ivabradine hydrochloride: clinical use

Prescribing considerations

• Confirm sinus rhythm and establish resting heart rate using serial measurements, ECG or ambulatory monitoring where appropriate.
• For angina, licensing requires a resting heart rate of at least 70 beats per minute; treatment is for symptom control rather than preventing myocardial infarction or cardiovascular death.
• For chronic systolic heart failure, licensing requires stable disease, sinus rhythm and a resting heart rate of at least 75 beats per minute.
• Review renal and hepatic function, rhythm history, blood pressure, concomitant medicines, pregnancy potential and retinal disease.
• Use caution in moderate hepatic impairment, severe renal impairment, mild-to-moderate hypotension, advanced heart failure, conduction defects and retinitis pigmentosa.

Contraindications and cautions

• Resting heart rate below 70 beats per minute before treatment
• Cardiogenic shock, acute myocardial infarction, unstable angina, or unstable or acute heart failure
• Severe hypotension or severe hepatic insufficiency
• Sick sinus syndrome, sino-atrial block or third-degree atrioventricular block
• Pacemaker dependence
• Strong CYP3A4 inhibitors, verapamil or diltiazem
• Pregnancy, breastfeeding, or childbearing potential without appropriate contraception
• Hypersensitivity to ivabradine or product excipients

Monitoring

• Resting heart rate and symptoms of bradycardia
• Pulse and ECG when atrial fibrillation or another rhythm disturbance is suspected
• Angina symptoms or heart-failure status to confirm continuing clinical benefit
• Blood pressure, particularly after changes to antihypertensive treatment
• Visual function if unexpected deterioration occurs
• Electrolytes and ECG risk when potassium-depleting or QT-prolonging medicines are necessary

Clinical pharmacology

Ivabradine selectively inhibits the sinus-node If current. It is metabolised in the gut and liver through CYP3A4 and has an active N-desmethyl metabolite. Food delays absorption but increases exposure and reduces variability. It has no direct negative inotropic effect.

Formulation and product differences

• Selected products are film-coated tablets containing lactose.
• The selected generic higher-strength tablet is white, round and unscored.
• Procoralan tablets are salmon-coloured; its lower-strength tablet is oblong, scored and divisible into equal parts, while its higher-strength tablet is triangular and unscored.
• Tablet appearance, excipients, packaging and splitability vary by product, so check the specific leaflet.

Tablet

Route: Oral

Strengths: 2.5 mg, 5 mg, 7.5 mg