Stayveer

bosentan monohydrate

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This is a summary of the European public assessment report (EPAR) for Stayveer. It explains how the Agency assessed the medicine to recommend its authorisation in the European Union (EU) and its conditions of use. It is not intended to provide practical advice on how to use Stayveer.

For practical information about using Stayveer, patients should read the package leaflet or contact their doctor or pharmacist.

What is Stayveer and what is it used for?

Stayveer is a medicine that contains the active substance bosentan. It is used to treat patients with class-III pulmonary arterial hypertension (PAH) to improve exercise capacity (the ability to carry out physical activity) and symptoms. PAH is abnormally high blood pressure in the arteries of the lungs. The ‘class’ reflects the seriousness of the disease: ‘class III’ involves marked limitation of physical activity. The PAH can be:

  • primary (with no identified cause or inherited);
  • caused by scleroderma (also called systemic sclerosis, a disease where there is abnormal growth of the connective tissue that supports the skin and other organs);
  • caused by congenital (inborn) heart defects with shunts (abnormal passageways) causing abnormal flow of blood through the heart and lungs.

Some improvements have also been shown in patients with class-II PAH. ‘Class II’ involves slight limitation of physical activity.

Stayveer can also be used in adults with systemic sclerosis in whom poor blood circulation caused by the disease has led to the development of ‘digital ulcers’ (sores on the fingers and toes). Stayveer is intended to reduce the number of new digital ulcers that are formed.

This medicine is the same as Tracleer, which is already authorised in the European Union (EU). The company that makes Tracleer has agreed that its scientific data can be used for Stayveer (‘informed consent’).

How is Stayveer used?

Stayveer can only be obtained with a prescription and treatment should only be started and monitored by a doctor who has experience in the treatment of PAH or systemic sclerosis.

Stayveer is available as tablets (62.5 mg and 125 mg), which are swallowed with water. It is taken morning and evening. In adults, the starting dose is 62.5 mg twice a day for four weeks, which is increased to the usual dose of 125 mg twice a day. In children with PAH, the dose to use is calculated based on body weight, and usually starts at 2 mg per kilogram body weight twice a day. See the package leaflet for full details.

The doctor should assess the patient’s response to Stayveer and review the need for further treatment after eight weeks in patients with PAH who have not improved, and on a regular basis in patients with systemic sclerosis and ongoing digital ulcer disease. If the doctor decides to stop Stayveer, the dose should be gradually reduced.

Patients who take Stayveer must be given the special reminder card that summarises the safety information about the medicine.

How does Stayveer work?

The active substance in Stayveer, bosentan, blocks a naturally occurring hormone called endothelin-1 (ET-1), which causes blood vessels to narrow. Stayveer therefore causes blood vessels to expand.

PAH is a debilitating disease where there is severe narrowing of the blood vessels of the lungs. It causes high blood pressure in the vessels taking blood from the right side of 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. By expanding these blood vessels, the blood pressure is reduced and symptoms are improved.

In patients with systemic sclerosis and ongoing digital ulcer disease, bosentan improves blood circulation in the fingers and toes, preventing the development of new digital ulcers.

What benefits of Stayveer have been shown in studies?

In PAH, Stayveer has been studied in four main studies: two in a total of 245 adults with class-III or -IV disease that was either primary or caused by scleroderma, one in 54 adults with class-III PAH that was associated with congenital heart defects, and one in 185 patients with class-II disease. The studies compared Stayveer with placebo (a dummy treatment), when they were added to standard treatment. The main measure of effectiveness was how far the patients could walk in six minutes (a way of measuring exercise capacity), but the study in class-II disease also looked at the change in the resistance to blood flow in the lungs’ blood vessels (a marker of how narrow the blood vessels are).

In class-III or -IV PAH that was either primary or caused by scleroderma, the two studies showed that patients treated with Stayveer were able to walk further than patients treated with placebo after 16 weeks (44 metres further in the larger study), but there were too few patients with class-IV disease to support the use of the medicine in this group. Similar results were seen in the patients with congenital heart defects. In patients with class-II disease, Stayveer caused the resistance of the blood vessels to decrease by 23% compared with placebo after six months of treatment, but the distance the patients could walk over six minutes was similar in the two groups. A study was also carried out in 19 children aged between three and 15 years, where some improvements were seen in measurements relating to the heart and arteries.

In systemic sclerosis with digital ulcers, two studies have compared Stayveer with placebo in a total of 312 adults. The main measure of effectiveness was based on the number of new digital ulcers developing during the studies. One of the studies also looked at the effect of Stayveer on healing in 190 patients, by measuring the time taken for one selected digital ulcer in each patient to heal completely. Stayveer was more effective at reducing the development of new digital ulcers than placebo. In the first study, patients taking Stayveer had an average of 1.4 new digital ulcers after 16 weeks, compared with 2.7 in the patients taking placebo. Similar results were seen in the second study after 24 weeks, but Stayveer did not have any effect on digital-ulcer healing.

What are the risks associated with Stayveer?

