For US Physicians Only
PAH Overview
About PAH Importance of prostacyclin therapy Prostacyclin Analogues
About Orenitram
Overview Pharmacologic actions
Efficacy and Safety
Improvement in 6MWD Adverse reactions Open-label extension study AE management strategies Open-label Transition Study
Dosing
Dosage and administration BID/TID pharmacokinetics Ability to Dose Progressively Dose conversion
Access and Support
Support for your practice Starting a patient Resources Referral Portal Request a Rep
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For PAH, a progressive disease, Orenitram offers the ability to dose progressively

Patients on Orenitram achieved similar exposure to Remodulin (treprostinil) Injection1,2

*The shaded area was approximated based on the mean ± SD across all time points.

Data represent mean treprostinil concentrations of patients who received Orenitram TID only.2

Study design: Pharmacokinetic (PK) comparison was based on mean treprostinil concentration vs. time plots by treatment regimen in the 24-week, multicenter, open-label transition study. Thirty-three WHO Group 1 patients on stable doses of IV/SC treprostinil as well as background therapy with a PDE-5i and/or ERA were enrolled. Patients were WHO FC I or II and hemodynamically stable at baseline, with a cardiac index >2.2 L/m2, RAP<11 mm Hg, and PVR<10 Wood units. The primary endpoint of the study was the safety and tolerability of the transition.1,2

Safety

In clinical studies, Orenitram demonstrated the ability to gradually titrate dose up or down to tolerability and clinical response

Dosing

Total daily dose.

§TID cohort includes dosing and pharmacokinetic data from 1 patient who discontinued the study prior to week 24 but completed pharmacokinetic assessments prior to discontinuation.

AUC=area under the curve; ERA=endothelin receptor antagonist; FC=functional class; IV=intravenous; PAH=pulmonary arterial hypertension; PDE-5i=phosphodiesterase type 5 inhibitor; PVR=pulmonary vascular resistance; RAP=right arterial pressure; SC=subcutaneous; SD=standard deviation; TID=3 times daily; WHO=World Health Organization.

SELECTED IMPORTANT SAFETY INFORMATION FOR ORENITRAM

Please see below for the complete Important Safety Information for Orenitram and click here for the Full Prescribing Information for Orenitram.

SELECTED IMPORTANT SAFETY INFORMATION FOR REMODULIN

Please see below for the complete Important Safety Information for Remodulin and click here for the Full Prescribing Information for Remodulin.

NEXT: Review instructions for transitioning from parenteral treprostinil to Orenitram.

Important Safety Information for Orenitram

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

DRUG INTERACTIONS / SPECIFIC POPULATIONS

ADVERSE REACTIONS

Indication

Orenitram is a prostacyclin vasodilator indicated for treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity.

The study that established effectiveness included predominately patients with WHO functional class II-III symptoms and etiologies of idiopathic or heritable PAH (75%) or PAH associated with connective tissue disease (19%). When used as the sole vasodilator, the effect of Orenitram on exercise is about 10% of the deficit, and the effect, if any, on a background of another vasodilator is probably less than this.

OREISIhcpJAN16

Please see the Full Prescribing Information and Patient Information for Orenitram.

For additional information about Orenitram, call 1-877-UNITHER (1-877-864-8437).

Important Safety Information for Remodulin

WARNINGS AND PRECAUTIONS
  • Chronic intravenous (IV) infusions of Remodulin are delivered using an indwelling central venous catheter. This route is associated with the risk of blood stream infections (BSI) and sepsis, which may be fatal. Therefore, continuous subcutaneous (SC) infusion is the preferred mode of administration
  • Avoid abrupt withdrawal or sudden large reductions in dosage of Remodulin, which may result in worsening of PAH symptoms
  • Titrate slowly in patients with hepatic or renal insufficiency because such patients will likely be exposed to greater systemic concentrations relative to patients with normal hepatic or renal function
  • Remodulin dosage adjustment may be necessary if inhibitors or inducers of CYP2C8 are added or withdrawn. Co-administration of Remodulin with a CYP2C8 inhibitor increases exposure to treprostinil, or with an inducer, decreases exposure to treprostinil
DRUG INTERACTIONS/SPECIFIC POPULATIONS
  • Remodulin is a potent pulmonary and systemic vasodilator. Concomitant administration of Remodulin with blood pressure lowering agents, such as diuretics, antihypertensive agents, or other vasodilators, may increase the risk of symptomatic hypotension
  • Since Remodulin inhibits platelet aggregation, there may be an increased risk of bleeding, particularly among patients receiving anticoagulants
  • Safety and effectiveness of Remodulin in pediatric patients have not been established. It is unknown if geriatric patients respond differently than younger patients. Caution should be used when selecting a dose for geriatric patients
  • There are no adequate and well-controlled studies with Remodulin in pregnant women. It is not known whether treprostinil is excreted in human milk
ADVERSE REACTIONS
  • In clinical studies of SC Remodulin infusion, the most common adverse events reported were infusion site pain and infusion site reaction (redness and swelling). These symptoms were often severe and sometimes required treatment with narcotics or discontinuation of Remodulin. The IV infusion of Remodulin has been associated with a risk of blood stream infections, arm swelling, paresthesias, hematoma, and pain. Other common adverse events (≥3% more than placebo) seen with either SC or IV Remodulin were headache, diarrhea, nausea, jaw pain, vasodilatation, and edema

