u-62840 and Thromboembolism

Treprostinil is a stable, long-acting prostacyclin analogue which can be administered as a continuous subcutaneous infusion using a portable miniature delivery system. Subcutaneous treprostinil has been shown in a large multicenter randomized controlled trial to improve exercise capacity, clinical state, functional class, pulmonary hemodynamics, and quality of life in patients with pulmonary arterial hypertension, an uncommon disease of poor prognosis. Side effects include facial flush, headache, jaw pain, abdominal cramping, and diarrhea, all typical of prostacyclin, and manageable by symptom-directed dose adjustments, and infusion site pain which may make further treatment impossible in 7%-10% of the patients. Long-term survival in pulmonary arterial hypertension patients treated with subcutaneous treprostinil is similar to that reported with intravenous epoprostenol. There are uncontrolled data suggesting efficacy of subcutaneous treprostinil in chronic thromboembolic pulmonary hypertension. Treprostinil can also be administered intravenously, although increased doses, up to 2-3 times those given subcutaneously, appear to be needed to obtain the same efficacy. Preliminary results of a randomized controlled trial of inhaled treprostinil on top of bosentan and sildenafil therapies have shown significance on the primary endpoint, which was exercise capacity as assessed by the distance walked in 6 minutes. Trials of oral formulations of treprostinil have been initiated.

Topics: Administration, Cutaneous; Antihypertensive Agents; Chronic Disease; Epoprostenol; Exercise Test; Exercise Tolerance; Humans; Hypertension, Pulmonary; Thromboembolism

Chronic thromboembolic pulmonary hypertension (CTEPH) results from non-resolving pulmonary thromboemboli that are resistant to plasmatic anticoagulation. Because of a secondary pulmonary arteriopathy accompanying major vessel obstruction, the disorder may be a target for vasodilator therapy.. In an open-label uncontrolled study, we investigated the prostacyclin analog treprostinil given s.c. in patients with severe inoperable CTEPH.. Between September 1999 and September 2005, 25 patients were included if their World Health Organization (WHO) functional class was III or IV, if their six-minute walking distance (6-MWD)

Topics: Aged; Antihypertensive Agents; Cardiac Output; Case-Control Studies; Chronic Disease; Epoprostenol; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Infusion Pumps; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Pain; Pain Measurement; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prospective Studies; Pulmonary Embolism; Risk Assessment; Severity of Illness Index; Thromboembolism; Time Factors; Treatment Outcome; Vascular Resistance; Vasodilator Agents; Walking

Prostacyclin analogs are Food and Drug Administration-approved therapies for the treatment of pulmonary arterial hypertension and can be administered by inhalational, intravenous (IV), or subcutaneous (SQ) routes. Because there are limited data to guide the transition between SQ to IV prostacyclin analogs, we describe our experience.. We performed a retrospective review of patients with pulmonary hypertension diagnosed by right heart catheterization, who underwent transition from SQ to IV prostacyclin analogs.. We included 7 patients with pulmonary arterial hypertension and 2 with chronic thromboembolic pulmonary hypertension in this retrospective study. Median (interquartile range) age was 54 (39-63) years, and 67% were women. The reasons for the SQ to IV switch were site pain (n = 6, 67%), major surgery (n = 2, 22%), and septic shock (n = 1, 11%). SQ treprostinil was converted to IV treprostinil (n = 5, 56%) or IV epoprostenol (n = 4, 44%). When SQ treprostinil was converted to IV treprostinil, the initial mean (range) dose decreased from 84.9 (36.5-167) to 70.8 (24-114) ng·kg⁻¹·min⁻¹. When SQ treprostinil was converted to IV epoprostenol, the dose decreased from 24.5 (17.5-30) to 13.3 (9-20) ng·kg⁻¹·min⁻¹. The patient transitioned from SQ to IV treprostinil in the context of septic shock died a month after hospitalization. No deteriorations were observed in the remaining patients during the first year.. Under careful monitoring, SQ treprostinil was transitioned to IV treprostinil or epoprostenol without complications. Dosing downadjustment was needed in some patients who were switched over from SQ to IV prostacyclin analogs.

Topics: Adult; Antihypertensive Agents; Epoprostenol; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Injections, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Retrospective Studies; Shock, Septic; Thromboembolism