Review of short-acting beta-agonists started
The European Medicines Agency has started a review of medicines called ‘short-acting beta-agonists’, to assess their safety and effectiveness when used to suppress premature labour.
Short-acting beta-agonists are widely used in Europe to treat asthma, and are usually taken by inhalation using an inhaler device. They relax the smooth muscles, which are found in many organs including on the inner linings of the airways, causing the airways to widen and making it easier to breathe. However, in several European countries, certain short-acting beta-agonists are also approved as ‘tocolytics’ (medicines that suppress labour contractions) for use in premature labour, since they relax the smooth muscles in the womb. When used for this purpose, they are usually given by injection or as tablets or suppositories, and at higher doses than those used to treat asthma.
Due to the higher doses, there is a known risk of cardiovascular side effects (problems affecting the heart and blood vessels) with these medicines when they are used to suppress premature labour. As a result, the prescribing information contains safety warnings and the medicines must not be used in patients with a history or a risk of cardiovascular disease. Moreover, there is uncertainty about the effectiveness of prolonged use of these medicines (for more than 48 hours) to prevent premature labour. Therefore, concerns have been raised about the benefit of using these medicines as tocolytics compared with the risk of cardiovascular side effects.
The European Medicines Agency will evaluate the latest available evidence on the benefit-risk balance of short-acting beta-agonists when these medicines are used for stopping premature labour in pregnant women.
More about the medicine
Short-acting beta-agonists have been authorised by national procedures in several European Union (EU) Member States and have been marketed for several years under various trade names. The medicines included in the EU review are fenoterol, hexoprenaline, isoxsuprine, ritodrine, salbutamol and terbutaline, which are authorised for tocolytic treatment. They are available as solutions for injection or infusion, tablets, oral solutions and suppositories.
Short-acting beta-agonists work by stimulating a receptor on the surface of cells called the ‘beta-2 adrenergic receptor’, which brings about smooth muscle relaxation. They are called ‘short acting’ because they work quickly, usually having an effect in less than five minutes and lasting for several hours. Smooth muscles are found in many organs of the body including on the inner linings of the blood vessels, stomach and gut, and reproductive organs.
More about the procedure
The review of short-acting beta-agonists has been initiated at the request of the Hungarian medicines agency, under Article 31 of Directive 2001/83/EC.
The review is being carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the Committee responsible for the evaluation of safety issues for human medicines, which will make a set of recommendations. As short-acting beta-agonists are all authorised nationally, the PRAC recommendation will be forwarded to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which is a regulatory body that represents national medicines regulatory authorities of the EU Member States. This will result in harmonised measures to be implemented in all Member States.
A previous review was carried out in 2006 by the former Pharmacovigilance Working Party of the European Medicines Agency, to consider the risk of myocardial ischaemia (reduced blood supply to the heart muscle) with short-acting beta-agonists. This led to the existing warnings and contraindication being included in the prescribing information for these medicines with regard to their use as tocolytics.
|Name||Language||First published||Last updated|
|Short-acting beta-agonists Article 31 referral - Review of short-acting beta-agonists started||(English only)||30/11/2012|
About this medicine
|Approved name||Short-acting beta-agonists|
|International non-proprietary name (INN) or common name|
terbutaline, salbutamol, hexoprenaline, ritodrine, fenoterol, isoxsuprine
About this procedure
|Current status||Under evaluation|
|Type||Article 31 referrals|
This type of referral is triggered when the interest of the Community is involved, following concerns relating to the quality, safety or efficacy of a medicine or a class of medicines.
|Decision making model||PRAC-CMDh|
|Authorisation model||Nationally authorised product(s)|
Key dates and outcomes
|Procedure start date||27/11/2012|
|Name||Language||First published||Last updated|
|Short-acting beta-agonists Article 31 referral - Notification||EN = English||30/11/2012|
|Short-acting beta-agonists Article 31 referral - PRAC list of questions||EN = English||30/11/2012|
|Short-acting beta-agonists Article 31 referral - Review of short-acting beta-agonists started||EN = English||30/11/2012|
|Short-acting beta-agonists Article 31 referral - Timetable for the procedure||EN = English||30/11/2012||17/05/2013|
|Short-acting beta-agonists Article 31 referral - Annex I||EN = English||30/11/2012||10/01/2013|
- Questions and answers - Easy-to-understand summary of the key issues and conclusions
- Annex I - List of the medicines affected by the referral
- Annex II - Scientific conclusions of the CHMP or CMDh
- Annex III - Changes to the summary of product characteristics, labelling or package leaflet - available when the CHMP or CMDh recommends changes to the product information. Also includes conditions for lifting of suspensions, if applicable
- Annex IV - Conditions of the marketing authorisation - available when the CHMP or CMDh recommends other measures to be taken for the marketing authorisation such as safety measures or additional studies
- Notification - A letter from a Member State, the European Commission or a marketing-authorisation holder requesting the initiation of a referral procedure
- Rationale for triggering - Background provided by the party triggering the referral explaining the issues leading to the initiation of the procedure
- PRAC list of questions - Questions agreed by the PRAC requesting further information to evaluate the issues identified
- PRAC timetable - Timeframe agreed by the PRAC to receive information, assess the issues and adopt a recommendation
- PRAC / CHMP or CMDh assessment report - The assessment and conclusions of the PRAC and CHMP or CMDh on the issues investigated