Codeine-containing medicines

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CMDh position
  • European Commission final decision
Current status:
Position provided by CMDh

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
Position provided by CMDh
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.

Decision making model
PRAC-CMDh
Authorisation model
Nationally authorised product(s)
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

  • Document description

    • Annex I - List of the medicines affected by the referral
    • Annex II - Scientific conclusions of the CHMP or 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 or CMDh assessment report - The assessment and conclusions of the PRAC and CHMP or CMDh on the issues investigated

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