Transition From Epoprostenol to Treprostinil Seems Safe, Study Finds
All eight patients who participated in the study successfully made the medication transition, which involved the administration of a gradually increasing dosage of treprostinil and a simultaneously decreasing dosage of epoprostenol. Four of the patients made the transition in a day or less, and the rest were weaned from epoprostenol after about 24 days.
The change in drug therapy did not appear to alter the patients' ability to endure physical activity, as measured by the New York Heart Association (NYHA) classification system. Six of the patients had been classified as NYHA class II and one as class III before making the transition to treprostinil, and each patient's classification remained unchanged afterward. The NYHA classification of the eighth patient, who was partially paralyzed before the study began, was not assessed for this project.
The study was sponsored by United Therapeutics Corp., the manufacturer of Remodulin, the treprostinil product that was approved last month by the Food and Drug Administration (FDA) for the treatment of PAH in patients with NYHA class IIIV symptoms. Results of the study appeared in the May issue of Chest.
Each patient who participated in the study had been administered epoprostenol for 4.5 to 36 months to treat severe PAH characterized by an NYHA classification of III or IV. A portable infusion pump was used to deliver the drug through a permanently implanted venous catheter. In all cases, epoprostenol had improved the patient's NYHA classification, but sepsis or another life-threatening complication occurred during the continuous intravenous therapy.
Patients began the medication transition by receiving their usual prescribed dosage of epoprostenol, supplemented by treprostinil delivered subcutaneously at no more than 5 ng of drug per kilogram of body weight per minute. The initial treprostinil dosage was no more than half of the patient's epoprostenol dosage. Treprostinil was delivered into the patients' subcutaneous abdominal tissues by a microinfusion pump.
After at least six hours of treatment, the epoprostenol dosage was gradually decreased by 2 ng/kg/minute or less and the treprostinil dosage increased by no more than 50 percent. Dosage levels for the two drugs were further adjusted until the patients were able to discontinue epoprostenol therapy. During the transition, the epoprostenol dosage was adjusted to control symptoms of prostacyclin overdosage or underdosage.
In half of the patients, small hematomas developed at the treprostinil infusion site. All of the patients reported having pain, redness, and swelling at the treprostinil infusion site. The symptoms were treated with topical cooling agents, corticosteroid or nonsteroidal antiinflammatory ointments, oral analgesics, and oral prednisolone.
Seven of the patients reported that their infusion-site pain was moderate to severe at first, but six said that their pain had "markedly improved" within a few weeks after starting treprostinil therapy. The research team reported that the clinical condition of all but one of the study participants remained unchanged after four to 11 months of follow-up.
United Therapeutics announced last month that FDA has asked the company to conduct a randomized, placebo-controlled study to investigate whether patients can move from epoprostenol therapy to treprostinil treatment without their clinical status necessitating a return to epoprostenol.