Orenitram (oral treprostinil) for pulmonary arterial hypertension
Fact-checked by What is Orenitram for pulmonary arterial hypertension?
Orenitram (treprostinil) is an extended-release oral tablet formulation of treprostinil that is approved to improve exercise capacity and delay disease progression in people with pulmonary arterial hypertension (PAH).
In PAH, there is narrowing of the pulmonary arteries, which move blood from the heart to the lungs, causing pressure in those vessels to rise. Blood flow through the lungs becomes increasingly more difficult, and oxygen delivery to the body is consequently compromised.
Treprostinil, Orenitram’s active ingredient, mimics the activity of prostacyclin, a naturally occurring molecule that helps blood vessels relax and widen in a process called vasodilation. It also inhibits the activation of platelets — small cell fragments involved in blood clotting — preventing them from forming aggregates and blocking blood vessels, and prevents the growth of smooth muscle cells that can cause blood vessels to constrict. Together, these actions should help make it easier for the heart to pump blood through the lungs.
Orenitram is marketed by United Therapeutics. There are various other formulations of treprostinil that are approved in the U.S. for treating PAH, including two others from United: the infusion therapy Remodulin and Tyvaso, which is inhaled. However, Orenitram is the only one that is taken orally.
Therapy snapshot
| Brand name | Orenitram |
| Chemical name | Treprostinil |
| Usage | Used to improve exercise capacity and delay disease progression in people with PAH |
| Administration | Oral tablets |
Who can take Orenitram?
Orenitram is approved in the U.S. to delay disease progression and improve exercise capacity in people with PAH, or those belonging to Group 1 per the World Health Organization’s classification system. The clinical studies that supported its approval included predominantly patients with WHO functional class II or III symptoms, who have slight or marked limitations in performing physical activities.
Orenitram is contraindicated or not recommended for use in people with severe liver function impairments.
How is Orenitram administered?
Orenitram comes as extended-release oral tablets, which should be swallowed whole two or three times daily with food. The medication is started at a low dose and slowly increased to a maximum daily dose of 120 mg.
The dosing regimen will be adjusted for each patient by a healthcare provider based on individual needs, considering factors such as tolerability, other concomitant medications, liver health, and whether a person is transitioning from other treprostinil products. The dose should never be changed without medical supervision, as sudden changes may not be safe.
Orenitram in clinical trials
Orenitram’s safety and efficacy in PAH patients were assessed in a number of placebo-controlled Phase 3 studies.
- FREEDOM-M (NCT00325403), which showed that Orenitram led to significant improvements in exercise ability relative to a placebo among PAH patients who were not receiving any other approved treatments.
- FREEDOM-C (NCT00325442) and FREEDOM-C2 (NCT00887978), both of which showed that Orenitram failed to improve exercise abilities relative to a placebo among PAH patients who were also receiving approved PAH medications, including phosphodiesterase-5 inhibitors and/or endothelin receptor antagonists.
- FREEDOM-EV (NCT01560624), which demonstrated that Orenitram significantly delayed clinical worsening compared with a placebo when used alongside another oral background therapy.
In a long-term open-label extension study called FREEDOM-EXT (NCT01027949), which involved participants from previous Orenitram trials, the medication was associated with sustained improvements in exercise capacity.
An open-label Phase 2 trial (NCT01588405) also demonstrated that transitioning from Remodulin to Orenitram was safe and associated with clinical stability.
Orenitram side effects
The most common side effects associated with Orenitram include:
- headache
- diarrhea
- nausea
- vomiting
- jaw pain
- flushing
The outer shell of Orenitram does not dissolve and is excreted in the stool. In people with diverticulosis, an intestinal condition, the tablets may get stuck in the gastrointestinal tract.
Orenitram should never be abruptly discontinued or the dose rapidly decreased, because this can lead to a severe rebound of PAH symptoms. All dose changes should be done under the supervision of a medical professional.
Pulmonary Hypertension News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
