Skip to content

Orenitram Is the Only Oral Prostacyclin Mimetic for PAH1

Prostacyclin Is Important for Normal Lung Function2

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.2,4

Prostacyclin Synthase Expression in Pulmonary Arteries2*
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).2

As a Prostacyclin Mimetic, Treprostinil Acts on Multiple Receptors3,5,6

Prostacyclin mimetics are synthetic drugs designed to supplement the endogenous prostacyclin that patients with PAH may be lacking.2,7

TREPROSTINIL3,5,6

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)

The Mechanism of Action of Orenitram Targets 3 of the Major Pathologic Changes That Occur in PAH1,8

Vessel Affected by PAH

Orenitram oral prostacyclin mechanism of action

  1. Vasoconstriction

    Orenitram directly dilates pulmonary and systemic arterial vascular beds

  2. Platelet aggregation

    Orenitram inhibits platelet aggregation

  3. Smooth muscle proliferation

    Orenitram inhibits smooth muscle cell proliferation

Prostacyclin Is One of the 3 Established Pathways in PAH3,8,9

Targeting multiple pathogenic pathways is now standard of care.10

  • Prostacyclin
    pathway3

  • Endothelin
    pathway3

  • Nitric oxide
    pathway3

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.

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.

IMPORTANT SAFETY INFORMATION

Contraindications

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

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.

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.

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 for Orenitram.

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

References: 1. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2023. 2. 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. 3. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004;351(14):1425-1436. 4. 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. 5. 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. 6. 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. 7. Humbert M, Ghofrani H-A. The molecular targets of approved treatments for pulmonary arterial hypertension. Thorax. 2016;71(1):73-83. 8. 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. 9. Sitbon O, Morrell N. Pathways in pulmonary arterial hypertension: the future is here. Eur Respir Rev. 2012;21(126):321-327. 10. Galiè N, Channick RN, Frantz RP, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J. 2019;53(1):1801889.