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?
The cost of epoprostenol is approximately $100,000 per year but
may be higher depending upon patient dose. 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.
