Flupirtine-containing medicines

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

Overview

Restrictions in the use of flupirtine-containing medicines

On 26 June 2013, the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) endorsed by majority new recommendations to restrict the use of oral flupirtine medicines and suppositories. These medicines should only be used for treating acute (short-term) pain in adults who cannot use other painkillers, such as non-steroidal anti-inflammatory drug (NSAIDs) and weak opioids, and treatment should not last longer than 2 weeks.

In addition, patients' liver function should be checked after each full week of treatment and treatment should be stopped if the patient has any signs of liver problems. Flupirtine must also not be used in patients with pre-existing liver disease or alcohol abuse problems or in patients taking other medicines known to cause liver problems.

The recommendations follow a review by the EMA's Pharmacovigilance Risk Assessment Committee (PRAC) which looked into reported liver problems with flupirtine, ranging from high liver-enzyme levels to liver failure. The PRAC evaluated the available data on liver safety, noting that there were no cases of liver failure or liver transplantation reported in patients who took the medicine for 2 weeks or less. The PRAC also reviewed the available data on the benefits of flupirtine and concluded that, while there were data from studies in the treatment of acute pain, there were insufficient data to support its use in the treatment of long-term pain.

In addition to oral medicines and suppositories, this review also covered injectable flupirtine medicines which were being given as a single injection for pain following surgery. The PRAC concluded that the benefits of injectable flupirtine continue to outweigh their risks when used in this way. Doctors using the injectable flupirtine should also follow relevant advice to minimise risk to patients.

The CMDh agreed with the PRAC's conclusions and endorsed the PRAC's recommendations on the use of flupirtine-containing medicines. The CMDh position was sent to the European Commission, which endorsed it and adopted a final legally binding decision valid throughout the EU on 5 September 2013.

Key facts

About this medicine
Approved name
Flupirtine-containing medicines
International non-proprietary name (INN) or common name
flupirtine
Class
-
About this procedure
Current status
European Commission final decision
Type
Article 107i procedures

This type of procedure is triggered when a Member State or the European Commission consider that urgent action is necessary because of a safety issue. Situations that fall under this procedure include consideration for suspension or revocation of the marketing authorisation for a medicine, the prohibition of supply of a medicine or major changes to the marketing authorisation such as deletion of indications, reduction of the recommended dose or new contraindications. The procedure is also applicable in case of a safety issue with a class of medicines.

Decision making model
PRAC-CMDh
Authorisation model
Nationally authorised product(s)
Key dates and outcomes
Procedure start date
07/03/2013
PRAC recommendation date
13/06/2013
CHMP opinion/CMDh position date
26/06/2013
EC decision date
05/09/2013
Outcome
Risk minimisation measures

Data submission

The Agency invites all stakeholders (e.g. healthcare professionals, patients' organisations and the general public) to submit data relevant to this procedure. This is in accordance with Article 107j(1) of Directive 2001/83/EC.

The following requirements apply for data to be considered:

  • Submissions must be accompanied by the submission form below, with all fields completed. The form must be used with Adobe Reader X+ or Adobe Acrobat X+:
    PDF iconStakeholder's submission form
  • The submission of all data should take place by 8 April 2013.

Submitting data

Send the completed form electronically to the stakeholders' submission inbox (public@ema.europa.eu). Specify the name of the medicine in the subject line of the e-mail.

The size of the submission file should not exceed 25 MB. If your attempt to send your data package to the dedicated e-mail address is unsuccessful, please use alternative submission means.

It is of the utmost importance that data are provided promptly, to avoid undermining the safety review. Due to the urgent nature of the procedure, you are strongly advised to submit your data in English.

Protection of personal data

Personal data submitted are subject to data-protection rules as established by Regulation (EC) 45/2001. They will be treated in accordance with the PDF iconspecific privacy statement for public consultations .

Treatment and publication of data

Data submitted will be received and recorded by the Agency.

