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Start with Orenitram, oral treprostinil—titrate to achieve the appropriate dose for each patient1

5 tablet strengths offer flexibility to titrate to clinical response and tolerability, with no labeled maximum dose1

Orenitram dosing options

How to dose Orenitram1



at the starting dose of 0.125 mg TID



gradually with ~weekly increases of 0.125 mg TID, or as tolerated*



dose to achieve appropriate therapeutic benefits

Monitor for continued clinical response and tolerability. Titrate down or at a slower rate, if needed
  • You can also choose a BID (~12 hours apart) dosing schedule, starting at 0.25 mg BID and titrating in 0.25 mg BID increments as tolerated1
  • Titrate no more frequently than every 3 to 4 days.1
Proactively Manage Side Effects

Titrating at 0.125 mg TID ~weekly will allow patients to reach a target dose of 3 mg TID by 6 months1

Example Monthly Titration Schedule1
Orenitram titration schedule example

In FREEDOM-EV, achieving doses of ≥3 mg TID was associated with greater improvements in 6MWD2

  • Change in 6MWD was not statistically significant at week 24 for the ITT population3

Additional dosing considerations1

  • Each dose should be taken with food
  • Orenitram tablets should be swallowed whole; advise patients not to crush, split, or chew

Managing missed doses1

  • 1 missed dose: instruct your patient to take the missed dose as soon as possible with food
  • 2 or more missed doses: restart treatment at a lower dose and retitrate

Dose interruption or discontinuation1

Situations may arise where you need to temporarily interrupt oral therapy and use parenteral therapy. Follow these guidelines to help maintain consistent therapy:

  • Abrupt discontinuation or sudden large reductions in dosage of Orenitram may result in worsening of PAH symptoms
  • For planned short-term interruption: consider a temporary infusion of subcutaneous or intravenous Remodulin (treprostinil) Injection
  • For planned discontinuation: reduce the dose in steps of 0.5 to 1 mg per day
  • If dose increments are not tolerated, try slowing or temporarily stopping titration. You can also down-titrate if needed. Avoid abrupt discontinuation

Dose adjustment in patients with hepatic impairment or use with CYP2C8 inhibitors1

  • In patients with mild hepatic impairment (Child Pugh Class A), start at 0.125 mg BID with 0.125 mg BID dose increments not more frequently than every 3 to 4 days
  • Avoid use of Orenitram in patients with moderate hepatic impairment (Child Pugh Class B)
  • Orenitram is contraindicated in patients with severe hepatic impairment (Child Pugh Class C) due to increases in systemic exposure
  • When co-administered with strong CYP2C8 inhibitors (eg, gemfibrozil), the initial dose is 0.125 mg BID with 0.125 mg BID dose increments not more frequently than every 3 to 4 days
Proactively Manage Side Effects

Important Safety Information


  • 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.


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%).


Please see Full Prescribing Information and Patient Information for Orenitram.

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

6MWD=6-minute walk distance; BID=2 times daily; ITT=intent-to-treat; PAH=pulmonary arterial hypertension; TDD=total daily dose; TID=3 times daily.

References: 1. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2019. 2. White RJ, Grünig E, Jerjes-Sanchez C, et al. Dose-response relationship of oral treprostinil for secondary endpoints in the FREEDOM-EV study. Poster presented at: European Respiratory Society International Congress; September 28-October 2, 2019; Madrid, Spain. 3. Data on file. United Therapeutics Corporation. Research Triangle Park, NC.