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Dosing & Titration

Dosing to Meet Individualized Needs

Dosing With Orenitram

Assess RISK.

Consider TIME.

Leverage ORENITRAM.

Reaching an initial target TDD of ≥9 mg is important to achieving clinical improvement, but individual patient needs may vary.1,2 Selecting the appropriate dosing approach may help you and your patients reach this goal.

Dosing with Orenitram

5 Tablet Strengths for Flexible Dosing

Multiple tablet strengths provide dosing flexibility to meet your patient’s unique clinical needs, and allows them to continue to titrate to reach maximum clinical benefit.1*

Orenitram 0.125 mg tablet
Orenitram 0.25 mg tablet
Orenitram 1 mg tablet
Orenitram 2.5 mg tablet
Orenitram 5 mg tablet

Tablets are not shown to actual size.

*Maximum labeled dose for Orenitram is 120 mg TDD.1

View Transcript

Optimizing Treatment Through Flexible Dosing with Orenitram

Discover how flexible dosing with Orenitram can help address the evolving needs of intermediate risk PAH patients. This video highlights the importance of dose-response in optimizing risk parameters before patients progress further.2

Support a TID dosing schedule

Orenitram is best tolerated TID every 8 hours with food, as this may help to reduce peak-to-trough fluctuations.1

Breakfast (6A-8A)

8 HOURS

Afternoon Snack (2P-4P)

8 HOURS

Bedtime Snack (10P-12A)

Choose the Appropriate Dosing Approach for Your Patients’ Clinical Needs

Reaching a therapeutic dose is important to achieving clinical improvement, but individual patient needs may vary based on1 :

Clipboard icon

RISK

assessment

Clock icon

TIME needed to reach necessary exposure

Up and down arrows with blue-purple gradient

DOSING PREFERENCE to achieve goals

Select a Dosing Approach for Prostacyclin-Naïve Patients2:

  • For lower risk patients with less severe disease, initiate Orenitram at a low dose with slow up-titration to manage side effects
Orenitram Titration Kit weekly boxes

The Orenitram Titration Kit

An all-in-one kit helps simplify titration and build confidence as patients reach necessary exposure1

See How It Works
  • For higher risk patients, consider parenteral therapy. If and when appropriate, transition to a comparable dose of Orenitram†

†Transition may be appropriate for hemodynamically stable patients.

Transitioning Appropriate Prostacyclin-Experienced Patients2:

Red and violet triangles pointing at each other and forming a rectangle

Transitioning From Remodulin to Orenitram

For hemodynamically stable patients, an established plan to transition from Remodulin® (treprostinil) Injection to Orenitram

See the Study
Up and down arrows with blue-purple gradient

For patients on current therapy, evidence from a peer-reviewed article supports that patients who have reached dose limits or are at risk for discontinuation due to tolerability might be candidates for Orenitram2

Orenitram 90 Day Trial Program logo

Did you know that eligible patients may start treatment on the Orenitram Titration Kit at no cost for up to 90 days?

Learn More

Evolution of Orenitram: Dosing and Patient Management6-13

 

2012 - 2013

STUDIES & PUBLICATIONS

FREEDOM-C† (N=350) 16-week

  • Initiated at 0.5 mg BID, increased by 0.5 mg BID every 3 days

FREEDOM-M (N=349) 12-week

  • Initiated at 0.25 mg BID, increased by 0.25 or 0.5 mg BID every 3 days

FREEDOM-C2† (N=310) 16-week

  • Initiated at 0.25 mg BID, increased by 0.25 mg BID every 3 days

DOSING (MG TDD)‡

6-6.8

LEARNINGS

BID Dosing May Be Challenging in Some Patients

2014

STUDIES & PUBLICATIONS

REAL-WORLD CLINICAL SETTING (N=1200) 78-week

DOSING (MG TDD)‡

10.8

LEARNINGS

Meal-Enhanced Absorption14

2017

STUDIES & PUBLICATIONS

TRANSITION STUDY (N=33) 24-week

DOSING (MG TDD)‡

39.5

LEARNINGS

Stable Transition from Remodulin, Expert AE Management Consensus

2019

STUDIES & PUBLICATIONS

FREEDOM-EV† (N=690) 48-week

  • Initiated at 0.125 mg TID, increased by 0.125 mg every day for 4 weeks and 0.25 mg thereafter, to a maximum dose of 12 mg

DOSING (MG TDD)‡

10.7

LEARNINGS

TID Preferred

2022

STUDIES & PUBLICATIONS

FREEDOM-EV HEMODYNAMIC SUBSTUDY (N=61) 24-week

DOSING (MG TDD)‡

16.5

LEARNINGS

Hemodynamic effects of Orenitram

2024

STUDIES & PUBLICATIONS

FREEDOM-EV OLE (N=470) 48-week||

DOSING (MG TDD)‡

18.3

LEARNINGS

9 mg Initial Target TDD;2
1st, 2nd-line, Refractory AE Management Published;2

Every patient is different.

