Volibris

ambrisentan

This is a summary of the European public assessment report (EPAR) for Volibris. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Volibris.

What is Volibris?

Volibris is a medicine that contains the active substance ambrisentan. It is available as tablets (5 and 10 mg).

What is Volibris used for?

Volibris is used to treat adults with pulmonary arterial hypertension (PAH) to improve exercise capacity (the ability to carry out physical activity). PAH is abnormally high blood pressure in the arteries of the lungs. Volibris is used in patients with class-II or -III disease. The ‘class’ reflects the seriousness of the disease: ‘class II’ involves slight limitation of physical activity and ‘class III’ involves marked limitation of physical activity. Volibris has been shown to be effective in PAH with no identified cause and in PAH caused by connective tissue disease.

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 must be started by a doctor who has experience in the treatment of PAH.

The standard dose of Volibris is 5 mg once a day. The tablets should be swallowed whole. A 10-mg dose may have a greater effect in patients with class-III disease but this is associated with an increased risk of fluid retention and swelling. Patients with PAH caused by connective-tissue disease may also need to take 10 mg to get the best benefit from Volibris. The dose should only be increased if the 5-mg dose is well tolerated. Patients also taking ciclosporin (a medicine that reduces the activity of the immune system) should not take more than 5 mg Volibris a day and should be closely monitored by their doctor.

How does Volibris work?

PAH is a debilitating disease where there is severe constriction (narrowing) of the blood vessels of the lungs. It causes high blood pressure in the vessels taking blood from the heart to the lungs. This pressure reduces the amount of oxygen that can get into the blood in the lungs, making physical activity more difficult. The active substance in Volibris, ambrisentan, blocks the receptors for a hormone called endothelin, which causes blood vessels to constrict. By blocking the effect of endothelin, Volibris allows the vessels to dilate (expand), helping to lower the blood pressure and improving symptoms.

How has Volibris been studied?

Various doses of Volibris (2.5, 5 and 10 mg) have been compared with placebo (a dummy treatment) in two main studies involving a total of 394 patients with PAH, most of whom had class-II or -III disease that was of unknown cause or caused by connective-tissue disease. The main measure of effectiveness was the change in the distance the patients could walk in six minutes after 12 weeks of treatment. This is a way of measuring the change in exercise capacity.

What benefit has Volibris shown during the studies?

Volibris was more effective than placebo at improving exercise capacity in patients with class-II or -III disease. Overall, in the two studies taken together, the patients could walk an average of around 345 metres in six minutes at the start of the study. The patients taking 5 mg Volibris once a day could walk an average of 36 metres more after 12 weeks of treatment, while the patients taking placebo could walk 9 metres less. Patients with class-III disease and those with PAH caused by connective tissue disease gained a greater benefit from the 10-mg dose than from the 5-mg dose.

What is the risk associated with Volibris?

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

Volibris must not be used in people who are hypersensitive (allergic) to soya, ambrisentan or any of the other ingredients. Because it might be able to cause birth defects, Volibris must not be used in pregnant women or in women who could become pregnant unless they are using reliable contraception. It must not be used in patients who are breast-feeding, who have severe liver problems or who have high levels of liver enzymes in the blood. It must not be used in patients with idiopathic pulmonary fibrosis (long-term disease in which hard fibrous tissue continuously forms in the lungs), with or without secondary pulmonary hypertension (high blood pressure in the lungs).

Why has Volibris been approved?

The CHMP decided that Volibris’s benefits are greater than its risks and recommended that it be given marketing authorisation.

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

The company that makes Volibris has agreed with EU Member States on systems to control the distribution of Volibris. The company also distributes information packs to provide healthcare workers, patients, and the male partners of female patients with information on the medicine’s side effects and the need to avoid pregnancy.

Other information about Volibris

The European Commission granted a marketing authorisation valid throughout the EU for Volibris on 21 April 2008.

For more information about treatment with Volibris, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This EPAR was last updated on 06/06/2013 .

More detail is available in the summary of product characteristics

Product details

Publication details

Product information

18/04/2013  Volibris -EMEA/H/C/000839 -IG/0279

Contents

• Annex I - Summary of product characteristics
• Annex IIA - Manufacturing-authorisation holder responsible for batch release
• Annex IIB - Conditions of the marketing authorisation
• Annex IIIA - Labelling
• Annex IIIB - Package leaflet

Please note that the size of the above document can exceed 50 pages.

You are therefore advised to be selective about which sections or pages you wish to print.

Pharmacotherapeutic group

Antihypertensives

Therapeutic indication

Volibris is indicated for the treatment of patients with pulmonary arterial hypertension (PAH) classified as World Health Organization functional class II and III, to improve exercise capacity. Efficacy has been shown in idiopathic PAH (IPAH) and in PAH associated with connective-tissue disease.

Changes since initial authorisation of medicine

Initial marketing-authorisation documents