Topamax - referral

Current status

European Commission final decision

Overview

The European Medicines Agency has completed a review of Topamax and associated names. The Agency's Committee for Medicinal Products for Human Use (CHMP) has concluded that there is a need to harmonise the prescribing information for Topamax and associated names in the European Union (EU) and the European Economic Area (EEA).
The review was carried out under an 'Article 30' referral¹.

The European Commission issued a decision on 1 October 2009.

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¹ Article 30 of Directive 2001/83/EC as amended, referral on the grounds of divergent decisions adopted by Member States

What is Topamax?

Topamax is an antiepileptic medicine. It is used as monotherapy (on its own) or as adjunctive therapy (together with other medicines) to prevent seizures (epileptic fits). Topamax is also used to prevent migraine headaches.

The exact way in which topiramate, the active substance in Topamax, works is unknown but it is thought to act by interfering with the activity of receptors on nerve cells, which leads to a reduction in electrical transmission. Because these cells are involved in causing seizures and in migraines, reducing their electrical activity helps to reduce the chance of having a seizure or developing a migraine.
Topamax is also available in the EU under other trade names: Topimax, Epitomax, Topiramat-Cilag, Topiramat-Janssen, Topamax Migräne and Topamac. It is available as tablets (25 mg, 50 mg, 100 mg and 200 mg) and capsules (15 mg, 25 mg and 50 mg).

The company that markets Topamax is Johnson & Johnson Pharma R & D.

Why was Topamax reviewed?

Topamax and associated names have been 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 (SPCs), labelling and package leaflets in the different countries where the product is marketed. Topamax has been identified as needing harmonisation by the Co-ordination Group on the Mutual Recognition and Decentralised Procedures – Human (CMD(h)). On 8 May 2008, the European Commission referred the matter to the CHMP in order to harmonise the marketing authorisations for Topamax and associated names in the EU and the EEA.

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 SPCs, labelling and package leaflets should be harmonised across the EU.

The areas harmonised include:

4.1 Therapeutic indications
The CHMP agreed on a harmonised wording for the indications:

• 'monotherapy in adults, adolescents and children over six years of age with partial seizures with or without secondary generalised seizures, and primary generalised tonic-clonic seizures;
• adjunctive therapy in children aged 2 years and above, adolescents and adults for partial onset seizures with or without secondary generalization or primary generalized tonic-clonic seizures and for the treatment of seizures associated with Lennox-Gastaut syndrome;
• in adults for the prophylaxis of migraine headache after careful evaluation of possible alternative treatment options. Topiramate is not intended for acute treatment.'

The CHMP had considered all available evidence and the various indications already authorised in different Member States. The main differences concerned the age of children that can be given Topamax, and the medicine's use in monotherapy and conversion to monotherapy. The CHMP removed a restriction that was present in some Member States that Topamax monotherapy be used for only newly diagnosed epilepsy.

4.2 Posology and method of administration
Epilepsy
For monotherapy in adults the CHMP recommended 100 mg to 200 mg a day as the initial dose and a maximum daily dose of 500 mg a day, divided into two doses. The Committee also recommended the initial dose of 100 mg in children aged six years and above.
For adjunctive therapy, the Committee endorsed a dose range for adults of 200 to 400 mg a day, divided into two doses. For children aged two years and above, the Committee recommended a dose of 5 to 9 mg per kilogram body weight a day, divided into two doses.
Migraine
For prevention of migraine in adults, the Committee recommended a total daily dose of 100 mg, divided into two doses. The initial dose should be of 25 mg a day for one week followed by weekly increases of 25 mg until a beneficial dose is reached.

4.3 Contra-indications
The CHMP agreed on a harmonised wording for the contra-indications. Patients who may be hypersensitive (allergic) to the active substance or to any of the other ingredients should not take Topamax.
The Committee did not include a contraindication for the use of Topamax for treating epilepsy in pregnant women or women of childbearing potential who are not using effective methods of contraception. Advice was included in section 4.6 of the SPC about the risks to the mother and the unborn baby of treatment with Topamax.

Other changes
The CHMP harmonised the SPC section on special warnings and included warnings about mood disturbances and depression, suicide and suicidal ideation, and metabolic acidosis (increased acid levels in the body).
The Committee also harmonised the SPC section on the interactions of Topamax with other medicines. The new wording highlights the possibility of reduced effectiveness of oral contraceptives in patients taking Topamax.

The amended information to doctors and patients is available under the "All documents" tabs.

Questions and answers on the referral for Topamax and associated names topiramate tablets and capsules - Final

AdoptedReference Number: EMEA/CHMP/660222/2009

Key facts

About this medicine

• Approved name:
  Topamax
• International non-proprietary name (INN) or common name:
  topiramate

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  CHMP/239500/2009
• 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:
  25/06/2009
• EC decision date:
  01/10/2009

All documents

Topamax - Article 30 referral - Annex I, II, III

AdoptedReference Number: EMEA/CHMP/660222/2009

Questions and answers on the referral for Topamax and associated names topiramate tablets and capsules

AdoptedReference Number: EMEA/CHMP/239500/2009

Questions and answers on the referral for Topamax and associated names topiramate tablets and capsules - Final

AdoptedReference Number: EMEA/CHMP/660222/2009

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.