11.5 mg

Real World average TDD of Orenitram at 3 months

Based on Specialty Pharmacy shipment data through May 2025 inclusive of de novo and transition patients.4

"There’s been a learning curve [with Orenitram] and the more recent studies have shown that we’re learning how to use it better"

— PAH expert

‡In FREEDOM-C, median dose of 3 mg BID is from week 16.8 In FREEDOM-M, Orenitram was first initiated at 1 mg. After study protocol revisions, the starting dosage was changed to 0.5 mg, then, 0.25 mg. Mean dose of 3.4 mg BID is from week 12.9 In FREEDOM-C2, mean dose of 3.1 mg BID is from week 16.10 In Real-World Clinical Setting, median dose of 10.8 mg TDD at month 18 is from medication shipment records of a representative sample of patients taking Orenitram TID.11 In the Transition Study, subjects were administered Orenitram TID while simultaneously decreasing the Remodulin dose (from a baseline Remodulin dose of 57 ng/kg/min). Mean dose of 39.5 mg TDD is from week 24.7 In FREEDOM-EV, median dose of 3.56 mg TID is from week 24.6 In the FREEDOM-EV hemodynamic substudy, median dose of 5.5 mg TID is from week 24.12 In FREEDOM-EV OLE, patients initially randomized to Orenitram continued at their previous dose and were able to titrate further without limitation. These patients reached a mean dose of 6.1 mg TID 48 weeks after enrollment in the OLE.13

§These trials did not achieve significance for their respective primary endpoints.8,10

||Indicated time points show when mean/median doses were measured. Event-driven study duration was not predefined.

Dosing and AE Management as a Team

Franck Rahaghi, MD, and Starlet Harrimon, RN, discuss how they work with patients to plan for expected adverse effects with Orenitram.

United Therapeutics does not provide medical advice. Adverse effect management strategies should be addressed in accordance with the Orenitram Full Prescribing Information and your clinical judgment.

Frequently Asked Questions

United Therapeutics does not provide medical advice. Adverse event management or dosing strategies should be dealt with in accordance with the Orenitram Full Prescribing Information and your clinical judgment.

Orenitram Titration Kit

Discover how the Titration Kit may help your patient start Orenitram with confidence.

Transitioning to Orenitram

See why stable patients on parenteral prostacyclin who switch to Orenitram may transition successfully.

A Confident Start

Read about the steps you and your patient may take to help them feel confident as they begin taking Orenitram.

AE=adverse effect; BID=2 times daily; PAH=pulmonary arterial hypertension; TDD=total daily dose; TID=3 times daily.

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. Brewer J, Wilson M, Coons JC, et al. Practical management of oral treprostinil in patients with pulmonary arterial hypertension: Lessons from ADAPT, EXPEDITE, and expert consensus. Respir Med. 2024;231:107734. 3. Rahaghi FF, Feldman JP, Allen RP, et al. Recommendations for the use of oral treprostinil in clinical practice: a Delphi consensus project pulmonary circulation. Pulm Circ. 2017;7(1):167-174. 4. Data on file. United Therapeutics Corporation. Research Triangle Park, NC. 5. White RJ, Grunig 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 Conference; September 27 to October 2 2019; Madrid, Spain. 6. White RJ, Jerjes-Sanchez C, Bohns Meyer GM, et al; FREEDOM-EV Investigators. Combination therapy with oral treprostinil for pulmonary arterial hypertension. A double-blind placebo controlled clinical trial. Am J Respir Crit Care Med. 2020;201(6):707-717. 7. Chakinala MM, Feldman JP, Rischard F, et al. Transition from parenteral to oral treprostinil in pulmonary arterial hypertension. J Heart Lung Transplant. 2017;36(2):193-201. 8. 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. 9. 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. 10. 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. 11. Balasubramanian VP, Messick CR, Broderick M, Nelsen AC. Dosing characteristics of oral treprostinil in real-world clinical practice. Pulm Circ. 2018;8(2):2045894018770654. 12. Khan A, White RJ, Meyer G, et al. Oral treprostinil improves pulmonary vascular compliance in pulmonary arterial hypertension. Respir Med. 2022;193:106744. 13. Grünig E, Rahaghi F, Elwing J, et al. Oral Treprostinil is Associated with Improved Survival in FREEDOM-EV and its Open-Label Extension. Adv Ther. 2024;41(2):618-637. 14. Lim A, Wang-Smith L, Kates J, Laurent A, Kumar P, Laliberte K. The effect of different meal compositions on the oral bioavailability of treprostinil diolamine in healthy volunteers. J Clin Pharm Ther. 2013;38(6):450-455.