Terpenic derivatives - referral

Current status

European Commission final decision

Overview

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.

Questions and answers on the review of suppositories containing terpenic derivatives

Adopted Reference Number: EMA/CHMP/763180/2011 Summary:

Outcome of a procedure under Article 31 of Directive 2001/83/EC as amended

Key facts

About this medicine

• Approved name:
  Terpenic derivatives
• International non-proprietary name (INN) or common name:
  • camphor
  • cineole
  • niaouli
  • wild thyme
  • terpineol
  • terpine
  • citral
  • menthol
  • essential oils of pine needle, eucalyptus and turpentine
• Class:
  Terpenic derivatives

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMA/CHMP/763180/2011
• 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.

Key dates and outcomes

• CHMP opinion date:
  17/11/2011
• EC decision date:
  20/01/2012

All documents

Terpenic derivatives - Article 31 referral - Assessment report

Adopted Reference Number: EMEA/H/A-1284

Terpenic derivatives - Article 31 referral - Annex I

Adopted Reference Number: EMEA/H/A-1284

Terpenic derivatives - Article 31 referral - Annex II

Adopted Reference Number: EMEA/H/A-1284

Terpenic derivatives - Article 31 referral - Annex III

Adopted Reference Number: EMEA/H/A-1284

Questions and answers on the review of suppositories containing terpenic derivatives

Adopted Reference Number: EMA/CHMP/763180/2011 Summary:

Outcome of a procedure under Article 31 of Directive 2001/83/EC as amended

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.