Indication

Remodulin is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise. Studies establishing effectiveness included patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (58%), PAH associated with congenital systemic-to-pulmonary shunts (23%), or PAH associated with connective tissue diseases (19%). It may be administered as a continuous subcutaneous infusion or continuous intravenous infusion; however, because of the risks associated with chronic indwelling central venous catheters, including serious blood stream infections, continuous intravenous infusion should be reserved for patients who are intolerant of the subcutaneous route or in whom these risks are considered warranted.

In patients with PAH requiring transition from Flolan® (epoprostenol sodium), Remodulin is indicated to diminish the rate of clinical deterioration. The risks and benefits of each drug should be carefully considered prior to transition.

Please see the Full Prescribing Information for Remodulin.

For additional information, visit Remodulin.com or call 1-877-UNITHER (1-877-864-8437).

Reference: 1. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2016.

References: 1. Archer SL, Marsboom G, Kim GH, et al. Epigenetic attenuation of mitochondrial superoxide dismutase 2 in pulmonary arterial hypertension: a basis for excessive cell proliferation and a new therapeutic target. Circulation. 2010;121(24):2661-2671. 2. McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009;53(17):1573-1619. 3. Clapp LH, Gurung R. The mechanistic basis of prostacyclin and its stable analogues in pulmonary arterial hypertension: role of membrane versus nuclear receptors. Prostaglandins Other Lipid Mediat. 2015;120:56-71. 4. Barst RJ, Galiè N, Naeije R, et al. Long-term outcome in pulmonary arterial hypertension patients treated with subcutaneous treprostinil. Eur Respir J. 2006;28(6):1195-1203. 5. Lang I, Gomez-Sanchez M, Kneussl M, et al. Efficacy of long-term subcutaneous treprostinil sodium therapy in pulmonary hypertension. Chest. 2006;129(6):1636-1643. 6. Sadushi-Koliçi R, Skoro-Sajer N, Zimmer D, et al. Long-term treatment, tolerability, and survival with sub-cutaneous treprostinil for severe pulmonary hypertension. J Heart Lung Transplant. 2012;31(7):735-743. 7. Sitbon O, Humbert M, Nunes H, et al. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J Am Coll Cardiol. 2002;40(4):780-788. 8. Champion HC, Michelakis ED, Hassoun PM. Comprehensive invasive and noninvasive approach to the right ventricle–pulmonary circulation unit: state of the art and clinical and research implications. Circulation. 2009;120(11):992-1007. 9. Michelakis ED, Wilkins MR, Rabinovitch M. Emerging concepts and translational priorities in pulmonary arterial hypertension. Circulation. 2008;118(14):1486-1495. 10. Schiebler ML, Bhalla S, Runo J, et al. Magnetic resonance and computed tomography imaging of the structural and functional changes of pulmonary arterial hypertension. J Thorac Imaging. 2013;28(3):178-193. 11. Bogaard HJ, Abe K, Vonk Noordegraaf A, Voelkel NF. The right ventricle under pressure: cellular and molecular mechanisms of right-heart failure in pulmonary hypertension. Chest. 2009;135(3):794-804. 12. Barst R. How has epoprostenol changed the outcome for patients with pulmonary arterial hypertension? lnt J Clin Pract. 2010;64(suppl 168):23-32. 13. Badano LP, Ginghina C, Easaw J, et al. Right ventricle in pulmonary arterial hypertension: haemodynamics, structural changes, imaging, and proposal of a study protocol aimed to assess remodelling and treatment effects. Eur J Echocardiogr. 2010;11(1):27-37. 14. Voelkel NF, Quaife RA, Leinwand LA, et al. Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation. 2006;114(17):1883-1891. 15. Tonelli AR, Arelli V, Minai OA, et al. Causes and circumstances of death in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2013;188(3):365-369. 16. Galiè N, Torbicki A, Barst R, et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension: the Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J. 2004;25(24):2243-2278. 17. Hoeper MM, Bogaard HJ, Condliffe R, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 suppl D):D42-D50. 18. Elliot CA, Kiely DG. Pulmonary hypertension. Contin Educ Anaesth Crit Care Pain. 2006;6(1):17-22. 19. Palevsky HI. The early diagnosis of pulmonary arterial hypertension: can we do better? Chest. 2011;140(1):4-6. 20. Brown LM, Chen H, Halpern S, et al. Delay in recognition of pulmonary arterial hypertension: factors identified from the REVEAL Registry. Chest. 2011;140(1):19-26. 21. Badesch DB, Raskob GE, Elliott CG, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. 2010;137(2):376-387. 22. Taichman DB, Ornelas J, Chung L, et al. Pharmacologic therapy for pulmonary arterial hypertension in adults: CHEST Guideline and Expert Panel Report. Chest. 2014;146(2):449-475. 23. Frost AE, Badesch DB, Barst RJ, et al. The changing picture of patients with pulmonary arterial hypertension in the United States: how REVEAL differs from historic and non-US contemporary registries. Chest. 2011;139(1):128-137. 24. Humbert M, Sitbon O, Chaouat A, et al. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med. 2006;173(9):1023-1030. 25. Peacock AJ, Murphy NF, McMurray JJ, Caballero L, Stewart S. An epidemiological study of pulmonary arterial hypertension. Eur Respir J. 2007;30(1):104-109. 26. Huertas A, Phan C, Bordenave J, et al. Regulatory T cell dysfunction in idiopathic, heritable and connective tissue-associated pulmonary arterial hypertension. Chest. 2016. doi: 10.1016/j.chest.2016.01.004.

