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Mechanism of Action

Orenitram Is the Only Oral Prostacyclin Mimetic for PAH1

Orenitram MOA

Orenitram has a Multi-Modal Mechanism to Target the Changes That Occur in PAH1,2

Vessel Affected by PAH

  1. Vasodilation

    Directly dilates pulmonary and systemic arterial vascular beds

  2. Antiplatelet

    Inhibition of antiplatelet aggregation

  3. Antiproliferation

    Inhibition of smooth muscle cell proliferation

Orenitram oral prostacyclin mechanism of action

As a Prostacyclin Mimetic, Treprostinil Acts on Multiple Receptors3-5

Prostacyclin mimetics are synthetic drugs designed to supplement the endogenous prostacyclin that patients with PAH may be lacking.6,7

Treprostinil acts on multiple receptors: the prostacyclin receptor (IP), the prostaglandin D2 receptor 1 (DP1), the prostaglandin E2 receptor 2 (EP2) and the peroxisome proliferator-activated receptor (PPAR) - mobile

Prostacyclin Is Important for Normal Lung Function7

Naturally produced prostacyclin is a potent vasodilator that has antithrombotic and antiproliferative properties.3 Patients with PAH may have a prostacyclin deficiency in their lungs.7,8

Prostacyclin Synthase Expression in Pulmonary Arteries7*
Mobile version of chart showing the potential lack of prostacyclin in patients with PAH

* Prostacyclin synthase expression was evaluated in pulmonary artery tissue obtained from patients with PAH (n=12) and patients without PAH (n=7).⁷

Prostacyclin Is One of the 3 Established Pathways in PAH2,3,9,10

Targeting multiple pathogenic pathways is now standard of care.10

Prostacyclin
pathway3
Endothelin pathway3
Nitric oxide pathway3
Activin pathway10

Established Clinical Efficacy

Learn how Orenitram may provide clinical improvement for patients who need it.

Adverse Effects

See the most common adverse effects associated with Orenitram.

Orenitram Patient Profiles

See profiles of patients who may benefit from timely clinical intervention with Orenitram.

AE=adverse effect; cAMP=cyclic adenosine monophosphate; DP1=D-type prostanoid 1; EP2=prostaglandin E2; IP=prostaglandin I2; MOA=mechanism of action; PAH=pulmonary arterial hypertension; PPAR=peroxisome proliferator-activated receptor.

IMPORTANT SAFETY INFORMATION

Contraindications

  • Avoid use of Orenitram in patients with severe hepatic impairment (Child Pugh Class C) due to increases in systemic exposure.

IMPORTANT SAFETY INFORMATION FOR ORENITRAM

Contraindications

  • Avoid use of Orenitram in patients with severe hepatic impairment (Child Pugh Class C) due to increases in systemic exposure.

Adverse Reactions

  • In the 12-week, placebo-controlled, monotherapy study, and an event-driven placebo-controlled, combination therapy study, adverse reactions that occurred at rates at least 5% higher on Orenitram than on placebo included headache, diarrhea, nausea, vomiting, flushing, pain in jaw, pain in extremity, hypokalemia, abdominal discomfort, and upper abdominal pain.

Warnings and Precautions

  • Abrupt discontinuation or sudden large reductions in dosage of Orenitram may result in worsening of PAH symptoms.
  • The Orenitram tablet shell does not dissolve. In patients with diverticulosis, Orenitram tablets can lodge in a diverticulum.

Drug Interactions

  • Co-administration of Orenitram and the CYP2C8 enzyme inhibitor gemfibrozil increases exposure to treprostinil; therefore, Orenitram dosage reduction may be necessary in these patients.

Specific Populations

  • Animal reproductive studies with Orenitram have shown an adverse effect on the fetus. There are no adequate and well-controlled studies with Orenitram in pregnant women.
  • It is not known whether treprostinil is excreted in human milk or if it affects the breastfed infant or milk production.
  • Safety and effectiveness of Orenitram in pediatric patients have not been established.
  • Use of Orenitram in patients aged 65 years and over demonstrated slightly higher absolute and relative adverse event rates compared to younger patients. Caution should be used when selecting a dose for geriatric patients.
  • There is a marked increase in the systemic exposure to treprostinil in hepatically impaired patients.

INDICATION

Orenitram is a prostacyclin mimetic indicated for treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to delay disease progression and to improve exercise capacity. The studies that established effectiveness included predominately patients with WHO functional class II-III symptoms and etiologies of idiopathic or heritable PAH (66%) or PAH associated with connective tissue disease (26%).

OREISIhcpOCT19

Please see Full Prescribing Information and Patient Information at www.orenitram.com or call 1-877-UNITHER (1-877-864-8437).

References: 1. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2023. 2. Del Pozo R, Hernandez Gonzalez I, Escribano-Subias P. The prostacyclin pathway in pulmonary arterial hypertension: a clinical review. Expert Rev Respir Med. 2017;11(6):491-503. 3. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004;351(14):1425-1436. 4. 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. 5. Mitchell JA, Ali F, Bailey L, et al. Role of nitric oxide and prostacyclin as vasoactive hormones released by the endothelium. Exp Physiol. 2008;93(1):141-147. 6. Humbert M, Ghofrani H-A. The molecular targets of approved treatments for pulmonary arterial hypertension. Thorax. 2016;71(1):73-83. 7. 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. 8. McLaughlin VV, Archer SL, Badesch DB, et al; ACCF/AHA. 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. Circulation. 2009;119(16):2250-2294. 9. Sitbon O, Morrell N. Pathways in pulmonary arterial hypertension: the future is here. Eur Respir Rev. 2012;21(126):321-327. 10. Guignabert C, Savale L, Boucly A, et al. Serum and Pulmonary Expression Profiles of the Activin Signaling System in Pulmonary Arterial Hypertension. Circulation. 2023;147(24):1809-1822. 11. Galiè N, Channick RN, Frantz RP, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J. 2019;53(1):1801889.