Levothyroxine Alapis - referral

Current status

European Commission final decision

Overview

On 18 October 2012, 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 Levothyroxine Alapis. The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that the benefits of Levothyroxine Alapis do not outweigh its risks, and the marketing authorisation cannot be granted in the Netherlands or in the following EU Member States: Belgium, Bulgaria, Cyprus, Germany, Greece, Malta, Portugal, Romania and United Kingdom.

What is Levothyroxine Alapis?

Levothryoxine Alapis is a medicine that contains the active substance levothyroxine sodium. It was to be available as oral drops (100 microgram/ml). The active substance in Levothyroxine Alapis, levothyroxine sodium, is a synthetic form of the hormone thyroxine. Thyroxine is normally produced in the body by the thyroid gland in the neck. It controls many body functions, mainly to do with growth and energy. Levothyroxine Alapis was intended to be used to treat:

• conditions in which the thyroid gland is underactive (hypothyroidism, including diffuse non-toxic goitre) and so does not make enough thyroxine for the body's needs;
• a condition known as Hashimoto's thyroiditis, in which the immune system (the body's natural defences) attacks the thyroid causing it to swell and preventing it from working properly;
• thyroid cancer.

Why was Levothyroxine Alapis reviewed?

Alapis S.A. submitted an application for Levothyroxine Alapis to the Dutch medicines regulatory agency for a decentralised procedure. This is a procedure where one Member State (the 'reference Member State', in this instance the Netherlands) 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 Belgium, Bulgaria, Cyprus, Germany, Greece, Malta, Portugal, Romania and United Kingdom).

However, the Member States were not able to reach an agreement and the Dutch agency referred the matter to the CHMP for arbitration on 26 January 2012.

The grounds for the referral were concerns raised by the UK related to the dropper insert as a proposed administration device, due to the large number of drops that may be required and concerns about its accuracy in delivering the required dose. This could potentially lead to medication errors and pose a risk to public health. In addition there were concerns over the safety of the combined long-term use of the ingredients ethanol and propylene glycol at the proposed concentrations, particularly in children.

What are the conclusions of the CHMP?

Based on evaluation of the currently available data and the scientific discussion within the Committee, the CHMP agreed that there was a risk that the dropper used for delivery might deliver variable doses, and that large numbers of drops might be hard to count. Since the solution is highly concentrated and the active substance highly potent, there was an unacceptable risk of serious medication errors. In addition, there remained concern over the safety of the long-term use of the ingredients ethanol and propylene glycol in children, and some groups of adults such as those with alcoholism. Therefore the CHMP concluded that the benefits of Levothyroxine Alapis do not outweigh its risks, and that the marketing authorisation should not be granted in the concerned Member States.

The European Commission issued a decision on 14 January 2013.

Questions and answers on Levothyroxine Alapis and associated names (levothyroxine sodium, oral drops, 100 microgram/ml)

Reference Number: EMA/659681/2012 Rev.1

Key facts

About this medicine

• Approved name:
  Levothyroxine Alapis
• International non-proprietary name (INN) or common name:
  levothyroxine sodium
• Class:
  -

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-29/1328
• 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:
  18/10/2012
• EC decision date:
  14/01/2013

All documents

Opinion provided by Committee for Medicinal Products for human Use

Questions and answers on Levothyroxine Alapis and associated names (levothyroxine sodium, oral drops, 100 microgram/ml)

Reference Number: EMA/659681/2012 Rev.1

European Commission final decision

Levothyroxine Alapis- Article 29 referral - Assessment report

Adopted Reference Number: EMA/701628/2012

Levothyroxine Alapis - Article 29(4) referral - Annex I

Levothyroxine Alapis - Article 29(4) 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.