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Expected Adverse Events With Orenitram

Adverse Events in FREEDOM-EV

The safety profile in FREEDOM-EV was consistent with previous studies of Orenitram and known prostacyclin-related adverse events.1-5*

*Previous studies included FREEDOM-M, FREEDOM-C, FREEDOM-C2, and FREEDOM-EXT.1-5

Adverse Events With Rates at Least 5% Higher on Orenitram Than on Placebo in FREEDOM-EV (N=690)1
ReactionOrenitram
n=346		Placebo
n=344
Headache75%35%
Diarrhea69%29%
Flushing45%8%
Nausea40%23%
Vomiting36%10%
Pain in jaw18%3%
Pain in extremity18%9%
Upper abdominal pain12%5%

19% of patients on Orenitram and 4% of those receiving placebo discontinued treatment due to adverse events.1

Managing Adverse Effects

See how to work proactively with patients to help prepare them for the challenges of expected adverse effects.

Getting Patients Started

Find out how you may set your patient up for a successful start on Orenitram.

Video and Resource Library

To access helpful videos, downloadable resources for patients, and recent publications, visit Video and Resource Library.

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. White RJ, Parikh K, Allen R, et al. Long-term study of oral treprostinil to treat pulmonary arterial hypertension: dosing, tolerability, and pharmacokinetics. Pulm Circ. 2020;10(4):1-9. 3. Jing ZC, 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. 4. Tapson VF, Torres F, Kermeen F, et al. Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial. Chest. 2012;142(6):1383-1390. 5. Tapson VF, Jing ZC, Xu KF, et al; FREEDOM-C2 Study Team. Oral treprostinil for the treatment of pulmonary arterial hypertension in patients receiving background endothelin receptor antagonist and phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C2 study): a randomized controlled trial. Chest. 2013;144(3):952-958.