The Agency will prepare a list of all submissions received, which will be published as an annex to the PRAC assessment report for transparency purposes and public awareness.

Please note that all data submitted in the context of this procedure may be shared and disclosed in the public domain.

All documents

Procedure started

  • List item

    Flupirtine-containing medicines Article-107i procedure - PRAC list of questions to be addressed by the stakeholders (PDF/59.21 KB)

    Adopted

    First published: 08/03/2013
    Last updated: 08/03/2013
    EMA/PRAC/144072/2013

  • List item

    Flupirtine-containing medicines Article-107i procedure - PRAC list of questions to be addressed by the marketing-authorisation holders (PDF/69.15 KB)

    Adopted

    First published: 08/03/2013
    Last updated: 08/03/2013
    EMA/PRAC/137417/2013

  • List item

    Flupirtine-containing medicines Article-107i procedure - Timetable for the procedure (PDF/75.32 KB)

    Adopted

    First published: 08/03/2013
    Last updated: 21/05/2013
    EMA/PRAC/137732/2013

  • List item

    Flupirtine-containing medicines Article-107i procedure - Notification (PDF/1.44 MB)

    Adopted

    First published: 08/03/2013
    Last updated: 08/03/2013

  • List item

    Flupirtine-containing medicines Article-107i procedure - Stakeholders' submission form (PDF/128.21 KB)

    Adopted

    First published: 08/03/2013
    Last updated: 08/03/2013
    EMA/639499/2012

  • List item

    Flupirtine-containing medicines Article-107i procedure - Review started (PDF/65.65 KB)

    Adopted

    First published: 08/03/2013
    Last updated: 08/03/2013
    EMA/139661/2013

  • List item

    Flupirtine-containing medicines Article-107i procedure - Annex I (PDF/125.61 KB)

    Adopted

    First published: 08/03/2013
    Last updated: 08/03/2013
    EMA/147828/2013

  • List item

    Flupirtine-containing medicines Article-107i procedure - Rationale for triggering (PDF/97.19 KB)

    Adopted

    First published: 08/03/2013
    Last updated: 08/03/2013

  • Recommendation provided by Pharmacovigilance Risk Assessment Committee

    Position provided by CMDh

  • List item

    Flupirtine-containing medicines Article-107i procedure - Annex I (PDF/110.55 KB)


    First published: 18/07/2013
    Last updated: 18/07/2013

  • List item

    Flupirtine-containing medicines Article-107i procedure - Annex IV (PDF/15.86 KB)


    First published: 18/07/2013
    Last updated: 18/07/2013

  • List item

    Flupirtine-containing medicines Article-107i procedure - Annex III (PDF/39.88 KB)


    First published: 18/07/2013
    Last updated: 18/07/2013

  • List item

    Flupirtine-containing medicines Article-107i procedure - Annex II (PDF/109.59 KB)


    First published: 18/07/2013
    Last updated: 18/07/2013

  • List item

    Flupirtine-containing medicines Article-107i procedure - Divergent positions to CMDh position (PDF/24.03 KB)


    First published: 18/07/2013
    Last updated: 18/07/2013

  • List item

    Flupirtine-containing medicines Article-107i procedure - Restrictions in the use of flupirtine-containing medicines - CMDh endorses PRAC recommendation (PDF/77.44 KB)


    First published: 28/06/2013
    Last updated: 28/06/2013
    EMA/384191/2013

  • European Commission final decision

  • List item

    Flupirtine-containing medicines Article-107i procedure - Restrictions in the use of flupirtine-containing medicines (PDF/88.15 KB)


    First published: 21/11/2013
    Last updated: 21/11/2013
    EMA/563900/2013

  • List item

    Flupirtine-containing medicines Article-107i procedure - Restrictions in the use of flupirtine-containing medicines (PDF/88.15 KB)


    First published: 21/11/2013
    Last updated: 21/11/2013
    EMA/563900/2013

  • 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

    How useful was this page?

    Add your rating