Testosterone-containing medicines

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

Overview

No consistent evidence of an increased risk of heart problems with testosterone medicines

The Coordination Group for Mutual Recognition and Decentralised Procedures - Human (CMDh), a regulatory body representing EU Member States, has agreed by consensus that there is no consistent evidence of an increased risk of heart problems with testosterone medicines in men who lack the hormone (a condition known as hypogonadism). However, the product information is to be updated in line with the most current available evidence on safety, and with warnings that the lack of testosterone should be confirmed by signs and symptoms and laboratory tests before treating men with these medicines.

The CMDh position follows a review by the EMA's Pharmacovigilance Risk Assessment Committee (PRAC) which looked at the risk of serious problems affecting the heart and circulation, particularly heart attacks, in men treated with these medicines. The review was started because of some recent studies suggesting an increase in heart problems in men using testosterone, compared with men not using it. The PRAC considered these studies along with available data from other studies and analyses, and information on safety collected since marketing, and found that the evidence regarding the risk of heart problems was inconsistent: some studies suggested increased risk, while others did not, and some of the studies had problems with the design that limited the conclusions that could be drawn from them. The PRAC also noted that the lack of testosterone itself could increase the risk of heart problems.

The PRAC recommended updating the product information in line with the latest evidence and to provide warnings about those who might be at increased risk of heart problems. The product information should make it clear that testosterone should only be used when an abnormally low level of the hormone has been confirmed by signs and symptoms and appropriate laboratory tests. Testosterone levels naturally fall somewhat with age, but restoration of these levels in healthy older men is not an authorised use of the medicine in the EU. The PRAC further considered that the risks of effects on the heart and circulation, and any potential mechanisms for such effects should continue to be monitored, and information from ongoing studies should be provided as part of the next regular safety review (to which these medicines, like all medicines in the EU, are subject).

The CMDh has endorsed the PRAC recommendations by consensus and they will now be directly implemented according to an agreed timetable by the Member States where the medicines are authorised.

Key facts

About this medicine
Approved name
Testosterone-containing medicines
International non-proprietary name (INN) or common name
testosterone
About this procedure
Current status
Position provided by CMDh
Reference number
EMEA/H/A-31/1396
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
10/04/2014
PRAC recommendation date
09/10/2014
CHMP opinion/CMDh position date
19/11/2014
Outcome
Variation

All documents

Procedure started

  • List item

    Testosterone Article-31 referral - Notification (PDF/169.05 KB)


    First published: 11/04/2014
    Last updated: 11/04/2014

  • List item

    Testosterone Article-31 referral - Timetable for the procedure (PDF/77.13 KB)


    First published: 11/04/2014
    Last updated: 11/07/2014
    EMA/PRAC/178709/2014

  • List item

    Testosterone Article-31 referral - PRAC list of questions (PDF/69.29 KB)


    First published: 11/04/2014
    Last updated: 11/04/2014
    EMA/PRAC/178703/2014

  • List item

    Testosterone Article-31 referral - Annex I (PDF/500.57 KB)


    First published: 11/04/2014
    Last updated: 08/01/2015

  • List item

    Testosterone Article-31 referral - Review started (PDF/73.59 KB)


    First published: 11/04/2014
    Last updated: 11/04/2014
    EMA/209962/2014

  • Recommendation provided by Pharmacovigilance Risk Assessment Committee

    Position provided by CMDh

  • List item

    Testosterone Article-31 referral - No consistent evidence of an increased risk of heart problems with testosterone medicines (PDF/95.59 KB)


    First published: 21/11/2014
    Last updated: 08/01/2015
    EMA/706140/2014

  • List item

    Testosterone Article-31 referral - Annex V (PDF/29.12 KB)


    First published: 08/01/2015
    Last updated: 08/01/2015
    EMEA/H/A-31/1396

  • List item

    Testosterone Article-31 referral - Annex IV (PDF/38.47 KB)


    First published: 08/01/2015
    Last updated: 08/01/2015
    EMEA/H/A-31/1396

  • List item

    Testosterone Article-31 referral - Annex II (PDF/57.68 KB)


    First published: 08/01/2015
    Last updated: 08/01/2015
    EMEA/H/A-31/1396

  • List item

    Testosterone Article-31 referral - PRAC assessment report (PDF/210.79 KB)


    First published: 05/12/2014
    Last updated: 05/12/2014
    EMA/CHMP/717942/2014

  • List item

    Testosterone Article-31 referral - Annex III (PDF/36.69 KB)


    First published: 21/11/2014
    Last updated: 08/01/2015

  • List item

    Testosterone Article-31 referral - No consistent evidence of an increased risk of heart problems with testosterone medicines (PDF/95.59 KB)


    First published: 21/11/2014
    Last updated: 08/01/2015
    EMA/706140/2014

  • 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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