References: 1. Jing Z-C, Parikh K, Pulido T, et al. Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension:
a randomized, controlled trial. Circulation. 2013;127(5):624-633. 2. McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009;53(17):1573-1619. 3. Gomberg-Maitland M, Olschewski H. Prostacyclin therapies for the treatment of pulmonary arterial hypertension. Eur Respir J. 2008;31(4):891-901. 4. Tuder RM, Cool CD, Geraci MW, et al. Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med. 1999;159(6):1925-1932. 5. McLaughlin VV, McGoon MD. Pulmonary arterial hypertension. Circulation. 2006;114(13):1417-1431. 6. Badesch DB, Raskob GE, Elliott CG, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. 2010;137(2):376-387.

References: 1. McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009;53(17):1573-1619. 2. Humbert M, Ghofrani HA. The molecular targets of approved treatments for pulmonary arterial hypertension. Thorax. 2016;71(1):73-83. 3. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2016. 4. Nicolaou KC, Barnette WE, Magolda RL. Synthesis and biological properties of prostacyclins and prostaglandin endoperoxide analogs. In: Roberts SM, Scheinmann F, eds. Chemistry, Biochemistry & Pharmacological Activity of Prostanoids. Elmsford, NY: Pergamon Press; 1978. 5. Christie WW. Introduction–Structures and key enzymes. American Oil Chemists' Society website. www.lipidlibrary.aocs.org. Updated May 2014. Accessed February 23, 2016. 6. Whittle BJ, Silverstein AM, Mottola DM, Clapp LH. Binding and activity of the prostacyclin receptor (IP) agonists, treprostinil and iloprost, at human prostanoid receptors: treprostinil is a potent DP1 and EP2 agonist. Biochem Pharmacol. 2012;84(1):68-75. 7. Falcetti E, Hall SM, Phillips PG, et al. Smooth muscle proliferation and role of the prostacyclin (IP) receptor in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med. 2010;182(9):1161-1170. 8. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004;351(14):1425-1436. 9. Clapp LH, Gurung R. The mechanistic basis of prostacyclin and its stable analogues in pulmonary arterial hypertension: role of membrane versus nuclear receptors. Prostaglandins Other Lipid Mediat. 2015;120:56-71.

References: 1. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2016. 2. Jing Z-C, Parikh K, Pulido T, et al. Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension: a randomized, controlled trial. Circulation. 2013;127(5):624-633.

Reference: 1. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2016.

References: 1. Jing Z-C, Parikh K, Pulido T, et al. Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension: a randomized, controlled trial. Circulation. 2013;127(5):624-633. 2. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2016.

Reference: 1. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2016.

References: 1. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2016. 2. Data on file. United Therapeutics Corporation. Research Triangle Park, NC. September 2012.

