Download Prescribing Tip No.45 Date: 26th September 2014 Conditions for

Prescribing Tip No.45 Date: 26th September 2014
Conditions for Use of Procoralan® (Ivabradine) to Avoid Potentially Dangerous Bradycardia
The Medicines and Healthcare Products Regulatory Agency (MHRA) have issued a Drug Safety Update1
highlighting emerging clinical trial evidence regarding the use of Ivabadrine to treat the symptoms of long
term stable angina pectoris in adults. It gives recommendations which aim to avoid potentially dangerous
bradycardia.
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Ivabradine is used to treat symptoms of long term stable angina in patients with coronary heart disease who
have a normal heart rhythm. It is also used in patients with long term heart failure who have a normal heart
rhythm but whose heart rate is at least 75 beats per minute (bpm).
The emerging clinical trial evidence relates to the use of ivabradine for patients being treated for chronic
stable angina pectoris only. However, healthcare professionals should take note of the relevant
precautions in the product information, for heart failure, particularly in relation to heart rate.
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The SIGNIFY trial has investigated the efficacy of ivabradine compared to placebo in people with coronary
artery disease. The dose regimen in the trial was higher (7.5 to 10mg twice a day) than the licensed dose (5 to
7.5mg twice a day). The trial included a pre-specified subgroup analysis of participants with symptomatic angina
of CCS class II or more. Preliminary results have shown a small but statistically significant increase in the
combined risk of cardiovascular death or non-fatal myocardial infarction with ivabradine compared with
placebo in this subgroup. The cardiovascular risk may be associated with a target heart rate below 60 bpm.
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The European Medicines Agency is reviewing the balance of benefits and risks of ivabradine in light of these
findings. While the review is ongoing the following advice has been issued by the MHRA:
Advice for healthcare professionals regarding posology and monitoring:
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The starting dose of ivabradine is 5 mg twice daily. The maintenance dose should not exceed 7.5 mg twice daily.
Carefully monitor patients for bradycardia or its symptoms (e.g., dizziness, fatigue and hypotension).
Down-titrate the dose if resting heart rate decreases persistently below 50 bpm or if the patient experiences
symptoms of bradycardia. The dose can be down-titrated to 2.5 mg twice daily if necessary.
Stop ivabradine treatment if the resting heart rate remains below 50 bpm or symptoms of bradycardia persist.
Only increase the dose to 7.5 mg twice daily after 3 to 4 weeks of treatment and if the 5 mg dose is well tolerated
but insufficient. Carefully monitor the effect of a dose increase on heart rate.
Advice to Practices:
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Review the treatment of patients currently using ivabradine, in line with these recommendations, and add prompt
to monitor pulse rate at next patient visit, where appropriate.
Avoid concomitant use of ivabradine with heart rate-reducing calcium channel blockers such as verapamil or
diltiazem.
Further information:
European Medicines Agency statement 8 May 2014
Letter sent to healthcare professionals in June 2014
(111Kb)
Reference:
1. Drug Safety Update volume 7 issue 11, June 2014: S1.accessed at http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON428305