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Safety and Feasibility of Doses Greater than 54 mcg QID of Inhaled Treprostinil in Pulmonary Arterial Hypertension

Shelley Shapiro

Glenna Traiger

Nicholas Hill


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Conference: 2012 International PHA Conference and Scientific Sessions

Release Date: 06.22.2012

Presentation Type: Abstracts

Shapiro S, Traiger G, Hill W
Greater Los Angeles VA Healthcare System
David Geffen School of Medicine at UCLA, Los Angeles, CA; USA

BACKGROUND: Parenteral prostanoid therapy is efficacious in patients with Pulmonary Arterial Hypertension (PAH). The approach to patient dosing with these agents involves increasing the dose as needed to improve PAH symptoms while limiting prostanoid side effects. This results in a wide dosing range among patients. In 2009, inhaled treprostinil was approved for treatment of PAH at a dose of 54 mcg (9 breaths) QID. The inhaled treprostinil administration system provides an excess of medication in the reservoir, which allows for increased dose without increasing cost or administration burden. However, the safety, tolerability, and efficacy of titrating patients beyond the dose studied in the pivotal clinical trial to achieve treatment goals is unknown.

METHODS: This is a retrospective, non-randomized review of patients treated at a large PAH center with doses of inhaled treprostinil beyond the product labeling. Patients treated with inhaled treprostinil who were not achieving treatment goals with regard to 6 MWD, or worsening PAH symptoms, were instructed to increase to a maximum of 15-18 breaths QID as tolerated. In general, patients dose was increased by one to two breaths QID per week, and were instructed to contact the PAH center for any adverse events. Retrospective chart review of these patients was conducted to evaluate outcomes including 6MWD, Functional Class, BNP, PAH symptoms, adverse events and prostanoid side effects.

RESULTS: Thirteen NYHA FC III patients (mean age 50 years, range 30-78) with World Health Organization Group 1 PAH were evaluated; 4 patients had concomitant mild lung disease. Six patients had been transitioned from other prostanoid therapy; inhaled (4) and parenteral (3). Concomitant medications included endothelin receptor antagonist (10) and PDE-5 inhibitor (12). Median inhaled treprostinil dose at the time of evaluation was 12 breaths QID (range 10-15). Mean walk distance after approximately 3 months increased by 24 meters (range 3-72 meters) with doses beyond 9 breaths QID. BNP and functional class were unchanged. Adverse events reported included headache (1) and throat irritation (1). Follow up data at 9 to 12 months will be presented.

CONCLUSION: Preliminary results suggest patients were able to tolerate increased doses of inhaled treprostinil, and in an uncontrolled and un-blinded manner may improve. This may afford increased efficacy by dosing at a higher number of inhalations per session, without increasing cost or administration complexity. Based on these results, an open-label, prospective study to assess efficacy, safety and tolerability of high dose inhaled treprostinil should be considered.