Substances related to nicotinic acid

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

Overview

Acipimox only to be used as additional or alternative treatment to reduce high triglyceride levels

CMDh endorses PRAC recommendation

On 18 December 2013, the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh)1 confirmed by majority that medicines containing acipimox should have their marketing authorisations amended to ensure that they are used across the European Union only as an additional or alternative treatment in type IIb and type IV hyperlipoproteinaemia. These are conditions involving hypertriglyceridaemia (high levels of triglycerides, a type of fat, in the blood), with or without increased cholesterol. Acipimox-containing medicines should be used when changes in lifestyle, including diet and exercise, and treatment with other medicines are not adequate.

These recommendations were originally made by the European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC) at its meeting of 5-8 November 2013. The original reason for the review of acipimox was HPS2-THRIVE, a large study which looked at the long-term effect of the combination of nicotinic acid (a substance related to acipimox) and another medicine, laropiprant, in treating lipid disorders. The study showed that adding this combination to treatment with statins (another class of medicines used to treat lipid disorders) did not lead to additional benefits in reducing the risk of major vascular events such as heart attack and stroke, but did result in a higher frequency of non-fatal but serious side effects. As a result, the European Medicines Agency recommended the suspension of medicines containing the combination of nicotinic acid and laropiprant across the EU2. Because acipimox was related to nicotinic acid and was marketed for lipid disorders in the EU, its benefit-risk balance was also then reviewed.

After looking at the available data on acipimox, including evidence from the literature, spontaneous reports of adverse effects and advice from a group of experts in the treatment of lipid disorders, as well as data from HPS2-THRIVE, the PRAC concluded that acipimox continues to have a role as an additional or alternative treatment to reduce triglycerides in those forms of hyperlipoproteinaemia that involve high triglyceride levels (with or without increased cholesterol), in patients in whom lifestyle changes and use of other medicines such as fibrates and statins are not adequate. The results from HPS2-THRIVE could not be applied directly to acipimox since the study investigated the effect of the combination with laropiprant, whose effects were not established, and possible differences between nicotinic acid and acipimox were also identified. However, findings from the HPS2-THRIVE study were used to expand the warnings in the acipimox product information concerning a possible increased risk of painful muscle damage when acipimox is used together with a statin.

The CMDh endorsed the PRAC recommendations by majority at its meeting of 16-18 December 2013 and its position was sent to the European Commission which endorsed it and issued an EU-wide legally binding decision on 20 February 2014.

Key facts

About this medicine
Approved name
Substances related to nicotinic acid
International non-proprietary name (INN) or common name
acipimox
Associated names
Olbetam
Class
Lipid-lowering agents
About this procedure
Current status
European Commission final decision
Reference number
EMEA/H/A-31/1366
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
07/03/2013
PRAC recommendation date
07/11/2013
CHMP opinion/CMDh position date
18/12/2013
EC decision date
20/02/2014
Outcome
Variation

All documents

Procedure started

Position provided by CMDh

European Commission final decision

  • List item

    Acipimox only to be used as additional or alternative treatment to reduce high triglyceride levels (PDF/83.76 KB)


    First published: 13/03/2014
    Last updated: 13/03/2014
    EMA/108603/2014

  • List item

    Substances related to nicotinic acid Article-31 referral - Annex I (PDF/37.26 KB)


    First published: 13/03/2014
    Last updated: 13/03/2014

  • List item

    Acipimox only to be used as additional or alternative treatment to reduce high triglyceride levels (PDF/83.76 KB)


    First published: 13/03/2014
    Last updated: 13/03/2014
    EMA/108603/2014

  • List item

    Substances related to nicotinic acid Article-31 referral - Annex II (PDF/43.15 KB)


    First published: 13/03/2014
    Last updated: 13/03/2014

  • List item

    Substances related to nicotinic acid Article-31 referral - Annex III (PDF/34.76 KB)


    First published: 13/03/2014
    Last updated: 13/03/2014

  • List item

    Substances related to nicotinic acid Article-31 referral - Assessment report (PDF/169.92 KB)

    Adopted

    First published: 13/03/2014
    Last updated: 13/03/2014
    EMA/PRAC/18751/2014

  • List item

    Substances related to nicotinic acid Article-31 referral - CMDh divergent position (PDF/21.36 KB)


    First published: 13/03/2014
    Last updated: 13/03/2014

  • 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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