Diclofenac-containing medicines

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

Overview

New safety advice for diclofenac

New measures aim to minimise cardiovascular risks

On 28 June 2013, the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) endorsed by majority new safety advice for diclofenac-containing medicines that are given by means such as capsules, tablets, suppositories or injections, intended to have an effect on the whole body (known as a systemic effect). The new advice aims to minimise the risks of effects on the heart and circulation from these medicines.

This followed a review by the European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC) which found that the effects of systemic diclofenac on the heart and circulation are similar to those of selective COX-2 inhibitors, another group of painkillers. This applies particularly when diclofenac is used at a high dose and for long-term treatment. The PRAC therefore recommended that the same precautions already in place to minimise the risks of blood clots in the arteries with selective COX-2 inhibitors should be applied to diclofenac.

The CMDh agreed with the PRAC conclusion that although the benefits of systemic diclofenac still outweigh the risks, those risks were similar to the risks with COX-2 inhibitors, and it endorsed the recommendation that similar precautions should be applied.

The CMDh position was sent to the European Commission, which confirmed it and took a final legally binding decision throughout the EU on 25 September 2013.

Diclofenac is a widely used medicine for relieving pain and inflammation, particularly in painful conditions such as arthritis. It belongs to a group of medicines called 'non-steroidal anti-inflammatory drugs' (NSAIDs). The safety of NSAIDs has been closely monitored by regulatory authorities in the EU. Reviews of these medicines carried out in 2005, 2006 and 2012 have confirmed that NSAIDs as a class are associated with a small increased risk of arterial thromboembolic events (blood clots in the arteries) especially in patients with underlying heart or circulatory conditions or with certain cardiovascular risk factors, which in some cases has led to heart attack or stroke, particularly if used at high dose and for long periods.

A class warning of this risk is in place and the product information for all NSAIDs recommends that these medicines be used at the lowest effective dose for the shortest period of time necessary to control symptoms. As the risk is known to be somewhat higher with the subgroup of NSAIDs known as selective COX-2 inhibitors, increased measures to minimise risk are recommended in their product information.

The PRAC review of diclofenac was started at the request of the UK medicines regulatory agency, the MHRA, in October 2012 in response to findings from the 2012 review of NSAIDs. The latter identified a small increased risk of these cardiovascular side effects with diclofenac compared with other NSAIDs - an increase similar to that seen with the COX-2 inhibitors. The cardiovascular risk with any NSAID depends on a person's underlying risk factors, such as high blood pressure and cholesterol levels and also any underlying heart or circulatory conditions. About 8 people in 1,000 at moderate risk of heart disease are likely to have a heart attack over one year. The overall number of heart attacks in people at moderate risk would be expected to increase by around 3 cases per year for every 1,000 people treated with diclofenac (to 11 per 1,000 people per year).

Key facts

About this medicine
Approved name
Diclofenac-containing medicines
International non-proprietary name (INN) or common name
diclofenac
Class
Non-steroidal anti-inflammatory drugs (NSAIDs)
About this procedure
Current status
European Commission final decision
Reference number
EMEA/H/A-31/1344
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
31/10/2012
PRAC recommendation date
13/06/2013
CHMP opinion/CMDh position date
26/06/2013
EC decision date
25/09/2013
Outcome
Risk minimisation measures

All documents

Procedure started

  • List item

    Diclofenac Article-31 referral - Timetable for the procedure (PDF/61.26 KB)


    First published: 31/10/2012
    Last updated: 17/05/2013
    EMA/PRAC/696496/2012

  • List item

    Diclofenac Article-31 referral - Notification (PDF/554.29 KB)


    First published: 31/10/2012
    Last updated: 31/10/2012

  • List item

    Diclofenac Article-31 referral - Review started (PDF/65.21 KB)


    First published: 31/10/2012
    Last updated: 31/10/2012
    EMA/693599/2012

  • List item

    Diclofenac Article-31 referral - Annex I (PDF/2.51 MB)

    Draft

    First published: 31/10/2012
    Last updated: 27/11/2013
    EMA/704684/2012 Rev. 1

  • List item

    Diclofenac Article-31 referral - PRAC list of questions (PDF/74.94 KB)


    First published: 31/10/2012
    Last updated: 31/10/2012
    EMA/PRAC/696495/2012

  • Recommendation provided by Pharmacovigilance Risk Assessment Committee

    Position provided by CMDh

  • List item

    Diclofenac Article-31 referral - Divergent position to CMDh position (PDF/24.19 KB)


    First published: 27/11/2013
    Last updated: 27/11/2013
    EMEA/H/A-31/1344

  • List item

    Diclofenac Article-31 referral - Annex III (PDF/24.61 KB)


    First published: 27/11/2013
    Last updated: 27/11/2013
    EMEA/H/A-31/1344

  • List item

    Diclofenac Article-31 referral - Annex II (PDF/45.64 KB)


    First published: 27/11/2013
    Last updated: 27/11/2013
    EMEA/H/A-31/1344

  • List item

    Diclofenac Article-31 referral - New safety advice for diclofenac – CMDh endorses PRAC recommendation (PDF/82.93 KB)


    First published: 28/06/2013
    Last updated: 28/06/2013
    EMA/380947/2013

  • European Commission final decision

  • List item

    Diclofenac Article-31 referral - New safety advice for diclofenac (PDF/83.89 KB)


    First published: 27/11/2013
    Last updated: 27/11/2013
    EMEA/H/A-31/1344

  • List item

    Diclofenac Article-31 referral - New safety advice for diclofenac (PDF/83.89 KB)


    First published: 27/11/2013
    Last updated: 27/11/2013
    EMEA/H/A-31/1344

  • 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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