Flolan (epoprostenol sodium) for pulmonary arterial hypertension

What is Flolan for pulmonary arterial hypertension?

Flolan (epoprostenol sodium) is an approved intravenous infusion therapy used to improve exercise capacity in people with pulmonary arterial hypertension (PAH). In 1995, it became the first treatment approved for PAH in the U.S.

In PAH, the pulmonary arteries, the vessels that carry blood from the heart to the lungs, become narrowed. Increased pressure in those arteries then makes it harder for the heart to pump blood, limiting oxygen transport through the body, and making exercise more difficult.

Flolan’s active ingredient, epoprostenol, is a lab-made version of prostacyclin, a naturally occurring molecule that helps blood vessels relax and widen, a process known as vasodilation. It also prevents platelets, the cell fragments involved in blood clotting, from forming aggregates and blocking blood vessels. By mimicking these effects of prostacyclin, Flolan makes it easier for the heart to pump blood through the lungs, giving PAH patients a greater ability to be active.

Flolan is marketed by GlaxoSmithKline, with generic versions also available in the U.S. Actelion Pharmaceuticals, now part of Johnson & Johnson, developed another formulation of epoprostenol called Veletri (epoprostenol AS), which works similarly but is designed to be more stable at room temperature.

Therapy snapshot

Who can take Flolan?

Flolan is approved in the U.S. to improve exercise capacity in PAH patients, or those belonging to Group 1 of the World Health Organization’s classification system. Flolan is also widely approved for PAH in other countries worldwide.

Studies establishing its effectiveness nearly exclusively included people with a New York Heart Association functional classification III-IV, or those with marked to severe symptoms during physical activity.

According to the U.S. prescribing label, Flolan is contraindicated, or should not be used by:

• people with heart failure with reduced ejection fraction, where the heart is not able to pump out enough blood to the rest of the body during a heartbeat
• people with a history of serious immune responses, or hypersensitivity, to Flolan or any of its ingredients

How is Flolan administered?

Flolan is administered as a continuous intravenous, or into-the-vein, infusion. A doctor will insert a tiny tube called a catheter into a vein, through which the medication is delivered directly into the bloodstream. The infusion is controlled by an external, battery-operated pump.

The medication comes as a powder that is dissolved in a liquid before administration. Treatment is initiated under close medical supervision, with the dose and infusion rate adjusted based on a person’s clinical response and side effects.

Thereafter, if deemed safe by a physician, patients or caregivers may be able to give Flolan infusions at home. In this case, they will be educated on medication preparation and administration, catheter care, and the use of the infusion pump. However, patients should never change the dose or stop treatment without consulting their healthcare provider.

Flolan in clinical trials

A number of randomized clinical trials, observational studies, and registries have evaluated Flolan’s safety and efficacy in people with PAH over the last few decades:

• The effects of Flolan in people with idiopathic or heritable PAH were studied in two open-label trials. The data showed that when used in conjunction with standard PAH therapies, Flolan led to improvements in blood flow and exercise capacity relative to standard treatment alone, as well as reductions in fatigue, breathlessness, and mortality rates.
• Another clinical trial evaluated the effects of Flolan in people with PAH associated with the connective tissue disease systemic sclerosis. Similar to earlier studies, Flolan, when combined with standard care, led to significant improvements in exercise capacity and blood flow relative to standard care alone.

Flolan became contraindicated for people with heart failure with reduced ejection fraction based on results from the Flolan International Randomized Survival Trial. Interim trial results showed that Flolan was associated with an increased mortality rate in these patients.

Flolan side effects

The most common side effects associated with Flolan are usually related to vasodilation and include:

• dizziness
• jaw pain
• headache
• musculoskeletal pain
• nausea or vomiting

Other, less common, but potentially serious side effects of Flolan include:

• fluid buildup in the lungs, called pulmonary edema
• vasodilation reactions, including blood pressure drops and symptoms such as nausea, vomiting, dizziness, and headache
• bleeding events, especially if other risk factors are present, due to Flolan’s effects on platelets

Patients will be closely monitored for these side effects, particularly when starting treatment and with dose adjustments. In some cases, treatment may need to be stopped.

Any changes to Flolan administration should always be done under medical supervision. PAH symptoms may get worse and be potentially life-threatening if treatment is abruptly discontinued or the dose is suddenly lowered.