1. Background 2. Drug classes 3. Overview of prostacyclin analogues 4. Overview of treprostinil 5. Inhaled treprostinil 6. Conclusion 7. Expert opinion Drug Evaluation Inhaled treprostinil sodium for pulmonary hypertension Vedant Gupta & Richard A Krasuski † † Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA Introduction: Pulmonary arterial hypertension is an increasingly recognized heterogeneous disease with significant morbidity and mortality, requiring a multimodal approach to treatment. Inhalation administration of treprostinil sodium (Tyvaso Ò ) permits higher local drug concentration without some of the side effects of parenteral prostanoids. Areas covered: After a broad discussion centering on available prostacyclins, a thorough literature review of treprostinil is undertaken, focusing on the time- line of clinical studies, specifically highlighting the major trials that shape cur- rent indications and usage. The literature search was undertaken via multiple search engines and strategies with review of cited and associated articles to provide a comprehensive discussion on the topic. Expert opinion: While safe and well tolerated, inhaled treprostinil sodium should be limited, based on available data, to use as add-on therapy for patients with Group I pulmonary hypertension not effectively controlled on oral therapy. Despite documented safety for the conversion from inhaled ilo- prost to inhaled treprostinil, the transition of patients stable on parenteral agents to inhaled treprostinil should be cautioned due to the potential for clinical decompensation. Keywords: 6-minute walk distance, functional capacity, inhaled therapy, prostacyclin analogue, pulmonary arterial hypertension, treprostinil (sodium) Expert Opinion on Orphan Drugs [Early Online] 1. Background Pulmonary hypertension (PH) is an increasingly prevalent problem, bridging across many subspecialties of medicine. It involves a pulmonary arteriopathy (primary or secondary), which leads to elevation in pulmonary arterial pressure (PAP), and even- tually, right-sided heart failure. While the initial insult is varied, the result of many different systemic conditions, the end pathway is common with pulmonary vaso- constriction and smooth muscle proliferation. Based on prevalence of underlying disease alone, the most common forms of PH originate from problems in the left heart, including heart failure (both systolic and diastolic dysfunction) and valvular heart disease as well as from lung diseases (Dana Point Group II and III, respec- tively) [1]. Treatment in these cases should be focused on the underlying disorder and the role of adjuvant pulmonary arterial hypertension (PAH)-targeted therapy remains controversial. When the disease process is isolated to involvement of the pulmonary arterioles and has no discernible etiology, it is referred to as ‘idiopathic’ pulmonary arterial hypertension (iPAH), previously termed ‘primary’ PAH. It is now recognized that PAH related to other disorders, including congenital heart (shunt) lesions, connective tissue disease (such as scleroderma), and human immu- nodeficiency virus, behaves similarly to iPAH. As a result these disorders are now organized together with iPAH into Group I of the Dana Point PH Classification Scheme (Table 1). Nearly all prior drug trials in PH have focused on Group I patients (PAH), and this will, therefore, be the main patient population referred to in this review. Although much still remains to be learned about its pathogenesis, 10.1517/21678707.2014.885834 © 2014 Informa UK, Ltd. e-ISSN 2167-8707 1 All rights reserved: reproduction in whole or in part not permitted Expert Opinion on Orphan Drugs Downloaded from informahealthcare.com by Cleveland Clinic on 02/14/14 For personal use only.