Ambroxol and bromhexine-containing medicines

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Summary

  

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The recommendations were originally made by EMA’s Pharmacovigilance Risk Assessment Committee (PRAC), which confirmed the previously known risk of allergic reactions and also identified a small risk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

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.
More about the medicines

Ambroxol and bromhexine are mainly used by mouth as expectorants to help make the mucus thinner and therefore easier to be cleared away in patients with short- or long-term diseases of the lungs or airways.

For ambroxol, lozenge formulations are also available to relieve sore throat. Ambroxol formulations for injection are also used in premature and newborn babies to treat respiratory distress syndrome, a condition in which the baby’s lungs are too immature for the baby to breathe properly. Some of these injectable formulations are also used to increase lung development before birth. Injectable formulations are also used to prevent and treat lung complications following surgery.

Ambroxol- and bromhexine-containing medicines are marketed as single products or as fixed combination products with various other active ingredients. The majority of these medicines are available over the counter, whereas some are prescription-only medicines, depending on the condition to be treated and how the treatment is given.

As these medicines have been authorised via national procedures, approved uses are not the same in all EU countries.

Ambroxol and bromhexine medicines have been authorised in: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain and Sweden.

More about the procedure

The review of ambroxol and bromhexine was initiated on 4 April 2014 at the request of Belgium, under Article 31 of Directive 2001/83/EC.

The review was carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the Committee responsible for the evaluation of safety issues for human medicines, which made a set of recommendations. As ambroxol- and bromhexine-containing medicines are all authorised nationally, the PRAC recommendation was forwarded to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), for a position. The CMDh is a regulatory body representing EU Member States, and is responsible for ensuring harmonised safety standards for medicines authorised via national procedures across the EU.

The CMDh position was agreed by majority vote, and will now be sent to the European Commission for the adoption of an EU-wide legally binding decision.

Name Language First published Last updated
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated BG = bălgarski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated ES = español 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated CS = čeština 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated DA = dansk 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated DE = Deutsch 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated ET = eesti keel 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated EL = elliniká 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated EN = English 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated FR = français 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated IT = italiano 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated LV = latviešu valoda 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated LT = lietuvių kalba 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HU = magyar 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated MT = Malti 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated NL = Nederlands 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated PL = polski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated PT = português 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated RO = română 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated SK = slovenčina 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated SL = slovenščina 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated FI = suomi 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated SV = svenska 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05

Key facts

About this medicine

Approved nameAmbroxol and bromhexine-containing medicines
International non-proprietary name (INN) or common name

ambroxol and bromhexine

Associated names-
Class-

About this procedure

Current statusEuropean Commission final decision
Reference numberEMEA/H/A-31/1397
TypeArticle 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 modelPRAC-CMDh
Authorisation modelNationally authorised product(s)

Key dates and outcomes

Procedure start date10/04/2014
PRAC recommendation date10/09/2015
CHMP opinion/CMDh position date18/11/2015
EC decision date14/01/2016
OutcomeVariation

All documents

Procedure started

Name Language First published Last updated
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex I HR = Hrvatski 2014-04-11 2016-02-05
Ambroxol and bromhexine Article-31 referral - PRAC list of questions HR = Hrvatski 2014-04-11  
Ambroxol and bromhexine Article-31 referral - Notification HR = Hrvatski 2014-04-11  
Ambroxol and bromhexine Article-31 referral - Timetable for the procedure HR = Hrvatski 2014-04-11 2014-12-05
Ambroxol and bromhexine Article-31 referral - Review started HR = Hrvatski 2014-04-11 2014-04-30

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Name Language First published Last updated
Ambroxol and bromhexine Article-31 referral - PRAC considers risk of severe allergic reactions with ambroxol- and bromhexine-containing medicines to be small HR = Hrvatski 2015-01-12  
Ambroxol and bromhexine Article-31 referral - PRAC assessment report HR = Hrvatski 2015-03-10 2015-12-02

Position provided by CMDh

Name Language First published Last updated
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Ambroxol and bromhexine expectorants: safety information to be updated HR = Hrvatski 2015-02-27 2016-02-05

European Commission final decision

Name Language First published Last updated
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex II HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Divergent opinion (Croatia) HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Annex III HR = Hrvatski 2015-02-27 2016-02-05
Ambroxol and bromhexine Article-31 referral - Divergent opinion (Netherlands) HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Divergent opinion (France) HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Divergent opinion (Germany, Hungary, Latvia) HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Divergent opinion (Italy) HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Divergent opinion (Belgium, Luxembourg) HR = Hrvatski 2016-02-05  
Ambroxol and bromhexine Article-31 referral - Divergent opinion (Portugal, Czech Republic) HR = Hrvatski 2016-02-05  

Document description:

  • Annex I - List of the medicines affected by the referral
  • Annex II - Scientific conclusions of the Committee for Medicinal Products for Human Use (CHMP) or Coordination Group for Mutual Recognition and Decentralised Procedures - Human (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 / CMDh assessment report - The assessment and conclusions of the PRAC and CHMP or CMDh on the issues investigated

Current status:
European Commission final decision

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