Corlentor and Procoralan

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CHMP opinion
  • European Commission final decision
Current status:
European Commission final decision

Overview

European Medicines Agency recommends measures to reduce risk of heart problems with Corlentor/Procoralan (ivabradine)

On 20 November 2014, the European Medicines Agency (EMA) completed a review of Corlentor/Procoralan (ivabradine) and made recommendations aimed at reducing the risk of heart problems, including heart attack and bradycardia (excessively low heart rate), in patients taking the medicine for angina. Corlentor/Procoralan is used to treat symptoms of angina (chest pain due to problems with the blood flow to the heart) and to treat heart failure.

When used for angina, Corlentor/Procoralan should only be started if the patient's resting heart rate is at least 70 beats per minute (bpm). Because Corlentor/Procoralan has not been shown to provide benefits such as reducing the risk of heart attack or cardiovascular death (death due to heart problems), the medicine should only be used to alleviate symptoms of angina. Doctors should consider stopping treatment if there is no improvement in angina symptoms after 3 months, or if the improvement is only limited.

Other recommendations are that doctors must not prescribe Corlentor/Procoralan together with the medicines verapamil or diltiazem that reduce the heart rate, and that they should monitor their patients for atrial fibrillation (irregular rapid contractions of the upper chambers of the heart). If atrial fibrillation develops during treatment, the balance of benefits and risks of continued Corlentor/Procoralan treatment should be carefully reconsidered.

These recommendations are based on the EMA's review of the final data from the SIGNIFY study1, which showed that in a subgroup of patients who had symptomatic angina there was a small but significant increase in the combined risk of cardiovascular death or non-fatal heart attack with Corlentor/Procoralan compared with placebo (3.4% vs 2.9% yearly incidence rates). The data also indicated a higher risk of bradycardia with Corlentor/Procoralan compared with placebo (17.9% vs. 2.1%).

In its evaluation the EMA also assessed additional data on the safety and effectiveness of Corlentor/Procoralan which showed that the risk of atrial fibrillation is increased in patients treated with Corlentor/Procoralan compared with controls (4.9% vs 4.1%). In the SIGNIFY study, atrial fibrillation was observed in 5.3% of patients taking Corlentor/Procoralan compared with 3.8% in the placebo group.

Patients in the SIGNIFY study were started on a higher than recommended dose of Corlentor/Procoralan and received up to 10 mg twice a day, which is higher than the currently authorised maximum daily dose (7.5 mg twice a day). The EMA considered that the higher dose used in the study did not fully explain the findings. However, the Agency reiterated that the starting dose for angina should not exceed 5 mg twice a day and that the maximum dose should not exceed 7.5 mg twice a day.

The review of Corlentor/Procoralan was first carried out by the EMA's Pharmacovigilance Risk Assessment Committee (PRAC). The PRAC recommendations have been endorsed by the Agency's Committee for Medicinal Products for Human Use (CHMP).

The CHMP opinion was sent to the European Commission, which issued a legally binding decision valid throughout the EU on 15 January 2015.


1Fox K. Ford I, Steg PG, et al. Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med 2014; 371: 1091-9. Available at: http://www.nejm.org/doi/full/10.1056/NEJMoa1406430 (accessed 14/11/14).

Key facts

About this medicine
Approved name
Corlentor and Procoralan
International non-proprietary name (INN) or common name

ivabradine

Associated names
Corlentor and Procoralan
About this procedure
Current status
European Commission final decision
Reference number
EMEA/H/A20/1404/C/000598/0031 EMEA/H/A20/1404/C/000597/0032
Type
Article 20 procedures

This type of procedure is triggered for medicines that have been authorised via the centralised procedure in case of quality, safety or efficacy issues.

Decision making model
PRAC-CHMP-EC
Authorisation model
Centrally authorised product(s)
Key dates and outcomes
Procedure start date
08/05/2014
PRAC recommendation date
06/11/2014
CHMP opinion/CMDh position date
20/11/2014
EC decision date
15/01/2015
Outcome
Risk minimisation measures

All documents

Procedure started

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Opinion provided by Committee for Medicinal Products for Human Use

European Commission final decision

  • List item

    Corlentor and Procoralan Article-20 procedure - European Medicines Agency recommends measures to reduce risk of heart problems with Corlentor/Procoralan (ivabradine) (PDF/104.82 KB)


    First published: 21/11/2014
    Last updated: 16/02/2015
    EMA/35715/2015

  • List item

    Corlentor and Procoralan Article-20 procedure - Annex IV (PDF/57.56 KB)


    First published: 16/02/2015
    Last updated: 16/02/2015

  • List item

    Corlentor Article-20 procedure - Annex III (PDF/329.71 KB)


    First published: 21/11/2014
    Last updated: 16/02/2015

  • List item

    Corlentor and Procoralan Article-20 procedure - European Medicines Agency recommends measures to reduce risk of heart problems with Corlentor/Procoralan (ivabradine) (PDF/104.82 KB)


    First published: 21/11/2014
    Last updated: 16/02/2015
    EMA/35715/2015

  • List item

    Procoralan Article-20 procedure - Annex III (PDF/317.84 KB)


    First published: 21/11/2014
    Last updated: 16/02/2015

  • Document description

    • Annex I - List of the medicines affected by the referral
    • Annex II - Scientific conclusions of the CHMP or CMDh
    • Annex III - Changes to the summary of product characteristics, labelling or package leaflet - available when the CHMP or CMDh recommends changes to the product information. Also includes conditions for lifting of suspensions, if applicable
    • Annex IV - Conditions of the marketing authorisation - available when the CHMP or CMDh recommends other measures to be taken for the marketing authorisation such as safety measures or additional studies
    • Notification - A letter from a Member State, the European Commission or a marketing-authorisation holder requesting the initiation of a referral procedure
    • Rationale for triggering - Background provided by the party triggering the referral explaining the issues leading to the initiation of the procedure
    • PRAC list of questions - Questions agreed by the PRAC requesting further information to evaluate the issues identified
    • PRAC timetable - Timeframe agreed by the PRAC to receive information, assess the issues and adopt a recommendation
    • PRAC / CHMP or CMDh assessment report - The assessment and conclusions of the PRAC and CHMP or CMDh on the issues investigated

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