Extended-release oral treprostinil in the management of pulmonary arterial hypertension: clinical evidence and experience.

Treprostinil diolamine is the first oral prostacyclin approved for the treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity. Clinical studies have demonstrated modest benefit as monotherapy, whereas no difference in exercise capacity was observed with combination therapy. However, these trials were limited by subtherapeutic dosing owing to intolerable adverse effects. Prostacyclin-related adverse effects, such as nausea, diarrhea, headache, flushing, and jaw pain, are prevalent. More recent pharmacokinetic and clinical studies illustrate the dose-response relationship and the importance of achieving clinically effective doses. Therefore, efforts to improve tolerability are paramount. Oral treprostinil is recommended to be administered three times daily in order to facilitate more rapid titration, higher doses achieved, and improved tolerability. Oral treprostinil has also been studied in carefully selected, stable patients that transitioned from parenteral or inhaled therapy with close monitoring for late deterioration. Ongoing clinical trials will determine the long-term effects of higher doses of oral treprostinil on clinical outcomes. This review describes the clinical evidence and practical experience with the use of oral treprostinil for PAH.