Terpenic derivatives

  • Email
  • Help

The European Medicines Agency has completed a review of the safety and effectiveness of suppositories containing terpenic derivatives. The Agency’s Committee for Medicinal Products for Human Use (CHMP) has concluded that the use of these medicines should be contraindicated in children under 30 months old, children with a history of epilepsy or febrile convulsion and children with a recent history of anorectal lesion (precancerous growths in the anus or rectum).

What are suppositories containing terpenic derivatives?

Suppositories containing terpenic derivatives are medicines given rectally used to treat various conditions. The medicines concerned by this review are used to treat coughs and colds in children and adolescents. The approved indications vary in different European Union (EU) countries, but typically include supportive treatment for mild, sudden bronchial disorders, particularly productive and non-productive cough.

Terpenic derivatives are mainly obtained from natural substances originating from plants such as conifers. They include camphor, cineole, terpineol, terpine, citral and menthol. They are often found in herbal substances and herbal preparations, such as pine needle or turpentine. They are also found in essential oils obtained from plants, such as niaouli, wild thyme or eucalyptus.

Medicines containing terpenic derivatives are available in various forms, including solutions to be inhaled or rubbed into the skin as well as suppositories. In the EU, suppositories containing terpenic derivatives are authorised by national procedures and are available without prescription. They are currently marketed in Belgium, France, Luxembourg, Finland, Italy, Portugal and Spain under various trade names.

Why were suppositories containing terpenic derivatives reviewed?

The French medicines regulatory agency had concerns about the safety of suppositories containing terpenic derivatives, particularly the risk of serious neurological side effects in young children such as convulsions. The French agency was also concerned that reliable data on the effectiveness of these medicines were not available, and that the medicines did not fulfil the latest clinical recommendations for treating cough in children.

Consequently, on 27 October 2010 the French agency asked the CHMP to carry out a full assessment of the benefit-risk balance of suppositories containing terpenic derivatives in children younger than 30 months of age and to issue an opinion on whether the marketing authorisations for these medicines should be maintained, varied, suspended or withdrawn across the EU in this population.

Which data has the CHMP reviewed?

The CHMP looked at the benefit-risk assessment carried out by France, and information requested from the companies that market suppositories containing terpenic derivatives in the EU. This included study data supporting the marketing authorisations and safety data including reports of side effects from post-marketing surveillance and the published literature.

What are the conclusions of the CHMP?

Based on the evaluation of the currently available data and the scientific discussion within the Committee, the CHMP concluded that there was a risk of these medicines inducing neurological disorders, especially convulsions, in infants and small children. The CHMP noted that children aged up to 30 months and children with a history of epilepsy or febrile convulsion were most at risk of these neurological side effects because their nervous system is not yet fully developed. It also decided that there was a risk of these medicines causing local anorectal lesions.

The Committee noted that the effectiveness of these medicines had not been clearly demonstrated, as no clinical trials with suppositories containing terpenic derivatives had been performed and there were no studies focused on infants and children.

The Committee therefore recommended that the use of suppositories containing terpenic derivatives be contraindicated in children under 30 months old, children with a history of epilepsy or febrile convulsion and children with a recent history of anorectal lesion.

What are the recommendations for patients and carers?
  • Suppositories containing terpenic derivatives should not be used in children under 30 months old, children with a history of epilepsy or febrile convulsion and children with a recent history of anorectal lesion.
  • Terpenic derivatives in other forms, such as solutions to be inhaled or rubbed into the skin, may continue to be used as currently approved.
  • Patients and carers who have any questions should speak to their doctor or pharmacist.

The European Commission issued a decision on 20 January 2012.

Name Language First published Last updated
Questions and answers on the review of suppositories containing terpenic derivatives BG = bălgarski 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives ES = español 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives CS = čeština 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives DA = dansk 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives DE = Deutsch 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives ET = eesti keel 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives EL = elliniká 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives EN = English 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives FR = français 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives IT = italiano 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives LV = latviešu valoda 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives LT = lietuvių kalba 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives HU = magyar 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives MT = Malti 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives NL = Nederlands 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives PL = polski 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives PT = português 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives RO = română 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives SK = slovenčina 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives SL = slovenščina 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives FI = suomi 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives SV = svenska 2011-09-23 2012-04-13

Key facts

Approved nameTerpenic derivatives
International non-proprietary name (INN) or common name

camphor, cineole, niaouli, wild thyme, terpineol, terpine, citral, menthol and essential oils of pine needle, eucalyptus and turpentine

Associated names
ClassTerpenic derivatives
Reference numberEMA/CHMP/763180/2011
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.

StatusEuropean Commission final decision
Opinion date17/11/2011

All documents

Name Language First published Last updated
Questions and answers on the review of suppositories containing terpenic derivatives BG = bălgarski 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives ES = español 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives CS = čeština 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives DA = dansk 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives DE = Deutsch 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives ET = eesti keel 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives EL = elliniká 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives EN = English 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives FR = français 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives IT = italiano 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives LV = latviešu valoda 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives LT = lietuvių kalba 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives HU = magyar 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives MT = Malti 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives NL = Nederlands 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives PL = polski 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives PT = português 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives RO = română 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives SK = slovenčina 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives SL = slovenščina 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives FI = suomi 2011-09-23 2012-04-13
Questions and answers on the review of suppositories containing terpenic derivatives SV = svenska 2011-09-23 2012-04-13
Terpenic derivatives - Article 31 referral - Assessment report (English only) 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I BG = bălgarski 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I ES = español 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I CS = čeština 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I DA = dansk 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I DE = Deutsch 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I ET = eesti keel 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I EL = elliniká 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I EN = English 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I FR = français 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I IT = italiano 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I LV = latviešu valoda 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I LT = lietuvių kalba 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I HU = magyar 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I MT = Malti 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I NL = Nederlands 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I PL = polski 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I PT = português 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I RO = română 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I SK = slovenčina 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I SL = slovenščina 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I FI = suomi 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex I SV = svenska 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II BG = bălgarski 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II ES = español 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II CS = čeština 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II DA = dansk 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II DE = Deutsch 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II ET = eesti keel 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II EL = elliniká 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II EN = English 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II FR = français 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II IT = italiano 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II LV = latviešu valoda 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II LT = lietuvių kalba 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II HU = magyar 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II MT = Malti 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II NL = Nederlands 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II PL = polski 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II PT = português 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II RO = română 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II SK = slovenčina 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II SL = slovenščina 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II FI = suomi 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex II SV = svenska 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III BG = bălgarski 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III ES = español 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III CS = čeština 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III DA = dansk 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III DE = Deutsch 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III ET = eesti keel 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III EL = elliniká 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III EN = English 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III FR = français 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III IT = italiano 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III LV = latviešu valoda 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III LT = lietuvių kalba 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III HU = magyar 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III MT = Malti 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III NL = Nederlands 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III PL = polski 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III PT = português 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III RO = română 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III SK = slovenčina 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III SL = slovenščina 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III FI = suomi 2012-02-08  
Terpenic derivatives - Article 31 referral - Annex III SV = svenska 2012-02-08  

Document description

  • Questions and answers (Q&A) - easy-to-understand summary of key issues and Committee conclusions
  • Summary of Opinion - contains the CHMP opinion of the referred medicine(s)
  • List of the medicines affected by the referral (Annex I)
  • Scientific conclusions of the Committee (Annex II)

The following two documents are sometimes available:

  • Changes to the summary of product characteristics, labeling or package leaflet (also known as Annex III) - available when changes have been recommended by the Committee
  • Conditions of the marketing authorisation (also known as 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

Related information