Codeine-containing medicines

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CMDh final position
Current status
CMDh final position

Overview


Restrictions on use of codeine for pain relief in children – CMDh endorses PRAC recommendation

The Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) has endorsed by consensus a series of risk-minimisation measures to address safety concerns with codeine-containing medicines when used for the management of pain in children. Codeine is an opioid that is authorised as a painkiller in adults and children. The effect of codeine on pain is due to its conversion into morphine in the patient's body.

This follows a review of these medicines by the European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC), which investigated reports of serious and fatal respiratory depression in children after taking codeine for pain relief. Most of the cases occurred after surgical removal of the tonsils or adenoids for obstructive sleep apnoea (frequent interruption of breathing during sleep).

Some of the children who had suffered severe side effects had evidence of being 'ultra-rapid metabolisers' of codeine. In these patients, codeine is converted into morphine in the body at a faster rate than normal, resulting in high levels of morphine in the blood that can cause toxic effects such as respiratory depression.

The PRAC concluded that a number of risk-minimisation measures are necessary to ensure that only children for whom the benefits are greater than the risks are given the medicine for pain relief. The CMDh agreed with the PRAC's conclusions and endorsed the following recommendations:

  • Codeine-containing medicines should only be used to treat acute (short-lived) moderate pain in children above 12 years of age, and only if it cannot be relieved by other painkillers such as paracetamol or ibuprofen, because of the risk of respiratory depression associated with codeine use.
  • Codeine should not be used at all in children (aged below 18 years) who undergo surgery for the removal of the tonsils or adenoids to treat obstructive sleep apnoea, as these patients are more susceptible to respiratory problems.
  • The product information of these medicines should carry a warning that children with conditions associated with breathing problems should not use codeine.

The risk of side effects with codeine may also apply to adults. Codeine should therefore not be used in people of any age who are known to be ultra-rapid metabolisers nor in breastfeeding mothers (because codeine can pass to the baby through breast milk). The product information for codeine should also include general information for healthcare professionals, patients and carers on the risk of morphine side effects with codeine, and how to recognise their symptoms.

As the PRAC recommendation was endorsed by consensus by the CMDh, it will now be implemented directly by all Member States, according to an agreed timetable.

Key facts

About this medicine
Approved name
Codeine-containing medicines
International non-proprietary name (INN) or common name
codeine
Class
-
About this procedure
Current status
CMDh final position
Reference number
EMEA/H/A-31/1342
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.

Authorisation model
Nationally authorised product(s)
Decision making model
PRAC-CMDh
Key dates and outcomes
Procedure start date
03/10/2012
PRAC recommendation date
13/06/2013
CHMP opinion/CMDh position date
26/06/2013
Outcome
Risk minimisation measures

All documents

Procedure started

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Position provided by CMDh

  • List item

    Codeine Article-31 referral - Restrictions on use of codeine for pain relief in children – CMDh endorses PRAC recommendation (PDF/82.62 KB)


    First published: 28/06/2013
    Last updated: 02/08/2013
    EMA/385716/2013

  • List item

    Codeine Article-31 referral - Annex IV (PDF/20.64 KB)


    First published: 02/08/2013
    Last updated: 02/08/2013

  • List item

    Codeine Article-31 referral - Annex I (PDF/930.18 KB)


    First published: 02/08/2013
    Last updated: 02/08/2013

  • List item

    Codeine Article-31 referral - Annex II (PDF/59.5 KB)


    First published: 02/08/2013
    Last updated: 02/08/2013

  • List item

    Codeine Article-31 referral - Annex III (PDF/83.63 KB)


    First published: 02/08/2013
    Last updated: 02/08/2013

  • List item

    Codeine Article-31 referral - Restrictions on use of codeine for pain relief in children – CMDh endorses PRAC recommendation (PDF/82.62 KB)


    First published: 28/06/2013
    Last updated: 02/08/2013
    EMA/385716/2013

  • 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.

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