Servier launches novel treatment for chronic stable angina

Servier has launched Procoralan (ivabradine) tablets for the symptomatic treatment of chronic stable angina in patients with normal sinus rhythm and a contraindication or intolerance for ß-blockers.

Legal category: POM.

Brand name: Procoralan

Active ingredient: Ivabradine (as hydrochloride)
5 mg, 7.5 mg.

Description: 5 mg, oblong pink film-coated tablet; 7.5 mg, triangular pink film-coated tablet. Both marked with strength and logo.

Presentation: 5 mg, 56 = £39.00; 7.5 mg, 56 = £39.00.

Indications: Symptomatic treatment of chronic stable angina in patients with normal sinus rhythm, and a contraindication or intolerance for ß-blockers.

Pharmacology: Ischaemic heart disease affects 4% of adults in the UK. As the incidence of this disease has increased, the search for improved therapies has continued. As a result, a new class of compounds, If inhibitors, has been developed for the treatment of stable angina.

Ivabradine is a selective If inhibitor which acts specifically on the sino-atrial node. It inhibits the cardiac pacemaker If current that controls spontaneous diastolic depolarisation leading to a reduction in heart rate. The cardiac effects are specific to the sinus node. Ivabradine has no effect on intra-atrial, atrioventricular or intraventricular conduction times, nor does it alter myocardial contractility or ventricular repolarisation. At usual recommended doses, ivabradine reduces heart rate by approximately 10 bpm at rest and during exercise, resulting in a reduction in cardiac workload and myocardial oxygen consumption.

Following oral administration, ivabradine is rapidly and almost completely absorbed with peak plasma levels attained after approximately one hour. It undergoes extensive hepatic and gastrointestinal metabolism via cytochrome P450 3A4 as does its major active metabolite. Ivabradine is eliminated with a main half-life of two hours in plasma and an effective half-life of 11 hours. Excretion occurs via the faeces and urine.

In large-scale double-blind trials, ivabradine had a significant anti-anginal and anti-ischaemic effect compared with placebo. At doses of 5 mg and 7.5 mg twice daily ivabradine was shown to be effective on exercise parameters within three to four weeks of treatment and was associated with a decrease of about 70% in the rate of angina attacks.

In one multi-centre study of over 900 patients with a three-month history of stable angina and documented coronary artery disease, the efficacy of ivabradine was compared to that of atenolol. After both one month and four months of treatment, all exercise test criteria were similarly improved, including time to limiting angina, time to angina onset and time to 1 mm ST-segment depression. The study did not to reveal any evidence of pharmacological tolerance developing or of rebound phenomena following abrupt discontinuation and, unlike many ß-blockers, ivabradine was not associated with sexual dysfunction, asthenia or bronchospasm.

Adult Dose: Initially, 5 mg twice daily; increase if necessary to 7.5 mg twice daily after three to four weeks depending on therapeutic response. If heart rate decreases to below 50 bpm or with symptoms indicative of bradycardia, titrate dose downward to 2.5 mg twice daily. Dose should be taken morning and evening with meals.

Child Dose: Under 18 years, not recommended.

Contraindications: Resting heart rate below 60 bpm prior to treatment or if heart rate persistently below 50 bpm/persistent signs of bradycardia during treatment. Cardiogenic shock, acute MI, severe hypotension. Sick sinus syndrome, sino-atrial block, heart failure with NYHA class III-IV. Pacemaker dependent, unstable angina, 2nd or 3rd degree AV-block, cardiac arrhythmias. Severe hepatic impairment. Immediately after stroke. Pregnancy, lactation.

Special precautions: Elderly. Mild to moderate hypotension. Renal insufficiency, moderate hepatic impairment. Monitor regularly for atrial fibrillation. QT syndrome or QT prolongation. Asymptomatic left ventricular dysfunction heart failure patients with NYHA functional classification II. Retinitis pigmentosa.

Interactions: CYP3A4 inhibitors, verapamil, diltiazem, QT prolonging medicines, grapefruit juice, CYP3A4 inducers.

Adverse reactions: Luminous phenomena (phosphenes), blurred vision. Bradycardia, 1st degree AV-block, ventricular extrasystoles, headache, dizziness.

? Report any adverse reaction to CSM.

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