SGLT2 inhibitors (previously canagliflozin)

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CHMP opinion
  • European Commission final decision
Current status:
European Commission final decision

Overview


SGLT2 inhibitors: information on potential risk of toe amputation to be included in prescribing information

Diabetes patients reminded of importance of preventative foot care

On 24 February 2017, the European Medicines Agency (EMA) informed about a potential increased risk of lower limb amputation (mostly affecting the toes) in patients taking the SGLT2 inhibitors canagliflozin, dapagliflozin and empagliflozin used for type 2 diabetes.

Patients taking these medicines are reminded to check their feet regularly and follow their doctor's advice on routine preventative foot care. They should also tell their doctor if they notice any wounds or discoloration, or if their feet are tender or painful.
The review of SGLT2 inhibitors was prompted by an increase in lower limb amputations (mostly affecting the toes) in patients taking canagliflozin in two clinical trials, CANVAS and CANVAS-R. The studies involved patients at high risk of heart problems and compared canagliflozin with placebo (a dummy treatment).

All patients with diabetes (especially those with poorly controlled diabetes and problems with the heart and blood vessels) are at higher risk of infection and ulcers (sores) which can lead to amputations. The mechanism by which canagliflozin may increase the risk of amputation is still unclear.

An increase in lower limb amputations has not been seen in studies with other medicines in the same class, dapagliflozin and empagliflozin. However, data available to date are limited and the risk may also apply to these other medicines.
Further data are expected from ongoing studies with canagliflozin, dapagliflozin and empagliflozin.

A warning of the potential increased risk of toe amputation has been included in the prescribing information for these medicines. For canagliflozin, the prescribing information also lists lower limb amputation as an uncommon side effect (occurring in between 1 and 10 patients in 1,000). Doctors may consider stopping treatment with canagliflozin if patients develop significant foot complications such as infection or skin ulcers.

The review of SGLT2 inhibitors was carried out by EMA's Pharmacovigilance Risk Assessment Committee (PRAC). The PRAC recommendations were endorsed by the Committee for Medicinal Products for Human Use (CHMP) and sent to the European Commission, which issued a final legally-binding decision valid throughout the EU.

Key facts

About this medicine
Approved name
SGLT2 inhibitors (previously canagliflozin)
International non-proprietary name (INN) or common name
  • canagliflozin
  • empagliflozin
  • dapagliflozin
  • metformin
Associated names
  • Xigduo
  • Ebymect
  • Edistride
  • Synjardy
  • Forxiga
  • Jardiance
  • Vokanamet
  • Invokana
About this procedure
Current status
European Commission final decision
Reference number
EMEA/H/A-20/1442
Type
Article 20 procedures

This type of procedure is triggered for medicines that have been authorised via the centralised procedure in case of quality, safety or efficacy issues.

Decision making model
PRAC-CHMP-EC
Authorisation model
Centrally authorised product(s)
Key dates and outcomes
Procedure start date
15/04/2016
PRAC recommendation date
09/02/2017
CHMP opinion/CMDh position date
23/02/2017
EC decision date
04/05/2017
Outcome
Risk minimisation measures

All documents

Procedure started

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Opinion provided by Committee for Medicinal Products for Human Use

European Commission final decision

  • List item

    SGLT2 inhibitors (previously canagliflozin) Article-20 procedure - Annex I-III - Forxiga (PDF/275.72 KB)


    First published: 08/05/2017
    Last updated: 08/05/2017

  • List item

    SGLT2 inhibitors (previously canagliflozin) Article-20 procedure - Annex I-III - Edistride (PDF/275.87 KB)


    First published: 08/05/2017
    Last updated: 08/05/2017

  • List item

    SGLT2 inhibitors (previously canagliflozin) Article-20 procedure - PRAC assessment report (PDF/254.07 KB)

    Adopted

    First published: 08/05/2017
    Last updated: 08/05/2017
    EMA/PRAC/637349/2016

  • List item

    SGLT2 inhibitors (previously canagliflozin) Article-20 procedure - Annex I-III - Synjardy (PDF/440.59 KB)


    First published: 08/05/2017
    Last updated: 08/05/2017

  • List item

    SGLT2 inhibitors (previously canagliflozin) Article-20 procedure - Annex I-III - Vokanamet (PDF/388.29 KB)


    First published: 08/05/2017
    Last updated: 08/05/2017

  • List item

    SGLT2 inhibitors (previously canagliflozin) Article-20 procedure - Annex I-III - Jardiance (PDF/370.91 KB)


    First published: 08/05/2017
    Last updated: 08/05/2017

  • List item

    SGLT2 inhibitors (previously canagliflozin) Article-20 procedure - Annex I-III - Invokana (PDF/321.75 KB)


    First published: 08/05/2017
    Last updated: 08/05/2017

  • List item

    SGLT2 inhibitors (previously canagliflozin) Article-20 procedure - SGLT2 inhibitors: information on potential risk of toe amputation to be included in prescribing information (April 2017) (PDF/83.85 KB)


    First published: 08/05/2017
    Last updated: 08/05/2017
    EMA/118223/2017

  • List item

    SGLT2 inhibitors (previously canagliflozin) Article-20 procedure - Annex I-III - Ebymect (PDF/329.44 KB)


    First published: 08/05/2017
    Last updated: 08/05/2017

  • List item

    SGLT2 inhibitors (previously canagliflozin) Article-20 procedure - Annex I-III - Xigduo (PDF/327.51 KB)


    First published: 08/05/2017
    Last updated: 08/05/2017

  • List item

    SGLT2 inhibitors (previously canagliflozin) Article-20 procedure - Annex IV (PDF/41.36 KB)


    First published: 08/05/2017
    Last updated: 08/05/2017

  • Description of documents published

    Please note that some of the listed documents apply only to certain procedures.

    • Overview - lay-language summary of the stage of the procedure
    • Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
    • Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
    • List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
    • Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
    • List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
    • List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
    • Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
    • Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
    • Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
    • Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
    • Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
    • Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
    • Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
    • Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)

    Note that older documents may have different titles.

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