Ethirfin - referral

Current status

European Commission final decision

Overview

The European Medicines Agency has completed an arbitration procedure for Ethirfin and associated names. The Agency's Committee for Medicinal Products for Human Use (CHMP) had been asked to arbitrate on the renewal of the marketing authorisation for Ethirfin. The Committee concluded that the marketing authorisation should not be renewed, as patients taking Ethirfin and alcohol are at risk of developing serious side effects.

The European Commission issued a decision on this opinion on 20 December 2010.

What is Ethirfin?

Ethirfin is a medicine that contains the active substance morphine sulphate. It is used to treat severe pain. Ethirfin is available as 'prolonged-release' capsules that release the active substance slowly. They are taken once a day.

Why was Ethirfin reviewed?

Ethirfin was authorised in the European Union (EU) under a mutual recognition procedure on the basis of the initial authorisation granted by Denmark on 15 July 2005. The company applied for the marketing authorisation to be renewed in Denmark (the 'reference Member State'). This renewal was to be recognised in Germany, Ireland, Italy and the United Kingdom (the 'concerned Member States'). Because these Member States were not able to reach an agreement, the German and United Kingdom medicines regulatory agencies referred the matter to the CHMP for arbitration on 30 October 2009.

The grounds for the referral were concerns that the active substance in the capsules could be released too quickly if the capsules are taken with alcohol, because they contain a 'polymethacrylate-triethylcitrate' coating to control the release of morphine and this coating is soluble in alcohol. The rapid release of the active substance is called 'dose dumping' and could put patients at risk of exposure to large doses of morphine, leading to side effects such as respiratory depression (an inhibition of breathing).

What are the conclusions of the CHMP?

Based on evaluation of the currently available data and the scientific discussion within the Committee, the CHMP concluded that there is a significant interaction between Ethirfin and alcohol, and that patients taking Ethirfin and alcohol are at risk of developing serious side effects. Therefore the benefits of Ethirfin do not outweigh its risks, and the marketing authorisation for Ethirfin should not be renewed in all concerned Member States.

Questions and answers on Ethirfin and associated names (morphine sulphate, prolonged-release capsules, 20, 60, 120 and 200 mg)

Adopted Reference Number: EMA/468843/2010

Key facts

About this medicine

• Approved name:
  Ethirfin
• International non-proprietary name (INN) or common name:
  morphine sulphate

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-29/001248
• 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:
  23/09/2010
• EC decision date:
  20/12/2010

All documents

Ethirfin - Article 29 referral - Annex II

Adopted

Questions and answers on Ethirfin and associated names (morphine sulphate, prolonged-release capsules, 20, 60, 120 and 200 mg)

Adopted Reference Number: EMA/468843/2010

European Commission final decision

Ethirfin - Article 29 referral - Annex I

Adopted

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.