Volibris - ambrisentan

What is Volibris?

Volibris is a medicine that contains the active substance ambrisentan and is available as tablets (pale pink, square: 5 mg; dark pink, oval: 10 mg).

What is Volibris used for?

Volibris is used to treat patients with pulmonary arterial hypertension (PAH) to improve their exercise capacity (ie the possibility of exercising). PAH refers to an elevated blood pressure above the norm in the arteries of the lungs. Volibris is used in patients with PAH class II or III. The class indicates the degree of severity of the disease: "class II" means a slight limitation of physical activity while for "class III" a marked limitation of physical activity. The efficacy of Volibris has been demonstrated in cases of PAH without a recognized cause and in cases of PAH caused by diseases of the connective tissue.

Because the number of patients with PAH is low, the disease is considered "rare" and Volibris was designated an "orphan medicine" (a medicine used in rare diseases) on 11 April 2005.

The medicine can only be obtained with a prescription.

How is Volibris used?

Treatment with Volibris should be initiated by a physician experienced in the treatment of PAH.

The standard dose of Volibris is 5 mg once a day. The tablets should be swallowed whole a

full or empty stomach. A 10 mg dose may have a greater effect in patients with class III disease, however this is associated with a greater risk of fluid retention and swelling. Patients with PAH due to connective tissue disease may also need 10 mg to achieve optimal effects with Volibris. The dose should be increased only if the 5 mg dose is well tolerated.

Volibris is not recommended for use in young people under the age of 18 due to the lack of information on safety and efficacy for this group. In patients with severe kidney problems, treatment with Volibris should be initiated with caution and any dose increase should be carried out with the utmost care. Volibris should not be used in patients with severe liver problems, as the medicine has not yet been studied in this group.

How does Volibris work?

PAH is a debilitating disease that involves a severe constriction (narrowing) of the blood vessels in the lungs, resulting in an increase in blood pressure in the vessels that carry blood from the heart to the lungs. This pressure reduces the amount of oxygen that the blood can receive in the lungs, making physical activity more problematic.

The active substance in Volibris, ambrisentan, works by blocking the receptors of a hormone, endothelin, which causes the constriction of blood vessels. By blocking the effect of endothelin, Volibris allows dilation of the vessels, thus helping to lower blood pressure and improve symptoms.

What studies have been carried out on Volibris?

The effects of Volibris were first tested in experimental models before being studied in humans.

The effectiveness of Volibris has been the subject of two main studies involving a total of 394 patients with PAH, mostly class II or III (ie with slight or marked limitation of physical activity). The studies compared the various doses of Volibris (2.5, 5 and 10 mg) with a placebo (a dummy treatment).

The main measure of effectiveness was the change in the distance traveled by patients in six minutes after 12 weeks of treatment. It is a method to measure the variation in exercise capacity.

What benefit has Volibris shown during the studies?

Volibris was more effective than placebo in improving exercise capacity in patients with class II or III disease. In the two studies considered as a whole, patients treated with Volibris 5 mg once a day were able to walk, after 12 weeks of treatment, for an average of 44.6 meters more than the baseline value of about 345 meters measured at the beginning of study. In patients treated with placebo there was a reduction of 9.0 meters after 12 weeks. Patients with class III disease and patients with PAH caused by connective tissue disease achieved a greater benefit with the 10 mg dose compared to the 5 mg dose.

What is the risk associated with Volibris?

The most common side effects associated with Volibris (ie seen in more than 1 patient in 10) are headache (including sinus headache and migraine), peripheral edema (swelling, especially in the ankles and feet) and fluid retention. For the full list of all side effects reported with Volibris, see the Package Leaflet.

Volibris should not be used in patients who may be hypersensitive (allergic) to soya, ambrisentan or any of the other ingredients. Since it can cause birth defects, Volibris should not be used in pregnant women or in women who could become pregnant unless they use a reliable method of contraception. It should also not be used in breastfeeding patients, in patients with severe liver problems or with high levels of liver enzymes in the blood.

Why has Volibris been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that the benefits of Volibris outweigh the risks for the treatment of patients with PAH class II and III (according to the WHO functional classification method) to improve their exercise capacity. The committee recommended the granting of the marketing authorization for Volibris.

What measures are being taken to ensure the safe use of Volibris?

The company that makes Volibris will set up a study in the European Union (EU) on how to use the medicine once it is marketed, also agreeing with each Member State on a system to control the distribution of Volibris. The company also undertakes to prepare information packages so that healthcare professionals, patients and male partners of patients are informed about the side effects of the medicine and the need to avoid pregnancies.