Ikorel and Dancor - referral

Current status

European Commission final decision

Overview

On 26 March 2015, the European Medicines Agency completed a review of Ikorel and Dancor. The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that there is a need to harmonise the prescribing information for these medicines in the European Union (EU).

What are Ikorel and Dancor?

Ikorel and Dancor are medicines used to treat symptoms of angina pectoris (pain in the chest due to problems with the blood flow to the heart) in adult patients for whom treatment with medicines known as beta-blockers and/or calcium antagonists is not sufficiently effective, not indicated or not tolerated.

Ikorel and Dancor contain the active substance nicorandil, which works by relaxing the muscles in the walls of the blood vessels that supply the heart, thereby improving blood flow to the heart muscle and relieving the symptoms of angina.

Ikorel and Dancor are marketed in the following EU Member States: Austria, Denmark, France, Ireland, the Netherlands, Portugal, and the United Kingdom. They are also available in the EU under other trade names: Adancor, Angicor and Nicorandil Zentiva.

The companies that market these medicines are Sanofi-Aventis and Merck KGaA.

Why were Ikorel and Dancor reviewed?

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

Ikorel and Dancor were identified as needing harmonisation by the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh).

On 12 December 2013, the European Commission referred the matter to the CHMP in order to harmonise the marketing authorisations for Ikorel and Dancor 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 indication

The CHMP agreed that Ikorel and Dancor should only be used as a second-line option to treat the symptoms of angina, when patients do not sufficiently respond to, do not tolerate or should not take medicines such as beta-blockers and/or calcium antagonists.

Ikorel and Dancor should no longer be used to prevent heart problems, such as a heart attack, in patients with stable coronary heart disease (heart disease caused by the obstruction of the blood vessels that supply the heart muscle), because the available clinical data do not support this indication.

4.2 Posology and method of administration

Having harmonised the indications, the CHMP also harmonised the recommendations on how to use Ikorel and Dancor. The usual starting dose is 10 mg taken twice a day, preferably in the morning and in the evening. In patients particularly predisposed to headaches, the starting dose can be lowered to 5 mg twice a day. Depending on the patient's response and tolerance to treatment, the dose can be increased up to a maximum of 40 mg twice a day.

4.3 Contraindications

The CHMP agreed that Ikorel and Dancor must not be used in:

• Patients with known hypersensitivity (allergy) to nicorandil or to any of the other ingredients;
• Patients with shock, severe hypotension (low blood pressure), or heart problems such as 'left ventricular dysfunction with low filling pressure' or 'cardiac decompensation';
• Patients taking medicines known as 'phosphodiesterase 5 inhibitors' and/or 'soluble guanylate cyclase stimulators', since this can lead to a serious drop in blood pressure;
• Patients suffering from hypovolaemia (low blood volume);
• Patients with a build-up of fluids in the lungs (acute pulmonary oedema).

4.4 Special warnings and precautions for use

Gastrointestinal ulcers and ulcers on the skin and some internal (mucosal) surfaces have been reported in patients taking Ikorel or Dancor. These ulcers are difficult to treat and usually resolve only when treatment with Ikorel or Dancor is stopped. If ulcers develop, Ikorel or Dancor should be permanently discontinued.

Ikorel and Dancor should be used with caution in patients taking the following medicines:

• Aspirin or medicines called NSAIDs (non-steroid anti-inflammatory drugs), because these patients are at higher risk of developing complications of ulcers, such as bleeding in the stomach or gut;
• Medicines that could increase the levels of potassium in the blood, especially in patients with reduced kidney function;
• Medicines that have a blood pressure-lowering effect.

Additionally, Ikorel and Dancor should be used with caution in patients lacking an enzyme called glucose-6-phosphate dehydrogenase, and in patients with heart failure class III or IV (heart disease that severely limits or makes physical activity not possible without discomfort).

Other changes

The CHMP also harmonised other sections of the SmPC including sections 4.5 (interactions with other medicinal products), 4.8 (undesirable effects) and 5.1 (pharmacodynamic properties). The labelling and package leaflet were also revised in line with the changes to the SmPC.

The European Commission issued an EU-wide legally binding decision to implement these changes on 05 June 2015.

Questions and answers on Ikorel, Dancor and associated names (nicorandil, 10 and 20 mg tablets)

Adopted Reference Number: EMA/199003/2015

Key facts

About this medicine

• Approved name:
  Ikorel and Dancor
• International non-proprietary name (INN) or common name:
  nicorandil
• Class:
  cardiovascular

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-30/1380
• 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:
  26/03/2015
• EC decision date:
  05/06/2015

All documents

Opinion provided by Committee for Medicinal Products for human Use

Ikorel and Dancor Article-30 referral - Annex III

Questions and answers on Ikorel, Dancor and associated names (nicorandil, 10 and 20 mg tablets)

Adopted Reference Number: EMA/199003/2015

European Commission final decision

Ikorel and Dancor Article-30 referral - Annex I

Ikorel and Dancor Article-30 referral - Annex II

Ikorel and Dancor Article-30 referral - Assessment report

Adopted Reference Number: EMA/238211/2015

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.