Xofigo

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Summary

 

Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone

Ongoing clinical study shows increased risk of death and fractures with the combination

On 8 March 2018, the European Medicines Agency (EMA) recommended contraindicating the use of the prostate cancer medicine Xofigo (radium-223 dichloride) with Zytiga (abiraterone acetate) and prednisone/prednisolone, due to an increased risk of death and fractures with this combination.

EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) had reviewed the preliminary data from an ongoing clinical study in metastatic prostate cancer patients. In this study 34.7% of patients treated with Xofigo, Zytiga and prednisone/prednisolone have died so far, compared with 28.2% of patients given placebo, Zytiga and prednisone/prednisolone.

Fractures have also occurred more frequently with the Xofigo combination than the placebo combination (26% versus 8.1%).

In view of the seriousness of the events reported, the PRAC took action by introducing a contraindication as a temporary measure to protect patients’ safety while an in-depth review of the benefits and risks of Xofigo is ongoing.

Xofigo is currently authorised for use in men whose prostate cancer has spread to the bones and is causing symptoms. The ongoing clinical study includes metastatic prostate cancer patients who have not previously received chemotherapy and who have no symptoms or only mild symptoms, such as pain. Patients have completed the Xofigo part of the study, and the combination is no longer being used; all the patients involved are being monitored closely.

Healthcare professionals in the EU must not use a combination of Xofigo with the anti-androgen Zytiga and prednisone/prednisolone, and should stop this combination in men currently treated with it and review the treatment for these patients. Healthcare professionals are also warned that the safety and efficacy of Xofigo in combination with a class of medicines called second generation androgen receptor antagonists, such as Xtandi (enzalutamide), have not been established.

These are temporary measures until the ongoing in-depth review of the benefits and risks of Xofigo is complete. EMA will communicate further at the conclusion of the review.

Information for patients
  • Doctors are being advised that the medicine for prostate cancer Xofigo must not be used with the prostate cancer medicine Zytiga and prednisone/prednisolone because there is evidence that the combination may be harmful to patients due to a possible increased risk of fractures and death.
  • If you are being treated with this combination, your doctor will alter your treatment.
  • Xofigo and Zytiga can continue to be used separately, in line with the recommendations in their product information.
  • If you are being treated with Xofigo and have any questions, you should contact your doctor.
Information for healthcare professionals
  • Xofigo must not be used with the anti-androgen Zytiga (abiraterone acetate) and prednisone/prednisolone because of possible increased risk of fractures and mortality.
  • The safety and efficacy of Xofigo in combination with second generation androgen receptor antagonists such as Xtandi (enzalutamide) have not been established.
  • Xofigo and Zytiga can continue to be used separately, in line with the recommendations in their product information.
  • Further information will be made available once an ongoing review of the evidence is complete.
More about the medicine

Xofigo is used to treat men with cancer of the prostate (a gland of the male reproductive system). It is authorised for use when medical or surgical castration (stopping the production of male hormones in the body using medicines or surgery) does not work, and when the cancer has spread to the bones and is causing symptoms such as pain but is not known to have spread to other internal organs.

The ongoing study of Xofigo in combination with Zytiga and prednisone/prednisolone included patients with castration-resistant prostate cancer that has spread mainly to the bones, who have no symptoms or only mild symptoms and who have not been treated with chemotherapy.

Xofigo was authorised in the European Union in November 2013. More information on Xofigo is available.

More about the procedure

The review of Xofigo has been initiated at the request of the European Commission, under Article 20 of Regulation (EC) No 726/2004.

The review is being carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the Committee responsible for the evaluation of safety issues for human medicines, which will make a set of recommendations.

During the review, the PRAC made provisional recommendations to protect public health. This was sent to the European Commission (EC), which issued a provisional legally binding decision on 19 March 2018.

Once the PRAC review is concluded, its recommendations will be forwarded to the Committee for Medicinal Products for Human Use (CHMP), responsible for evaluating medicines for human use, which will adopt a final opinion.

The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all EU Member States.

Name Language First published Last updated
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone BG = bălgarski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone ES = español 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone CS = čeština 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone DA = dansk 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone DE = Deutsch 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone ET = eesti keel 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone EL = elliniká 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone EN = English 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone FR = français 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone IT = italiano 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone LV = latviešu valoda 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone LT = lietuvių kalba 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HU = magyar 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone MT = Malti 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone NL = Nederlands 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone PL = polski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone PT = português 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone RO = română 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone SK = slovenčina 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone SL = slovenščina 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone FI = suomi 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone SV = svenska 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09

Key facts

About this medicine

Approved nameXofigo
International non-proprietary name (INN) or common name

radium Ra223 dichloride

Associated names
Class

About this procedure

Current statusUnder evaluation
Reference numberEMEA/H/A-20/1459/C/002653/0028
TypeArticle 20 procedures

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

Decision making modelPRAC-CHMP-EC
Authorisation modelCentrally authorised product(s)

Key dates and outcomes

Procedure start date30/11/2017
PRAC recommendation date08/03/2018
OutcomeRisk minimisation measures

All documents

Procedure started

Name Language First published Last updated
Xofigo Article-20 procedure - Review started HR = Hrvatski 2017-12-01  
Xofigo Article-20 procedure - Timetable for the procedure HR = Hrvatski 2017-12-01 2018-03-09
Xofigo Article-20 procedure - PRAC list of questions HR = Hrvatski 2017-12-01  
Xofigo Article-20 procedure - Notification HR = Hrvatski 2017-12-01  

Under evaluation

Name Language First published Last updated
Xofigo Article-20 procedure - Assessment report on provisional measures HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Annex I-II-III HR = Hrvatski 2018-03-09  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Scientific conclusions HR = Hrvatski 2018-03-21  
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09
Xofigo Article-20 procedure - Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone HR = Hrvatski 2018-03-09 2018-04-09

Document description:

  • Annex I - List of the medicines affected by the referral
  • Annex II - Scientific conclusions of the Committee for Medicinal Products for Human Use (CHMP) or Coordination Group for Mutual Recognition and Decentralised Procedures - Human (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 / CMDh assessment report - The assessment and conclusions of the PRAC and CHMP or CMDh on the issues investigated

Current status:
Under evaluation