergic to epoprostenol?
There are no reports of this and it is unlikely that this would occur since prostacyclin is made by the body. Patients may, however, develop severe side effects (listed above). No medications are prohibited with the use of epoprostenol.
Use in children:
Epoprostenol has been used in children and appears to be safe. Clinical studies of epoprostenol did not include sufficient numbers of patients 16 years of age and under to determine whether they respond differently from older patients.
Pregnant and nursing women:
Epoprostenol has not been studied in pregnant women. It has not been shown to cause birth defects or other problems in animals. It is not known whether this drug is excreted in breast milk.