References: 1. McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009;53(17):1573-1619. 2. Rahaghi FF, Feldman JP, Allen RP, et al. The Delphi process in the creation of a consensus statement for practical use of Orenitram. Poster presented at: American Thoracic Society (ATS) 2015 International Conference; May 15-20, 2015; Denver, CO. 3. Hasson F, Keeney S, McKenna H. Research guidelines for the Delphi survey technique. J Adv Nurs. 2000;32(4):1008-1015. 4. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2016.

References: 1. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2016. 2. Data on file. United Therapeutics Corporation. Research Triangle Park, NC. October 2015.

Reference: 1. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2016.

References: 1. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2016. 2. Data on file. United Therapeutics Corporation. Research Triangle Park, NC. March 2016.

References: 1. Data on file. United Therapeutics Corporation. Research Triangle Park, NC. October 2015. 2. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2016.

Reference: 1. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2016.

Reference: 1. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2016.

The information contained in this section of the site is clinical in nature and specifically created for healthcare professionals.

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Important Safety Information for Orenitram

Important Safety Information for Orenitram

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

DRUG INTERACTIONS / SPECIFIC POPULATIONS

ADVERSE REACTIONS

Indication

Orenitram is a prostacyclin vasodilator indicated for treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity.

The study that established effectiveness included predominately patients with WHO functional class II-III symptoms and etiologies of idiopathic or heritable PAH (75%) or PAH associated with connective tissue disease (19%). When used as the sole vasodilator, the effect of Orenitram on exercise is about 10% of the deficit, and the effect, if any, on a background of another vasodilator is probably less than this.

OREISIhcpJAN16

Please see the Full Prescribing Information and Patient Information for Orenitram.

For additional information about Orenitram, call 1-877-UNITHER (1-877-864-8437).

Important Safety Information for Remodulin

WARNINGS AND PRECAUTIONS
  • Chronic intravenous (IV) infusions of Remodulin are delivered using an indwelling central venous catheter. This route is associated with the risk of blood stream infections (BSI) and sepsis, which may be fatal. Therefore, continuous subcutaneous (SC) infusion is the preferred mode of administration
  • Avoid abrupt withdrawal or sudden large reductions in dosage of Remodulin, which may result in worsening of PAH symptoms
  • Titrate slowly in patients with hepatic or renal insufficiency because such patients will likely be exposed to greater systemic concentrations relative to patients with normal hepatic or renal function
  • Remodulin dosage adjustment may be necessary if inhibitors or inducers of CYP2C8 are added or withdrawn. Co-administration of Remodulin with a CYP2C8 inhibitor increases exposure to treprostinil, or with an inducer, decreases exposure to treprostinil
DRUG INTERACTIONS/SPECIFIC POPULATIONS
  • Remodulin is a potent pulmonary and systemic vasodilator. Concomitant administration of Remodulin with blood pressure lowering agents, such as diuretics, antihypertensive agents, or other vasodilators, may increase the risk of symptomatic hypotension
  • Since Remodulin inhibits platelet aggregation, there may be an increased risk of bleeding, particularly among patients receiving anticoagulants
  • Safety and effectiveness of Remodulin in pediatric patients have not been established. It is unknown if geriatric patients respond differently than younger patients. Caution should be used when selecting a dose for geriatric patients
  • There are no adequate and well-controlled studies with Remodulin in pregnant women. It is not known whether treprostinil is excreted in human milk
ADVERSE REACTIONS
  • In clinical studies of SC Remodulin infusion, the most common adverse events reported were infusion site pain and infusion site reaction (redness and swelling). These symptoms were often severe and sometimes required treatment with narcotics or discontinuation of Remodulin. The IV infusion of Remodulin has been associated with a risk of blood stream infections, arm swelling, paresthesias, hematoma, and pain. Other common adverse events (≥3% more than placebo) seen with either SC or IV Remodulin were headache, diarrhea, nausea, jaw pain, vasodilatation, and edema

Indication

Remodulin is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise. Studies establishing effectiveness included patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (58%), PAH associated with congenital systemic-to-pulmonary shunts (23%), or PAH associated with connective tissue diseases (19%). It may be administered as a continuous subcutaneous infusion or continuous intravenous infusion; however, because of the risks associated with chronic indwelling central venous catheters, including serious blood stream infections, continuous intravenous infusion should be reserved for patients who are intolerant of the subcutaneous route or in whom these risks are considered warranted.

In patients with PAH requiring transition from Flolan® (epoprostenol sodium), Remodulin is indicated to diminish the rate of clinical deterioration. The risks and benefits of each drug should be carefully considered prior to transition.

Please see the Full Prescribing Information for Remodulin.

For additional information, visit Remodulin.com or call 1-877-UNITHER (1-877-864-8437).