Room Temperature Stable Epoprostenol (Veletri^®)

Treatment for Pulmonary Hypertension

Issued by PHA's Scientific Leadership Council
Last Updated December 2010

 

What is Room Temperature Stable Epoprostenol (Veletri^®)?

Room temperature stable epoprostenol (Veletri^®) 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 2010 for the treatment of New York Heart Association Class III or IV symptoms in patients who have primary pulmonary hypertension or pulmonary hypertension associated with scleroderma who do not respond adequately to conventional therapy. The term “primary pulmonary hypertension” is no longer utilized by pulmonary hypertension experts, and so from a practice perspective RTS epoprostenol is being utilized in patients with World Health Organization group I PAH who have NYHA Class III or IV symptoms.

How does RTS epoprostenol (Veletri^®) work?

RTS 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). RTS epoprostenol (Veletri^®) works in a way that is believed to be identical to epoprostenol sodium (Flolan^®), but is more stable at room temperature.

How is RTS epoprostenol (Veletri^®) given?

RTS 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 (for example, the CADD Legacy pump) is used to deliver the drug.

The stability properties of RTS Epoprostenol (Veletri^®) may provide a measure of storage and administration convenience that distinguishes it from epoprostenol sodium (Flolan^®).

Patients can now change cassettes every 24 hours when Veletri^® is prepared as directed and used immediately after reconstitution and dilution at concentrations ≥ 6,000 ng/mL without ice packs.

At concentrations ≥ 30,000 ng/mL, RTS epoprostenol, when reconstituted and immediately diluted in the cassette, can be stored at 36°F to 46°F (2°C to 8°C) for up to 7 days and then administered at room temperature (77°F) for up to 24 hours. Accordingly patients utilizing drug concentrations ≥ 30,000 ng/mL can now prepare up to 7 days' worth of medication in advance and store fully diluted cassettes in the refrigerator.

How is RTS epoprostenol (Veletri^®) dosed?

RTS Epoprostenol is dosed according to a patient's body weight, in kilograms (kg). The per nanogram potency of RTS Epoprostenol is believed to be the same as that of epoprostenol sodium (Flolan^®). Accordingly when a patient is switched from epoprostenol sodium to RTS epoprostenol (Veletri^®) the standard procedure is to switch to the same dose. Anecdotal reports of patients who have experienced greater prostanoid type side effects when switched from Flolan^® to Veletri^® suggest that in some patients the effective dose of Flolan^® they had been receiving may have been lower than thought due to deterioration of Flolan^® during the course of its infusion. The starting dose of RTS epoprostenol 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 RTS epoprostenol (Veletri^®)?

RTS epoprostenol is stable only when reconstituted and diluted as directed using Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP. It must not be reconstituted or diluted with Flolan^® diluent. RTS Epoprostenol must not be reconstituted or mixed with any other parenteral medications or solutions prior to or during administration. Do not freeze reconstituted solutions of RTS Epoprostenol. Discard any reconstituted solution that has been frozen, refrigerated for more than 5 days, or held at room temperature (77°F/25°C) for more than 48 hours. Do not expose RTS Epoprostenol solution to direct sunlight. Each vial is for single use only; discard any unused solution.

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.

As of December 2010 when this summary was produced, the extent of clinical experience with RTS Epoprostenol (Veletri^®) with regard to transition from epoprostenol sodium (Flolan^®) and with regard to mixing and refrigerator storage of multiple cassettes for several days is limited. A registry (PROSPECT) is gathering additional information about clinical experience with RTS Epoprostenol at this time.

What are the frequent side effects of RTS epoprostenol (Veletri^®)?

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 RTS epoprostenol (Veletri^®) supplied?

RTS Epoprostenol is supplied as a powder; 1.5 mg (1,5000,000 ng) in a vial . RTS Epoprostenol is then dissolved in Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP. It must not be reconstituted or diluted with Flolan^® diluent.

How do patients obtain RTS epoprostenol (Veletri^®)?

RTS 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 the specialty pharmacy Accredo Health Inc.

Will insurance pay for RTS epoprostenol (Veletri^®)?

Most insurance, as well as Medicaid and Medicare, will pay for RTS epoprostenol.

Could a patient be allergic to RTS epoprostenol (Veletri^®)?

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:

Experience with RTS Epoprostenol in children is limited at this time. However, it is anticipated that it should be as safe as epoprostenol sodium.

Pregnant and nursing women:

RTS 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.