Last updated Feb. 3, 2023, by Lindsey Shapiro, PhD
Fact-checked by José Lopes, PhD
What is Remodulin for PH?
Remodulin (treprostinil) is an approved therapy to reduce symptoms associated with exercise in people with pulmonary arterial hypertension (PAH).
It’s also indicated to prevent clinical deterioration in patients who need to transition off of Flolan (epoprostenol).
Remodulin was developed by United Therapeutics; generic versions have also been approved.
How does Remodulin work?
In PAH, narrowing of the pulmonary arteries that carry blood to the lungs causes restricted blood flow, leading to increased blood pressure and poor oxygen transport through the body.
Treprostinil, the active ingredient in Remodulin, is a lab-made version of prostacyclin, a naturally-occurring molecule in the body that works to widen blood vessels (vasodilation).
By mimicking prostacyclin’s actions, Remodulin targets three key disease processes. First, it binds to endothelial cells on blood vessel walls and stimulates signaling pathways that drive vasodilation. It also inhibits the activation of platelets, thereby preventing them from aggregating and further blocking the arteries.
Lastly, treprostinil helps inhibit the growth of smooth muscle cells, the contraction of which works to constrict blood vessels.
Through these actions, Remodulin is designed to help blood flow through the lungs more efficiently. This should increase oxygen availability to the rest of the body, making it easier for a patient to be active.
United Therapeutics also markets two other formulations of treprostinil for PAH patients — Orenitram, an extended-release oral tablet, and Tyvaso, an inhaled version.
Who can take Remodulin?
The U.S. Food and Drug Administration (FDA) approved Remodulin in May 2002 under an accelerated approval pathway. It was indicated as an under-the-skin (subcutaneous) infusion to ease symptoms associated with exercise for PAH patients in World Health Organization (WHO) group 1.
Studies establishing its effectiveness included patients with a New York Heart Association (NYHA) functional classification II-IV or those with mild to severe limitations to physical activity.
The FDA approved Remodulin for intravenous (into-the-vein) dosing in 2004.
Remodulin is also indicated to prevent clinical worsening for PAH patients who are transitioning off Flolan.
Remodulin is similarly approved in Europe, Canada, China, Japan, and several other countries.
Who should not use Remodulin?
There are no contraindications for using Remodulin.
How is Remodulin administered?
Remodulin is supplied as a solution in vials containing 20, 50, 100, 200, or 400 mg of treprostinil.
Modes of Administration
Subcutaneous infusion is the preferred mode of administration for Remodulin and involves the continuous delivery of the therapy through a catheter inserted just under the skin. The infusion is controlled via a pump.
- The abdomen is the recommended site for the initial treatment administration.
- Patients can start subcutaneous Remodulin at home.
- Remodulin does not need to be diluted or mixed.
- Infusion pumps typically need to be refilled every two to three days.
Intravenous infusion can be used if the subcutaneous route is not well tolerated. In this case, Remodulin is delivered as a continuous intravenous infusion via a catheter inserted into a vein in the upper chest by a healthcare provider. As with the subcutaneous route, Remodulin delivery is controlled via a pump.
- Remodulin needs to be diluted for intravenous delivery with either sterile water, sodium chloride, or a high pH-glycine solution.
- In most cases, Remodulin will be initiated in the hospital, but can then be delivered at home after appropriate training on using an infusion pump approved for that purpose.
- Infusion pumps typically need to be refilled every two days.
Dosing
With either mode of administration, Remodulin is started at a dose of 1.25 nanograms per kilogram per minute (ng/kg/min) and increased weekly based on the clinical response to achieve a dose that eases symptoms and minimizes side effects. Patients with mild to moderate liver impairments should use a starting dose of 0.625 ng/kg/min.
Over the first four weeks, the weekly increase should be by 1.25 ng/kg/min, followed by 2.5 ng/kg/min thereafter as needed. Abrupt treatment cessation should be avoided.
For patients transitioning from Flolan, the Remodulin dose is gradually increased, starting at a recommended dose of 10% of the current Flolan dose, while Flolan is gradually decreased. This transition should be performed in the hospital with constant monitoring.
