SESSION TITLE: Medical Student/Resident Pulmonary Vascular Disease 1 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Multiple therapies are available for WHO group I pulmonary arterial hypertension (PAH), including a number of medications targeting the prostacyclin pathway. Until recently these agents were only available parenterally (continuous intravenous (IV) or inhaled) [1, 2]. Selexipag is a novel oral (PO) agent FDA approved in 2015, and targets the prostacyclin IP receptor. However, lack of comparative bioavailability and pharmacokinetic data between selexipag and continuous IV prostacyclin therapy creates uncertainty in therapy transition. CASE PRESENTATION: We present a 31 year-old female who was admitted for elective transition from IV epoprostenol to PO selexipag. She was diagnosed 6 months prior with idiopathic PAH by diagnostic right heart catheterization (RHC), and had functional class 4 symptoms. Her symptoms, walk distance and estimated PA systolic pressure (PASP) by echocardiogram improved significantly on epoprostenol monotherapy and she was on a stable dose of 24 ng/kg/min for several months. RHC on transition day showed a mean pulmonary artery pressure 23 mm Hg and cardiac output 6.1 L/min. Incremental up dosing of selexipag occurred every 12 hours. Dose decreases of epoprostenol occurred every 12 hours, 3 hours after selexipag ingestion. Hourly non-invasive hemodynamic and symptom assessment was performed to determine if dosing adjustment was needed. Transition was completed by 39 hours to a selexipag dose of 1000 mcg, which she tolerated well with only mild flushing and headache. She was discharged on 1000 mcg twice daily (BID) and up titrated weekly by 200 mcg BID to final dose of 1600 mcg BID. At 1- and 2- month outpatient follow-up visits her walk distance, symptoms, and estimated PASP by echocardiogram were stable. DISCUSSION: The phase 3 GRIPHON trial leading to FDA approval protocoled up-titration of selexipag over 12 weeks in subjects not on background prostacyclin therapy [3]. Rapidity of dose increase and maximum dosing was limited by typical prostacyclin side effects. We hypothesized our patient would tolerate a more rapid up-titration of selexipag because she was already on prostacyclin therapy with epoprostenol. We estimated the dose conversion of selexipag 200 mcg BID = epoprostenol 3-4 ng/kg/min, making this patient’s final dose estimate 1200-1600 mcg BID. We dosed conservatively to an inpatient dose of 1000 mcg BID with further dose increases at usual 2 week intervals. CONCLUSIONS: To our knowledge, this is the first case of rapid transition from chronic IV epoprostenol to PO selexipag. Rapid transition was achieved with excellent symptom tolerance and without apparent adverse physiologic consequences. In addition, this patient had stable PAH symptoms, walk distance and PASP by echocardiogram at 2-month follow-up. This case suggests that a prolonged transition schedule may not be necessary when starting selexipag for patients already on established prostacyclin therapy. Reference #1: Taichman DB, Ornelas J, Chung L, Klinger JR, Lewis S, Mandel J, Palevsky HI, Rich S, Sood N, Rosenzweig EB, Trow TK, Yung R, Elliott CG, Badesch DB. Pharmacologic therapy for pulmonary arterial hypertension in adults: CHEST guideline and expert panel report. Chest. 2014;146(2):449 Reference #2: Barst RJ, Rubin LJ, Long WA, McGoon MD, Rich S, Badesch DB, Groves BM, Tapson VF, Bourge RC, Brundage BH, Koerner SK, Langleben D, Keller CA, Murali S, Uretsky BF, Clayton LM, Jöbsis MM, Blackburn SD, Shortino D, Crow JW; Primary Pulmonary Hypertension Study Group. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med 1996;334:296-301 Reference #3: Sitbon O, Channick R, Chin KM, Frey A, Gaine S, Galiè N, Ghofrani HA, Hoeper MM, Lang IM, Preiss R, Rubin LJ, Di Scala L, Tapson V, Adzerikho I, Liu J, Moiseeva O, Zeng X, Simonneau G, McLaughlin VV; GRIPHON Investigators. Selexipag for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med 2015;373:2522-2533 DISCLOSURES: Speaker/Speaker's Bureau relationship with Actelion Please note: $1001 - $5000 Added 03/05/2018 by Johnell Diwan, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Bayer Please note: $5001 - $20000 Added 03/05/2018 by Johnell Diwan, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with United Therapeutics Please note: $1001 - $5000 Added 03/05/2018 by Johnell Diwan, source=Web Response, value=Honoraria No relevant relationships by Jeremy Kim, source=Web Response No relevant relationships by Catherine Markin, source=Web Response no disclosure on file for Eduardo Serpa