Remodulin (treprostinil)

Remodulin (treprostinil sodium) injection is a continuous subcutaneous infusion for the treatment of pulmonary arterial hypertension (PAH) in patients with NYHA Class II-IV symptoms. Remodulin is intended to diminish the symptoms, such as shortness of breath, associated with physical activity in PAH patients.

Remodulin is supplied in concentrations of 1.0 mg/mL, 2.5 mg/mL, 5.0 mg/mL and 10.0 mg/mL. The standard infusion rate is 1.25 ng/kg/min, but can be reduced in the event that the original dose cannot be tolerated.

Pulmonary arterial hypertension (PAH) is a disease in which blood pressure is abnormally high in the arteries between the heart and lungs. PAH is characterized by symptoms of shortness of breath during physical exertion. The condition can ultimately lead to heart failure.

Two 12-week, multicenter, randomized, double-blind studies were conducted to compare Remodulin to placebo. A total of 470 subjects with NYHA Class II-IV pulmonary arterial hypertension (PAH) we enrolled in the studies. The baseline measures were 6-minute walking distance and level of shortness of breath during this physical test (Borg dyspnea score). The primary endpoint was change in 6-minute walking distance over the 12-week treatment period. There was a noteworthy change in 6-minute walking distance for those subjects treated with Remodulin, although the effects did not achieve conventional levels of statistical significance. There was a statistically significant change in subjects' Borg dyspnea scores with the Remodulin treatment. There were significant differences between Remodulin- and placebo-treated subjects in eight out of ten hemodynamic parameters that were evaluated, including cardiac index; mean pulmonary arterial pressure; pulmonary vascular resistance indexed; mean right atrial pressure; systemic vascular resistance indexed; mixed venous oxygen saturation. The two hemodynamic parameters that did not achieve statistical significance were mean systemic arterial pressure and heart rate.

At the time of FDA approval, clinical studies of Remodulin were still ongoing for the PAH indication to explore further effects and potential benefits of the drug. In addition, a post-marketing, phase IV clinical trial is expected to commence.

In clinical trials, infusion site pain and infusion site reaction were the most frequently reported adverse events. Both of these effects were experienced by over 80% subjects receiving Remodulin therapy.

The following adverse events were also reported in clinical trials:

• Headache
• Diarrhea
• Nausea
• Rash
• Jaw pain
• Vasodilatation
• Dizziness
• Edema
• Pruritus (itching)
• Hypotension

The major pharmacological actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation. (From prescribing information)

For additional information about Remodulin, please visit the United Therapeutics web site at www.unither.com.