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Medical > Therapy > Specific treatments

Prostanoids
Continuous subcutaneous treprostinil

Treprostinil is a stable tricyclic benzidine analogue of prostacyclin which shares pharmacological actions similar to epoprostenol with similar acute hemodynamic effects. However, in contrast to epoprostenol, treprostinil is chemically stable at room temperature and has a longer half life of 3-4 hours permitting continuous subcutaneous infusion rather than continuous intravenous infusion thus avoiding the risk of severe infection and thrombosis. In a large prospective randomized placebo-controlled trial continuous subcutaneous treprostinil infused by a micro infusion pump at the initial dose of 1.25 ng/kg/min increased over the 12-week study period to a maximum allowable dose of 22 ng/kg/min was compared with placebo infusions (Simonneau et al. 2002). Besides IPAH (60 %) and PAH due to connective tissue disease (20 %) the study included also patients with Eisenmenger syndrome (20 %). The primary endpoint was a small but significant increase in the 6-minute walking distance of 16 m between the two groups. More severely ill patients who walked less than 150 m at base line had a greater treatment effect of +51 m. Concomitantly, treprostinil significantly improved dyspnea score, quality of life and hemodynamic parameters. The major side effect was pain at the infusion site in 85% of the patients leading to discontinuation of treatment in 8 % of patients in the active treatment group. Moreover, this local side effect resulted in the inability to administer higher dosis of treprostinil, so that less than half of the maximum allowable dose could be reached. A subgroup analysis showed that patients who could sustain more than 14 ng/kg/min had a median increase in the 6-minute walking distance of 36 m, whereas patients receiving less than 8 ng/kg/minute did not improve their exercise capacity.

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