Saroten and associated names - referral

Current status

European Commission final decision

Overview

Outcome of a procedure under Article 30 of Directive 2001/83/EC

On 23 February 2017, the European Medicines Agency completed a review of Saroten. The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that there is a need to harmonise the prescribing information for amitriptyline in the European Union (EU).

What is Saroten?

Saroten is a medicine used to treat a variety of conditions in the EU, including depression and various depressive states, a number of disorders associated with chronic (long-term) pain including the prevention of migraine or recurring headaches, and for the treatment of nocturnal enuresis (bedwetting) in children. Saroten is available as modified-release capsules, tablets (including modified-release tablets), and as a solution for injection. It contains the active substance amitriptyline.

Saroten and associated names (such as Redomex and Sarotex) is marketed in Austria, Belgium, Cyprus, Denmark, Estonia, Germany, Greece, Luxembourg, the Netherlands and Sweden, and also in Norway. The companies that market these medicines include Bayer GmbH and Lundbeck A/S. Amitriptyline is also available in EU countries as generic amitriptyline.

Why was Saroten reviewed?

Saroten is authorised in the EU via national procedures. This has led to divergences across Member States in the way the medicine can be used, as seen in the differences in the summaries of product characteristics (SmPCs), labelling and package leaflets in the countries where the medicine is marketed.

On 17 December 2015, the Greek medicines regulator, the National Organization for Medicines (EOF), referred the matter to the CHMP in order to harmonise the marketing authorisations for Saroten and associated names in the EU.

What are the conclusions of the CHMP?

The CHMP, in the light of the data submitted and the scientific discussion within the Committee, was of the opinion that the SmPCs, labelling and package leaflets should be harmonised across the EU.

The areas harmonised include:

4.1 Therapeutic indications

The CHMP agreed that Saroten and associated names could be used in adults for:

• the treatment of serious depression (major depressive disorder)
• the treatment of neuropathic pain (long-lasting pain caused by nerve damage)
• treatment to prevent chronic tension-type headache (CTTH)
• treatment to prevent migraine.

While harmonising the use of Saroten in neuropathic pain and prevention of CTTH and migraine, the CHMP considered that Saroten should not be used for other forms of chronic pain.

The Committee agreed that the medicine could also be used in children from 6 years of age to treat nocturnal enuresis. It should only be prescribed by a specialist doctor and should only be used when physical causes of the problem (including conditions such as spina bifida) have been ruled out and when other treatments, including other medicines used for this problem, have not worked.

4.2 Posology and method of administration

The CHMP harmonised the doses to be used in the approved indications. Treatment is usually by mouth and the dose depends on the condition to be treated; as the strengths of the different tablets and capsules can vary, it is important to choose one that allows the right dose to be given. Treatment for depression or chronic pain may take 2 to 4 weeks to start to work, and treatment for depression should be continued for up to 6 months after the patient gets better. For initial treatment in hospital patients, Saroten can also be given as an injection into a muscle or a drip (infusion) into a vein.

The medicine should not be given to children to treat depression or pain. For the treatment of bedwetting the dose is given an hour to an hour-and-a-half before bedtime and a course of treatment should last for a maximum of 3 months.

4.3 Contra-indications

Saroten must not be used in patients who are hypersensitive (allergic) to the medicine or any of its ingredients. It must also not be used in patients who have recently had a heart attack or have disorders of the electrical activity or rhythm of the heart or reduced blood flow to the heart muscle, nor in those with severe liver disease. Use is not permitted in children less than 6 years of age.

Patients must not receive treatment with certain other medicines called monoamine oxidase inhibitors (MAOIs) at the same time as Saroten, and there should be a gap (usually of two weeks) between stopping one of these medicines and starting Saroten, or vice versa.

Other changes

The CHMP harmonised other sections of the SmPC including the warnings and precautions relating to treatment (4.4), and recommendations not to use the medicine during pregnancy and to consider the risks and benefits of use during breast feeding (4.6). Other amendments included the information on interactions with other medicines (4.5), and the list of side effects (4.8).

The European Commission issued a decision on this opinion on 08/05/2017.

Questions and answers on Saroten and associated names (amitriptyline)

Reference Number: EMA/118128/2017 Rev.1

Key facts

About this medicine

• Approved name:
  Saroten and associated names
• International non-proprietary name (INN) or common name:
  amitriptyline
• Associated names:
  • Saroten Retard
  • Redomex
  • Redomex Diffucaps
  • Saroten Tabs
  • Saroten retard Tabs
  • Saroten 2ml
  • Sarotex
  • Sarotex Retard
  • Sarotex Retard 25
  • Sarotex Retard 50
• Class:
  antidepressant

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-30/1430
• Type:
  Article 30 referrals

  This type of referral is triggered when Member States have adopted different decisions over the years for some medicines (e.g. different indications, contraindications or posology) and there is a need to harmonise across the EU.

Key dates and outcomes

• CHMP opinion date:
  23/02/2017
• EC decision date:
  08/05/2017

All documents

Opinion provided by Committee for Medicinal Products for human Use

Questions and answers on Saroten and associated names (amitriptyline)

Reference Number: EMA/118128/2017 Rev.1

European Commission final decision

Saroten Article-30 referral - Assessment report

AdoptedReference Number: EMA/255467/2017

Saroten Article-30 referral - Annex I

Saroten Article-30 referral - Annex II

Saroten Article-30 referral - Annex III

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.