Colistin combinations

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On 21 April 2016, the European Medicines Agency (the Agency) completed a review of the effectiveness of and antimicrobial resistance to all veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally. The Agency’s Committee for Medicinal Products for Veterinary Use (CVMP) concluded that the overall benefit-risk balance for the aforementioned products is negative, due to a lack of clinical relevance and in view of over-exposure of colistin that could pose a potential risk to animal and human health from an acceleration of the occurrence of colistin resistance. The CVMP recommended that all marketing authorisations for veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally should be withdrawn throughout the European Union (EU).

What is colistin?

Colistin belongs to the polymyxin group of antibiotics. Colistin is used for the treatment and prevention of diseases caused by sensitive bacteria (e.g. Escherichia coli) in pigs, poultry, rabbits, cattle, sheep and goats. Combinations of colistin with other antimicrobials are available for group treatments of gastro-intestinal and respiratory infections in food-producing animals in different European Member States. These include veterinary medicinal products containing combinations of colistin with14 different antimicrobial substances, belonging to different classes e.g. β-lactams, tetracyclines, macrolides, sulfonamides and trimethoprim (see Annex I on the 'All documents' tab).

Why were veterinary medicinal products containing colistin in combination with other antimicrobial substances reviewed?

Following a request from the European Commission, in July 2013 the CVMP and CHMP adopted scientific advice and detailed considerations on colistin1. This advice critically reviewed information on the use of colistin in food-producing animals in the EU, its effect on the development of resistance to this category of antimicrobial agents in bacterial species that are of importance for human and animal health and the possible impact on human and animal health.

In May 2014 the European Commission initiated a referral procedure under Article 35 of Directive 2001/82/EC for all veterinary medicinal products containing colistin as sole active substance for oral administration to food-producing species (EMEA/V/A/106). The procedure was concluded and on 16 March 2015 the European Commission adopted a Decision2 restricting the indications, target species, and duration of treatment of the concerned products, as well as adding prudent use warnings to the product information.

On 4 May 2015, the European Commission initiated a referral procedure under Article 35 of Directive 2001/82/EC for all veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally. The CVMP was requested to review the marketing authorisations and the available data in order to ensure responsible use of the substance in protecting animal health and limiting the possibility of future risk to public health.


1  Request for scientific advice on the impact on public health and animal health of the use of antibiotics in animals, answer to the first request from the European Commission (EMA/363834/2013) 
   Use of colistin products in animals within the European Union: development of resistance and possible impact on human and animal health (EMA/755938/2012) 

2 Commission Decision concerning, in the framework of Article 35 of Directive 2001/82/EC of the European Parliament and of the Council, the marketing authorisations for all veterinary medicinal products containing "Colistin" to be administered orally ((2015)1916 of 16/03/2015)

Which data has the CVMP reviewed?

Proprietary data, scientific references and expert reports were provided in this Article 35 referral procedure in support of some indications of some of the products included in the scope of the procedure. In addition, the marketing authorisation holders were asked to justify the benefits of using a colistin combination product over the use of monotherapy for the treatment of the respective conditions, particularly taking into account the CVMP guideline on pharmaceutical fixed combination products1 (EMEA/CVMP/83804/2005).


1CVMP guideline on pharmaceutical fixed combination products (EMEA/CVMP/83804/2005) 

What are the conclusions of the CVMP?

Based on the evaluation of the currently available data, the CVMP concluded that no benefit could be demonstrated when using colistin combination products instead of monotherapy and no feasible risk mitigation measures could be identified to address the identified potential risk for human health, as even limited use of colistin combination products was considered unnecessary. Therefore the CVMP recommended that all marketing authorisations for all veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally should be withdrawn.

The European Commission issued a decision on 14 July 2016.

Name Language First published Last updated
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally BG = bălgarski 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally ES = español 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally CS = čeština 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally DA = dansk 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally DE = Deutsch 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally ET = eesti keel 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally EL = elliniká 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally EN = English 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally FR = français 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally IT = italiano 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally LV = latviešu valoda 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally LT = lietuvių kalba 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally HU = magyar 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally MT = Malti 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally NL = Nederlands 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally PL = polski 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally PT = português 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally RO = română 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally SK = slovenčina 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally SL = slovenščina 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally FI = suomi 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally SV = svenska 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally HR = Hrvatski 2016-08-05  

Key facts

Approved nameColistin combinations
International non-proprietary name (INN) or common name

colistin and amoxicillin; ampicillin; chlortetracycline; doxycycline; enrofloxacin; erythromycin; neomycin; oxytetracycline; spiramycin; sulfadimethoxine; sulfaguanidine; sulfamethoxypyridazine ...

Associated namesPlease see Annex I
Class
Reference numberEMEA/V/A/111
TypeArticle 35
StatusEuropean Commission final decision
Opinion date21/04/2016
EC decision date14/07/2016

All documents

Name Language First published Last updated
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally BG = bălgarski 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally ES = español 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally CS = čeština 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally DA = dansk 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally DE = Deutsch 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally ET = eesti keel 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally EL = elliniká 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally EN = English 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally FR = français 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally IT = italiano 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally LV = latviešu valoda 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally LT = lietuvių kalba 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally HU = magyar 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally MT = Malti 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally NL = Nederlands 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally PL = polski 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally PT = português 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally RO = română 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally SK = slovenčina 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally SL = slovenščina 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally FI = suomi 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally SV = svenska 2016-08-05  
Questions and answers on veterinary medicinal products containing colistin in combination with other antimicrobial substances to be administered orally HR = Hrvatski 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III BG = bălgarski 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III ES = español 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III CS = čeština 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III DA = dansk 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III DE = Deutsch 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III ET = eesti keel 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III EL = elliniká 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III EN = English 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III FR = français 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III IT = italiano 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III LV = latviešu valoda 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III LT = lietuvių kalba 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III HU = magyar 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III MT = Malti 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III NL = Nederlands 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III PL = polski 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III PT = português 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III RO = română 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III SK = slovenčina 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III SL = slovenščina 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III FI = suomi 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III SV = svenska 2016-08-05  
Colistin combinations Article 35 referral - Annexes I, II, III HR = Hrvatski 2016-08-05  

Document description

  • Questions and answers (Q&A)- easy-to-understand summary of key issues and Committee conclusions
  • List of the medicines affected by the referral (annex I)
  • Scientific conclusions of the Committee (annex II)

The following two documents may not always be available:

  • Changes to the summary of product characteristics, labeling or package leaflet ('annex III') - available when changes have been recommended by the Committee
  • Conditions of the marketing authorisation (Annex IV) - available when the Committee recommends measures to be taken for the marketing authorisation(s) such as safety measures or extra studies

Current status:
European Commission final decision