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The recommendations were originally made by EMA's Pharmacovigilance Risk Assessment Committee (PRAC), which confirmed the previously known risk of allergic reactions and also identified a small risk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 and 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

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    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

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    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

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    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

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


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

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    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

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


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

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


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

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    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

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


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

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


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

  • Document description

    • 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

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