Dear Healthcare Professional Letter on new contraindications and recommendations for minimising risks from cardiovascular events and severe bradycardia associated with the use of Procoralan and Corlentor (ivabradine)

10.12.2014

Servier Pharma d.o.o., the local marketing authorisation holder’s representative for Procoralan and Corlentor (ivabradine), in agreement with the Agency for Medicinal Products and Medical Devices (HALMED) and the European Medicines Agency (EMA) would like to inform healthcare professionals on the recommendations for use of ivabradine to minimise the risk from cardiovascular events and severe bradycardia.

Summary

In the symptomatic treatment of patients with chronic stable angina, the use of ivabradine should not start before resting heart rate is ≥ 70 bpm
The treatment with ivabradine should be discontinued if angina symptoms do not improve within 3 months
Concomitant use of ivabradine and verapamil or diltiazem is from now on contraindicated.
Before starting the ivabradine treatment or in the case of dose titration, the heart rate should be caeefully monitored, including a serial heart rate measuring, electrocardiogram or 24-hrs monitoring
While on treatment with ivabradine patients should be carefully monitored for the occurrence of atrial fibrillation. If atrial fibrillation occurs during treatment the benefit/risk ratio for the continuation of the ivabradine treatment should be reviewed.

With this letter healthcare professionals are reminded of the following:

Ivabradine is indicated for the symptomatic treatment of chronic stable angina pectoris in adult patients unable to tolerate or with contraindications to the use of beta-blockers or in combination with beta-blockers in patients inadequately controlled with an optimal beta-blocker dose.
The usual recommended starting dose is 5 mg twice daily.
The dose should only be increased to 7.5 mg twice daily after three to four weeks of treatment if the therapeutic response with 5 mg twice daily is insufficient and if the 5 mg dose is well tolerated. The effect of a dose increase on the heart rate should be carefully monitored.
The maintenance dose should not exceed 7.5 mg twice daily
If resting heart rate decreases persistently under 50 bpm during treatment or the patient experiences symptoms related to bradycardia occur the dose must be down-titrated, including the possible dose of 2.5 mg twice daily. After down-titration of the dose, the heart rate should be carefully monitored. If even after the down -titration of the dose the heart rate is under 50 bpm or symptoms related to bradycardia persist, the treatment should be discontinued.

Further information

These recommendations are the outcome of the SIGNIFY study results. The SIGNIFY study evaluated the decrease of ivabradine with regard to placebo the incidents of events such as the stroke in patients suffering from coronary heart disease (heart disease caused by obstruction of blood vessels that supply the heart muscle), without heart failure. The study demonstrated a minor, but significant increase of combined risk from cardiovascular death or non-fatal heart attack with the use of this medicine in certain patients with the symptomatic angina and the data also revealed an increased risk from bradycardia with regard to placebo.

Here you may view the Dear Healthcare Professional Letter.

We remind healthcare professionals that they should report any adverse reaction, as well as quality defect to HALMED. Patients who have developed any adverse reaction to medicinal product may report it directly to HALMED via form or on-line application, with recommendation regarding any adverse reaction they discover to consult their doctor or pharmacist about the continuation of their therapy.