Last Updated June 2005
What is treprostinil?
Treprostinil is a subcutaneous (under the skin) or intravenous
(in the veins) medication used for the treatment of pulmonary
arterial hypertension (PAH). It is a synthetic (not obtained from
other humans or animals) analogue of prostacyclin (see epoprostenol
fact sheet for more information about prostacyclin). Treprostinil
was approved by the FDA in 2002 for subcutaneous use, and subsequently
in 2004 for intravenous use for the treatment of PAH in patients
with New York Heart Association Class II, III, or IV symptoms.
How does treprostinil work?
The major actions of treprostinil are vasodilatation of the pulmonary
and systemic vascular beds (widening of narrowed blood vessels
in the lung and other parts of the body), and inhibition of platelet
clumping (aggregation). These effects appear to be similar to
the effects of epoprostenol (Flolan). Improved exercise capacity
has been demonstrated in a short-term (3 month) study of subcutaneous
treprostinil. The improvement was dose related, meaning that that
those patients in the clinical trial achieving the highest doses
had the greatest improvement in exercise capacity. There is no
data about long-term effects of treprostinil. Trials with intravenous
treprostinil are still ongoing. Preliminary reports suggest that
patients starting on intravenous treprostinil (as the initial
treatment of PAH) have improved exercise capacity. Whether intravenous
treprostinil is as effective as intravenous epoprostenol is unknown.
How is treprostinil given?
The half-life of treprostinil is about four and a half hours;
although symptoms due to drug interruption can occur in less than
one hour. This means that after stopping the infusion, about half
the drug is still in the patient's system four and a half hours
later. Treprostinil is stable at room temperature for 48 hours
when mixed with sterile solution (this means it does not have
to be refrigerated).
Subcutaneous treprostinil is delivered via the Mini-Med portable
infusion pump. Each infusion site is generally used for up to
three days although some patients use the same site for a longer
period of time. Intravenous treprostinil must be administered
via a surgically placed central venous catheter. Intravenous treprostinil
is delivered via the CADD Legacy pump (the same pump that is used
for intravenous epoprostenol administration).
Dosing of treprostinil
Optimal dosing of treprostinil remains unclear. While the package
insert suggests initiating subcutaneous treprostinil at 1.25 ng/kg/min
(0.625 ng/kg/min in those with liver impairment), many patients
are started at a dose of 2.5 ng/kg/min. The dose is gradually
increased to achieve symptomatic relief. It is not uncommon for
some patients to be on a dose of approximately 70 ng/kg/min, or
more, to achieve optimal benefit with a tolerable safety profile.
Intravenous treprostinil in new patients is generally initiated
at 2.5 ng/kg/min, and also titrated up to achieve symptomatic
relief. Little information is available about dosing of intravenous
treprostinil, but preliminary studies suggest that compared to
epoprostenol, higher doses of treprostinil appear necessary to
achieve adequate effectiveness.
What are the main side effects with treprostinil?
The major side effect with subcutaneously administered treprostinil
is the development of infusion site pain (which often improves
after 6 months or longer of therapy) and/or redness at the site
of the subcutaneous infusion. This occurs in more than 80% of
patients. The occurrence of site pain does not appear to be dose-related.
Cellulitis and bleeding can also occur at the infusion site. There
are various remedies used to treat this problem, and patients
differ in their response to these remedies. The other side effects
of treprostinil are similar to those seen with epoprostenol and
include flushing, nausea, jaw pain, diarrhea, headache, extremity
pain, and skin rash. Side effects related to the intravenous use
of treprostinil, such as catheter infections, are similar to those
with intravenous epoprostenol.
How is treprostinil supplied?
Treprostinil is supplied in four concentrations (1.0 mg/ml, 2.5
mg/ml, 5.0 mg/ml, and 10.0 mg/ml), each containing 20 ml of solution
in a multidose accessible vial. A single vial should be used no
more than 14 days after the initial opening and usage of the vial,
provided that the proper storage procedures are followed.
How do patients obtain treprostinil?
Treprostinil must be prescribed by a physician and insurance approval
must be obtained prior to starting therapy. Once approved by insurance,
treprostinil is then sent directly to the hospital or clinic where
the patient is treated by either of the three specialty pharmacies:
Accredo Health Inc., Caremark, or Priority Healthcare Corporation.
Will insurance pay for treprostinil?
The cost of treprostinil is $100,000 per year or more depending
upon patient dose. Most insurance, as well as Medicaid and Medicare,
will pay for treprostinil.
Could a patient be allergic to treprostinil?
There are no reports of allergies to treprostinil. It is unlikely
that this would occur since prostacyclin is naturally made by
the body. However, any medication can cause side effects, which
are listed above. No medications are prohibited with the use of
treprostinil.
Pregnant and nursing women
Treprostinil 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.
Use in children
Treprostinil has been used in children. Clinical studies of treprostinil
did not include sufficient numbers of patients 16 years of age
and under to determine its safety and efficacy in children.