Remodulin in clinical trials
PAH patients in NYHA class II-IV
The FDA based its initial approval of Remodulin on results from two 12-week, multicenter clinical trials involving 470 PAH patients who were randomized to receive either subcutaneous Remodulin or a placebo.
The primary goal of these trials was to assess Remodulin’s effects on exercise capacity, as assessed by the six-minute walking distance (6MWD) test, which evaluates how far a person can walk in six minutes.
While those in the Remodulin group improved their 6MWD by a median of about 10 meters, compared with no improvement in the placebo group, the difference in improvement was not statistically significant after 12 weeks of treatment.
Borg dyspnea scores, a measure of breathlessness during exercise, were significantly reduced after 12 weeks of Remodulin compared with a placebo, reflecting a reduction in breathlessness. A combined measure of Borg dyspnea scores and 6MWD performance also significantly favored Remodulin over a placebo.
Other indices of breathlessness, fatigue, and pulmonary hypertension symptoms were similarly improved with Remodulin treatment.
Long-term safety and effectiveness
A long-term open-label study evaluated subcutaneous Remodulin’s safety and effectiveness in 860 patients who were followed for up to four years.
Overall survival was 87% after one year and 68% after four years. Of the 860 patients, 199 discontinued treatment due to side effects. Moreover, 97 people stopped using the treatment to switch to a different prostacyclin analogue.
The treatment’s safety profile was consistent with previous short-term studies.
Flolan-to-Remodulin Transition Study
An eight-week clinical trial (NCT00058929) tested whether switching from Flolan to Remodulin was safe and effective. A total of 22 patients completed the study.
Results showed Remodulin prevented clinical deterioration in patients transitioning from Flolan compared with a placebo. Particularly, 13 of 14 patients given Remodulin were able to transition successfully, compared with one of eight people in the placebo group.
Other trials
A Phase 2 clinical trial (NCT02261883) evaluated the effectiveness of Remodulin as an add-on treatment to standard therapies for babies with persistent pulmonary hypertension of the newborn. The study was expected to finish in December 2022.
Common side effects of Remodulin
The most common side effects associated with Remodulin include:
- subcutaneous infusion site pain and reaction
- headache
- diarrhea
- nausea
- jaw pain
- blood vessel widening (vasodilation)
- swelling (edema)
- low blood pressure (hypotension)
Infusion-related reactions
Infusion site pain and reactions, including redness, swelling and rash, are common side effects associated with subcutaneous Remodulin. These side effects have been reported as severe for some patients, requiring treatment with narcotics or discontinuation of Remodulin in some cases.
Infusion site pain is not typically observed with intravenous administration.
Catheter-related bloodstream infections
Intravenous Remodulin is associated with a risk of bloodstream infections and sepsis, a type of life-threatening response to infection. For this reason, subcutaneous Remodulin is the preferred route of administration, when possible.
When intravenous use is needed, diluting Remodulin in a glycine solution with a high pH has been associated with a reduced risk of infection.
Worsening PAH when stopping treatment
PAH symptoms may significantly worsen if Remodulin is abruptly stopped or if the dose is quickly decreased. Treatment should not be stopped abruptly, but should be tapered off at the discretion of a healthcare provider.
Liver problems
Patients with liver problems may be exposed to higher concentrations of Remodulin. Such patients should titrate up the dose of Remodulin more slowly.
Hypotension
Because Remodulin works as a vasodilator, patients with low systemic blood pressure may experience symptoms of hypotension. Such symptoms may include lightheadedness, blurred vision, weakness, confusion or fainting.
Bleeding
Remodulin inhibits the aggregation of platelets, which are involved in blood clotting and therefore may increase the risk of bleeding.
Pregnancy and breastfeeding
Few studies have evaluated Remodulin’s use by pregnant or breastfeeding women. Preclinical studies have not demonstrated a risk of fetal toxicity at clinically relevant doses. Patients who are pregnant or wish to become pregnant while using Remodulin should talk with their healthcare team.
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.