In PAH, the most common side effects with Stayveer (which may affect more than 1 patient in 10) are headache and abnormal results of tests carried out to check the liver. In patients with digital ulcers, the most common side effects (which may affect more than 1 patient in 10) are abnormal liver tests, oedema (swelling) and fluid retention. Because of the risk of liver problems, the doctor will measure the levels of liver enzymes before treatment, and every month during treatment with Stayveer. For the full list of all side effects reported with Stayveer, see the package leaflet.

Stayveer must not be used in patients who have certain liver problems, who are pregnant or could become pregnant because they are not using reliable contraceptive methods or who are taking ciclosporin A (a medicine that acts on the immune system). For the full list of restrictions, see the package leaflet.

Why is Stayveer approved?

The Agency’s Committee for Medicinal Products for Human Use (CHMP) decided that Stayveer’s benefits are greater than its risks and recommended that it be approved for use in the EU.

What measures are being taken to ensure the safe and effective use of Stayveer?

A risk-management plan has been developed to ensure that Stayveer is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Stayveer, including the appropriate precautions to be followed by healthcare professionals and patients.

In addition, the company that makes Stayveer will provide an educational kit for prescribers and an information booklet for patients in each Member State, explaining the safety of Stayveer (especially its effects on the liver and in pregnancy) and its interactions. The company will also carefully control the distribution of the medicine in each Member State, and collect information on its use in patients with systemic sclerosis and ongoing digital ulcers.

Other information about Stayveer

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

Name Language First published Last updated
Stayveer : EPAR - Summary for the public BG = bălgarski 2013-07-02  
Stayveer : EPAR - Summary for the public ES = español 2013-07-02  
Stayveer : EPAR - Summary for the public CS = čeština 2013-07-02  
Stayveer : EPAR - Summary for the public DA = dansk 2013-07-02  
Stayveer : EPAR - Summary for the public DE = Deutsch 2013-07-02  
Stayveer : EPAR - Summary for the public ET = eesti keel 2013-07-02  
Stayveer : EPAR - Summary for the public EL = elliniká 2013-07-02  
Stayveer : EPAR - Summary for the public EN = English 2013-07-02  
Stayveer : EPAR - Summary for the public FR = français 2013-07-02  
Stayveer : EPAR - Summary for the public IT = italiano 2013-07-02  
Stayveer : EPAR - Summary for the public LV = latviešu valoda 2013-07-02  
Stayveer : EPAR - Summary for the public LT = lietuvių kalba 2013-07-02  
Stayveer : EPAR - Summary for the public HU = magyar 2013-07-02  
Stayveer : EPAR - Summary for the public MT = Malti 2013-07-02  
Stayveer : EPAR - Summary for the public NL = Nederlands 2013-07-02  
Stayveer : EPAR - Summary for the public PL = polski 2013-07-02  
Stayveer : EPAR - Summary for the public PT = português 2013-07-02  
Stayveer : EPAR - Summary for the public RO = română 2013-07-02  
Stayveer : EPAR - Summary for the public SK = slovenčina 2013-07-02  
Stayveer : EPAR - Summary for the public SL = slovenščina 2013-07-02  
Stayveer : EPAR - Summary for the public FI = suomi 2013-07-02  
Stayveer : EPAR - Summary for the public SV = svenska 2013-07-02  

This EPAR was last updated on 12/10/2016 .

Authorisation details

Product details

Product details for Stayveer
NameStayveer
Agency product numberEMEA/H/C/002644
Active substance

bosentan monohydrate

International non-proprietary name (INN) or common name

bosentan monohydrate

Therapeutic area Hypertension, PulmonaryScleroderma, Systemic
Anatomical therapeutic chemical (ATC) code C02KX01

Publication details

Publication details for Stayveer
Marketing-authorisation holder

Marklas Nederlands BV   

Revision4
Date of issue of marketing authorisation valid throughout the European Union24/06/2013

Contact address:

Marklas Nederlands BV 
Beneluxlaan 2b 
3446 GR Woerden
The Netherlands

Product information

Product information

22/09/2016  Stayveer -EMEA/H/C/002644 -PSUSA/425/201511

Name Language First published Last updated
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - Product Information SV = svenska 2013-07-02 2016-10-12

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.


Name Language First published Last updated
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12
Stayveer : EPAR - All Authorised presentations SV = svenska 2013-07-02 2016-10-12

Pharmacotherapeutic group

Other antihypertensive drugs

Therapeutic indication

Treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity and symptoms in patients with World Health Organization (WHO) functional class III. Efficacy has been shown in:

  • primary (idiopathic and familial) PAH;
  • PAH secondary to scleroderma without significant interstitial pulmonary disease;
  • PAH associated with congenital systemic-to-pulmonary shunts and Eisenmenger’s physiology.

Some improvements have also been shown in patients with PAH WHO functional class II.

Stayveer is also indicated to reduce the number of new digital ulcers in patients with systemic sclerosis and ongoing digital-ulcer disease.

Assessment History

Changes since initial authorisation of medicine

Initial marketing-authorisation documents

Name Language First published Last updated
Stayveer : EPAR - Public assessment report SV = svenska 2013-07-02  
CHMP summary of positive opinion for Stayveer SV = svenska 2013-03-22  

Authorised

This medicine is approved for use in the European Union