Murali M Chakinala1, Jeremy P Feldman2, Franz Rischard3, Michael Mathier4, Meredith Broderick5, Nicole Leedom5, Kevin Laliberte5, R James White6. 1. Department of Medicine, Washington University, St. Louis, Missouri, USA. 2. Arizona Pulmonary Specialists, Ltd, Phoenix, Arizona, USA. 3. Department of Medicine, University of Arizona, Tuscon, Arizona, USA. 4. Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. 5. United Therapeutics Corporation, Research Triangle Park, North Carolina, USA. 6. Division of Pulmonary and Critical Care Medicine and the Mary M. Parkes Center, University of Rochester Medical Center, University of Rochester Medical Center, Rochester, New York, USA. Electronic address: jim_white@urmc.rochester.edu.
Abstract
BACKGROUND: Parenteral prostanoids are effective treatment for pulmonary arterial hypertension, but long-term pump infusion systems have significant delivery-related safety and convenience limitations. METHODS: Subjects with a favorable risk profile transitioned from parenteral to oral treprostinil using a protocol-driven titration during 5 days of inpatient observation. Baseline and Week 24 assessments included 6-minute walk distance, echocardiogram, right heart catheterization, pharmacokinetics, treatment satisfaction and quality of life. Thirty-three subjects (76% female, mean age 50 years) enrolled; 85% were using subcutaneous treprostinil with a median dose of 57 (range 25 to 111) ng/kg/min. Participants were using background, approved non-prostanoid therapy, including 9 on 2 oral therapies; baseline right atrial pressure and cardiac output were in the normal range. All 33 subjects transitioned to oral treprostinil therapy within 4 weeks, but 2 transitioned back to parenteral drug before Week 24. At Week 24, subjects were taking a median total daily dose of 44 (15 to 75) mg, with 25 of 31 using a 3-times-daily regimen at 7- to 9-hour intervals. RESULTS: The 6-minute walk distance was preserved (median +17 m [-98 to 95 m]) at its baseline of 446 m. Hemodynamic variables, including pulmonary vascular resistance, were similar at Week 24 except for mixed venous saturation, which dropped from a median of 71% to 68% (p < 0.001). Overall quality of life and treatment satisfaction measures did not change; however, mood-related symptom and treatment convenience subscores improved. Common adverse effects included headache, nausea, flushing and diarrhea. CONCLUSIONS: Lower risk patients managed on parenteral treprostinil may be candidates for transition to a more convenient, oral form of the drug.
BACKGROUND: Parenteral prostanoids are effective treatment for pulmonary arterial hypertension, but long-term pump infusion systems have significant delivery-related safety and convenience limitations. METHODS: Subjects with a favorable risk profile transitioned from parenteral to oral treprostinil using a protocol-driven titration during 5 days of inpatient observation. Baseline and Week 24 assessments included 6-minute walk distance, echocardiogram, right heart catheterization, pharmacokinetics, treatment satisfaction and quality of life. Thirty-three subjects (76% female, mean age 50 years) enrolled; 85% were using subcutaneous treprostinil with a median dose of 57 (range 25 to 111) ng/kg/min. Participants were using background, approved non-prostanoid therapy, including 9 on 2 oral therapies; baseline right atrial pressure and cardiac output were in the normal range. All 33 subjects transitioned to oral treprostinil therapy within 4 weeks, but 2 transitioned back to parenteral drug before Week 24. At Week 24, subjects were taking a median total daily dose of 44 (15 to 75) mg, with 25 of 31 using a 3-times-daily regimen at 7- to 9-hour intervals. RESULTS: The 6-minute walk distance was preserved (median +17 m [-98 to 95 m]) at its baseline of 446 m. Hemodynamic variables, including pulmonary vascular resistance, were similar at Week 24 except for mixed venous saturation, which dropped from a median of 71% to 68% (p < 0.001). Overall quality of life and treatment satisfaction measures did not change; however, mood-related symptom and treatment convenience subscores improved. Common adverse effects included headache, nausea, flushing and diarrhea. CONCLUSIONS: Lower risk patients managed on parenteral treprostinil may be candidates for transition to a more convenient, oral form of the drug.
Authors: James C Coons; Kristen Pogue; Andrew R Kolodziej; Glenn A Hirsch; Marjorie Patricia George Journal: Curr Cardiol Rep Date: 2019-11-22 Impact factor: 2.931
Authors: James C Coons; Karryn Crisamore; Solomon Adams; Ashley Modany; Marc A Simon; Wenchen Zhao; Imam H Shaik; Raman Venkataramanan; Philip E Empey Journal: Ther Adv Respir Dis Date: 2021 Jan-Dec Impact factor: 4.031
Authors: Franck F Rahaghi; Jeremy P Feldman; Roblee P Allen; Victor Tapson; Zeenat Safdar; Vijay P Balasubramanian; Shelley Shapiro; Michael A Mathier; Jean M Elwing; Murali M Chakinala; R James White Journal: Pulm Circ Date: 2017-03-21 Impact factor: 3.017
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