Diclofenac epolamine 50 mg tablets - referral

Current status

European Commission final decision

Overview

On 21 July 2016, the European Medicines Agency completed an arbitration procedure following a disagreement among Member States of the European Union (EU) regarding the authorisation of the medicine diclofenac epolamine (50 mg tablets). The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that the benefits of this product do not outweigh its risks, and the marketing authorisation cannot be granted in the United Kingdom (UK) or in the following Member States of the EU: Czech Republic, France and Slovakia.

What is diclofenac epolamine (50 mg tablets)?

The active substance in this medicine, diclofenac, is used for relief of pain and inflammation. Diclofenac is a 'non-steroidal anti-inflammatory drug' (NSAID) which reduces the body's production of substances called prostaglandins. Since some prostaglandins are involved in causing pain and inflammation at sites of injury or damage in the body, reduced prostaglandin production reduces pain and inflammation.

Diclofenac epolamine (50 mg tablets) is a generic medicine based on a 'reference medicine', Flector, which is authorised in France. The medicine was to be marketed as Diclofenac.

Why is diclofenac epolamine (50 mg tablets) reviewed?

Altergon Italia srl submitted diclofenac epolamine (50 mg tablets) to the UK medicines regulatory agency for a decentralised procedure. This is a procedure where one Member State (the 'reference Member State', in this instance the UK) assesses a medicine with a view to granting a marketing authorisation that will be valid in this country as well as in other Member States (the 'concerned Member States', in this instance Czech Republic, France and Slovakia).

However, the Member States were not able to reach an agreement and the UK medicines regulatory agency referred the matter to the CHMP for arbitration on 5 February 2016.

Because diclofenac epolamine (50 mg tablets) is a generic medicine, a study has been carried out to show that it is bioequivalent to the reference medicine, Flector, which is available as diclofenac epolamine granules to make a solution for drinking. Two medicines are bioequivalent when they produce the same levels of the active substance in the body.

The grounds for the referral were that the study performed had only shown the medicine was bioequivalent to the reference medicine when taken on an empty stomach. The French and Slovakian medicines regulatory agencies considered that a bioequivalence study of the medicine taken with food was also required because it is recommended to be preferably taken with food.

What are the conclusions of the CHMP?

Based on the evaluation of currently available data and the scientific discussion within the Committee, the CHMP concluded that bioequivalence to the reference medicine when taken with food has not been shown. A review of scientific literature showed variable reductions in the uptake of different forms of diclofenac when taken with food. The CHMP therefore considered that the study of the medicine taken on an empty stomach only was not sufficient to show that this product is as effective as the reference medicine. This is because it is recommended that this product is preferably taken with food, and food can have a big effect on the way the medicine is taken up into the body. The CHMP concluded that the benefits of these diclofenac epolamine 50 mg tablets do not outweigh their risks and recommended that marketing authorisation should not be granted in the UK or in the concerned Member States.

The European Commission issued a decision on this opinion on 22 September 2016.

Diclofenac Article-29 referral - Questions and answers on Diclofenac epolamine 50 mg tablets

Reference Number: EMA/490203/2016

Key facts

About this medicine

• Approved name:
  Diclofenac epolamine 50 mg tablets
• International non-proprietary name (INN) or common name:
  diclofenac

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-29/1434
• Type:
  Article 29(4) referrals

  This type of referral is triggered when there is a disagreement between Member States regarding a marketing authorisation application being evaluated in a mutual-recognition or decentralised procedure, on the grounds of a potential serious risk to public health.

Key dates and outcomes

• CHMP opinion date:
  25/02/2016
• EC decision date:
  22/09/2016

All documents

Opinion provided by Committee for Medicinal Products for human Use

Diclofenac Article-29 referral - Questions and answers on Diclofenac epolamine 50 mg tablets

Reference Number: EMA/490203/2016

European Commission final decision

Diclofenac Article-29 referral - Assessment report

Adopted Reference Number: EMA/629122/2016

Diclofenac Article-29 referral - Annex I

Diclofenac Article-29 referral - Annex II

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.