Ibuprofen- and dexibuprofen-containing medicines

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

Overview

Updated advice on use of high‑dose ibuprofen

Review confirms small cardiovascular risk with daily doses at or above 2,400 mg

The CMDh1 has endorsed by consensus updated advice on the use of high-dose ibuprofen. This follows a review carried out by EMA's Pharmacovigilance Risk Assessment Committee (PRAC), which confirmed a small increased risk of cardiovascular problems, such as heart attacks and strokes, in patients taking high doses of ibuprofen (at or above 2,400 mg per day). The review clarifies that the risk with high-dose ibuprofen is similar to the risk seen with some other non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors and diclofenac.

No increase in cardiovascular risk is seen with ibuprofen at doses of up to 1,200 mg per day, which is the highest dose generally used for over-the-counter (OTC) preparations taken by mouth in the European Union (EU).

To minimise the cardiovascular risk, high doses of ibuprofen (2,400 mg per day or higher) should be avoided in patients with serious underlying heart or circulatory conditions, such as heart failure, heart disease and circulatory problems or in those who have previously had a heart attack or stroke.

In addition, doctors should carefully assess a patient's risk factors for heart or circulatory conditions before initiating long-term treatment with ibuprofen, particularly if high doses are required. Risk factors include smoking, high blood pressure, diabetes and high blood cholesterol.

The review also looked at data on the interaction between ibuprofen and low-dose aspirin when the latter is taken to reduce the risk of heart attacks and strokes. Laboratory studies have shown that ibuprofen reduces the blood-thinning effects of aspirin. However, it remains uncertain whether long-term use of ibuprofen in clinical practice reduces the benefits of low-dose aspirin in preventing heart attacks and strokes. Occasional use of ibuprofen should not affect the benefits of low-dose aspirin.

The updated advice on the cardiovascular risk of high-dose ibuprofen will be included in the product information of ibuprofen medicines, along with information on the interaction between ibuprofen and aspirin.

The recommendations for ibuprofen also apply to dexibuprofen, a medicine similar to ibuprofen. A high dose of dexibuprofen is a dose at or above 1,200 mg per day.


1 The CMDh is a medicines regulatory body representing the European Union (EU) Member States, Iceland, Liechtenstein and Norway.

Key facts

About this medicine
Approved name
Ibuprofen- and dexibuprofen-containing medicines
International non-proprietary name (INN) or common name
ibuprofen and dexibuprofen
About this procedure
Current status
Position provided by CMDh
Reference number
EMEA/H/A-31/1401
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
13/06/2014
PRAC recommendation date
10/04/2015
CHMP opinion/CMDh position date
20/05/2015
Outcome
Variation

All documents

Procedure started

  • List item

    Ibuprofen and dexibuprofen Article-31 referral - Annex I (PDF/2.57 MB)


    First published: 20/06/2014
    Last updated: 20/06/2014
    EMA/373842/2014

  • List item

    Ibuprofen and dexibuprofen Article-31 referral - Review started (PDF/67.49 KB)


    First published: 13/06/2014
    Last updated: 13/06/2014
    EMA/348597/2014

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    Ibuprofen and dexibuprofen Article-31 referral - Timetable for the procedure (PDF/71.02 KB)


    First published: 13/06/2014
    Last updated: 16/03/2015
    EMA/PRAC/332908/2014 Rev. 2

  • List item

    Ibuprofen and dexibuprofen Article-31 referral - PRAC list of questions (PDF/113.43 KB)

    Adopted

    First published: 13/06/2014
    Last updated: 13/06/2014
    EMA/PRAC/332909/2014

  • List item

    Ibuprofen and dexibuprofen Article-31 referral - Notification (PDF/21.57 KB)


    First published: 13/06/2014
    Last updated: 13/06/2014

  • Recommendation provided by Pharmacovigilance Risk Assessment Committee

    Position provided by CMDh

  • List item

    Ibuprofen and dexibuprofen Article-31 referral - Updated advice on use of high-dose ibuprofen (PDF/86.6 KB)

    Adopted

    First published: 22/05/2015
    Last updated: 22/05/2015
    EMA/325007/2015

  • List item

    Ibuprofen and dexibuprofen Article-31 referral - Assessment report (PDF/1.01 MB)

    Adopted

    First published: 14/07/2015
    Last updated: 14/07/2015
    EMA/348171/2015

  • List item

    Ibuprofen and dexibuprofen Article-31 referral - Annex IV (PDF/25.81 KB)


    First published: 14/07/2015
    Last updated: 14/07/2015

  • List item

    Ibuprofen and dexibuprofen Article-31 referral - Updated advice on use of high-dose ibuprofen (PDF/86.6 KB)

    Adopted

    First published: 22/05/2015
    Last updated: 22/05/2015
    EMA/325007/2015

  • List item

    Ibuprofen and dexibuprofen Article-31 referral - Annex III (PDF/46.35 KB)


    First published: 22/05/2015
    Last updated: 22/05/2015

  • 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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