Ambroxol and bromhexine-containing medicines

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CMDh position
  • European Commission final decision
Current status:
European Commission final decision

Overview

 

Ambroxol and bromhexine expectorants: safety information to be updated

Risk of allergy and skin reactions to be included in the product information

The CMDh1 has endorsed by majority vote recommendations to update the product information for ambroxol- and bromhexine-containing medicines with information about the small risk of severe allergic reactions and severe cutaneous adverse reactions (SCARs). The medicines are widely available in the EU for use as expectorants (to help clear mucus from the airways).

The recommendations were originally made by EMA's Pharmacovigilance Risk Assessment Committee (PRAC), which confirmed the previously known risk of allergic reactions and also identified a small risk of SCARs, a group of skin conditions which include erythema multiforme and Stevens-Johnson syndrome.

As a result, SCARs are now to be listed as side effects in the product information for these medicines, and patients are to stop treatment immediately if symptoms of SCARs occur. Reports of severe allergic reactions and SCARs in patients taking the medicines are rare, and the frequencies of these side effects are unknown.

In making the recommendations, the PRAC evaluated available data on ambroxol and bromhexine, including reports of severe allergic reactions or SCARs.

As the CMDh position was adopted by majority vote, the CMDh position will now be sent to the European Commission, which will take an EU-wide legally binding decision.

Information to patients

  • There is a small risk of allergy and skin reactions with ambroxol and bromhexine used as expectorants to clear mucus in the airways.
  • If you experience skin reactions such as skin swellings or rash, stop treatment immediately and contact your doctor.
  • If you are taking ambroxol or bromhexine and have any questions or concerns speak to your doctor of pharmacist.

Information to healthcare professionals

  • Anaphylactic reactions and severe cutaneous adverse reactions (SCARs), including erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis and acute generalised exanthematous pustulosis, have been reported in patients receiving ambroxol.
  • As ambroxol is a metabolite of bromhexine, the risk of anaphylactic and severe cutaneous reactions is considered to apply also to bromhexine.
  • The risk of anaphylactic reactions and SCARs with ambroxol or bromhexine is low. Frequencies of these side effects are unknown.
  • Advise your patients that they should stop treatment immediately if symptoms of progressive skin rash occur.

1 The CMDh is a medicines regulatory body representing the European Union (EU) Member States.

Key facts

About this medicine
Approved name
Ambroxol and bromhexine-containing medicines
International non-proprietary name (INN) or common name
  • ambroxol
  • bromhexine
Class
-
About this procedure
Current status
European Commission final decision
Reference number
EMEA/H/A-31/1397
Type
Article 31 referrals

This type of referral is triggered when the interest of the Union 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
10/04/2014
PRAC recommendation date
10/09/2015
CHMP opinion/CMDh position date
18/11/2015
EC decision date
14/01/2016
Outcome
Variation

All documents

Procedure started

  • List item

    Ambroxol and bromhexine Article-31 referral - Review started (PDF/70.12 KB)


    First published: 11/04/2014
    Last updated: 30/04/2014
    EMA/203011/2014 corr. 1

  • List item

    Ambroxol and bromhexine Article-31 referral - Notification (PDF/46.58 KB)


    First published: 11/04/2014
    Last updated: 11/04/2014

  • List item

    Ambroxol and bromhexine Article-31 referral - Timetable for the procedure (PDF/71.87 KB)


    First published: 11/04/2014
    Last updated: 05/12/2014
    EMA/PRAC/189079/2014

  • List item

    Ambroxol and bromhexine Article-31 referral - Annex I (PDF/889.36 KB)


    First published: 11/04/2014
    Last updated: 05/02/2016
    EMA/223489/2014 – corr.1

  • List item

    Ambroxol and bromhexine Article-31 referral - PRAC list of questions (PDF/85.37 KB)


    First published: 11/04/2014
    Last updated: 11/04/2014
    EMA/PRAC/189078/2014

  • Recommendation provided by Pharmacovigilance Risk Assessment Committee

    Position provided by CMDh

  • List item

    Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated (PDF/87.4 KB)

    Adopted

    First published: 27/02/2015
    Last updated: 05/02/2016
    EMA/130676/2015

  • List item

    Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated (PDF/87.4 KB)

    Adopted

    First published: 27/02/2015
    Last updated: 05/02/2016
    EMA/130676/2015

  • European Commission final decision

  • List item

    Ambroxol and bromhexine Article-31 referral - Divergent opinion (Belgium, Luxembourg) (PDF/51.63 KB)


    First published: 05/02/2016
    Last updated: 05/02/2016

  • List item

    Ambroxol and bromhexine Article-31 referral - Annex II (PDF/52.15 KB)


    First published: 05/02/2016
    Last updated: 05/02/2016

  • List item

    Ambroxol and bromhexine Article-31 referral - Divergent opinion (Croatia) (PDF/56.1 KB)


    First published: 05/02/2016
    Last updated: 05/02/2016

  • List item

    Ambroxol and bromhexine Article-31 referral - Divergent opinion (Portugal, Czech Republic) (PDF/61.02 KB)


    First published: 05/02/2016
    Last updated: 05/02/2016

  • List item

    Ambroxol and bromhexine Article-31 referral - Divergent opinion (France) (PDF/50.9 KB)


    First published: 05/02/2016
    Last updated: 05/02/2016

  • List item

    Ambroxol and bromhexine Article-31 referral - Divergent opinion (Italy) (PDF/49.09 KB)


    First published: 05/02/2016
    Last updated: 05/02/2016

  • List item

    Ambroxol and bromhexine Article-31 referral - Divergent opinion (Germany, Hungary, Latvia) (PDF/52.64 KB)


    First published: 05/02/2016
    Last updated: 05/02/2016

  • List item

    Ambroxol and bromhexine Article-31 referral - Divergent opinion (Netherlands) (PDF/42.01 KB)


    First published: 05/02/2016
    Last updated: 05/02/2016

  • List item

    Ambroxol and bromhexine Article-31 referral - Annex III (PDF/43.77 KB)


    First published: 27/02/2015
    Last updated: 05/02/2016

  • Description of documents published

    Please note that some of the listed documents apply only to certain procedures.

    • Overview - lay-language summary of the stage of the procedure
    • Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
    • Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
    • List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
    • Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
    • List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
    • List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
    • Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
    • Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
    • Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
    • Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
    • Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
    • Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
    • Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
    • Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)

    Note that older documents may have different titles.

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