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



EMA restricts use of prostate cancer medicine Xofigo

Medicine to be used only after two previous treatments or when other treatments cannot be taken

On 26 July 2018, the European Medicines Agency concluded its review of the cancer medicine Xofigo (radium-223 dichloride), and recommended restricting its use to patients who have had two previous treatments for metastatic prostate cancer (prostate cancer that has spread to the bone) or who cannot receive other treatments.

Xofigo must also not be used with the medicines Zytiga (abiraterone acetate) and the corticosteroid prednisone or prednisolone. Xofigo should not be used with other systemic cancer therapies, except for treatments to maintain reduced levels of male hormones (hormone therapy). The medicine should also not be used in patients who have no symptoms, in line with the current indication; in addition, the use of Xofigo is not recommended in patients with a low number of bone metastases called osteoblastic bone metastases.

The review of Xofigo was carried out by EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) after data from a clinical study suggested that patients given Xofigo in combination with Zytiga and prednisone/prednisolone could be at risk of dying earlier and had more fractures than patients given placebo (a dummy treatment) with Zytiga and prednisone/prednisolone. The study included patients with no or only mild symptoms, whereas Xofigo is only authorised in patients with symptoms. In addition, the combination used in this study is now contraindicated. In the study, patients given the combination with Xofigo died on average 2.6 months earlier than those given the combination with placebo. In addition, 29% of patients who received the Xofigo combination had fractures, compared with 11% of patients given the placebo combination.

It is thought that Xofigo, which is taken up by the bone, accumulates at sites where the bone is already damaged, for example by osteoporosis or micro-fractures, increasing the risk of fracture. However, the reasons for a possible earlier death seen in this study are not fully understood. The company that markets Xofigo will have to conduct studies to further characterise these events and clarify the mechanisms behind them.

The PRAC’s recommendations were endorsed by EMA’s Committee for Medicinal Products for Human Use (CHMP). The European Commission issued a final legal decision valid throughout the EU on 28 September 2018.


Key facts

About this medicine
Approved name
International non-proprietary name (INN) or common name
radium Ra223 dichloride
Associated names
About this procedure
Current status
European Commission final decision
Reference number
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.

Authorisation model
Centrally authorised product(s)
Decision making model
Key dates and outcomes
Procedure start date
PRAC recommendation date
CHMP opinion/CMDh position date
EC decision date
Risk minimisation measures

All documents

Procedure started

Under evaluation

  • List item

    Xofigo Article-20 procedure - Assessment report on provisional measures (PDF/916.85 KB)

    First published: 21/03/2018
    Last updated: 21/03/2018

  • List item

    Xofigo Article-20 procedure - Scientific conclusions (PDF/39.47 KB)

    First published: 21/03/2018
    Last updated: 21/03/2018

  • List item

    Xofigo Article-20 procedure - Annex I-II-III (PDF/535.61 KB)

    First published: 09/03/2018
    Last updated: 09/03/2018

  • List item

    Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone (PDF/96.06 KB)

    First published: 09/03/2018
    Last updated: 09/04/2018

  • Recommendation provided by Pharmacovigilance Risk Assessment Committee

    Opinion provided by Committee for Medicinal Products for Human Use

    European Commission final decision

  • List item

    Xofigo Article-20 procedure - EMA restricts use of prostate cancer medicine Xofigo (PDF/93.99 KB)

    First published: 11/10/2018

  • List item

    Xofigo Article-20 procedure - Annex IV (PDF/77.6 KB)

    First published: 11/10/2018

  • List item

    Xofigo Article-20 procedure - Annex I, II, III

    First published: 11/10/2018

  • List item

    Xofigo Article-20 procedure - Assessment report (PDF/1.62 MB)

    First published: 11/10/2018

  • 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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