Drugs List

Therapeutic Indications

Uses

Chronic heart failure with sinus rhythm above 74 bpm
Chronic stable angina (normal sinus rhythm), heart rate > 69bpm

Treatment of chronic stable angina pectoris
Symptomatic treatment of chronic stable angina pectoris in patients with coronary artery disease, with normal sinus rhythm whose heart rate is greater than or equal to 70 beats per minute (bpm), who are either contraindicated for use or intolerant of beta blockers, or in combination with beta blockers in patients inadequately controlled with an optimal beta blocker dose.

Treatment of chronic heart failure
Treatment of chronic heart failure NYHA II to IV class with systolic dysfunction, in patients in sinus rhythm and whose heart rate is greater than or equal to 75 bpm, in combination with standard therapy including beta-blocker therapy or when beta-blocker therapy is contraindicated or not tolerated.

Contraindications

Children under 18 years
Sinus node dysfunction
Systolic blood pressure < 90mmHg
Acute phase of cerebrovascular accident
Bradycardia with pulse rate at rest < 70bpm before treatment of angina
Bradycardia with pulse rate at rest < 75bpm before tx of heart failure
Breastfeeding
Cardiac pacemaker
Cardiogenic shock
Galactosaemia
Long QT syndrome
Myocardial infarction
Pregnancy
Second degree atrioventricular block
Severe hepatic impairment
Sinoatrial exit block
Third degree atrioventricular block
Torsade de pointes
Uncontrolled cardiac failure
Unstable angina

Precautions and Warnings

Family history of long QT syndrome
Females of childbearing potential
Patients over 75 years
Atrial fibrillation
Bradycardia with a pulse rate of 50 bpm
Cardiac arrhythmias
Cardiac conduction defects
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
History of torsade de pointes
Hypotension
Lactose intolerance
Moderate hepatic impairment
New York Heart Association class IV failure
Prior to electrical cardioversion
Renal impairment - creatinine clearance below 15ml/minute
Retinitis pigmentosa

Control cardiac failure before starting treatment
Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
CHF: Treatment to be initiated and supervised by a specialist
Reduce initial dose in the elderly
Contains lactose
Monitor cardiac function by ECG
Monitor ECG in patients at risk of QT prolongation
Monitor for atrial fibrillation
Monitor for syncope and bradycardia
Monitor heart rate
Monitor serum electrolytes
Review treatment if atrial fibrillation occurs
Consider discontinuing if visual function deteriorates unexpectedly
Withhold therapy for 24 hours before elective direct current cardioversion
Angina: Discontinue if no improvement within 3 months
Discontinue if pulse rate < 50 beats per minute persists
Advise patient not to take St John's wort concurrently
Advise patient to avoid grapefruit products
Female: Ensure adequate contraception during treatment

Not recommended in patients with atrial fibrillation or other cardiac arrhythmias which interfere with sinus node function.
Ivabradine loses its efficacy in the presence of a tachyarrhythmia and is not effective in the treatment or prevention of arrhythmias.

Chronic heart failure patients with intraventricular conduction defects (bundle branch block left, bundle branch block right) and ventricular dyssynchrony should be monitored closely.

Not recommended for immediate use following a stroke as there is no data available for these patients.

Ivabradine may cause transient luminous visual effects (mainly phosphenes) which should be taken into account when considering driving or operating machinery or other situations where sudden variations in light intensity may occur.

Pregnancy and Lactation

Pregnancy

Ivabradine is contraindicated in pregnancy.

There is limited data on the use of ivabradine during pregnancy.

Animal studies have shown embryotoxic and teratogenic effects. The human risk is unknown.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Ivabradine is contraindicated in breastfeeding.

Animal studies indicated ivabradine is excreted in the breast milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Angioedema
Asthenia
Atrial extrasystoles
Atrial fibrillation
Blood pressure changes
Blurred vision
Bradycardia
Constipation
Diarrhoea
Diplopia
Dizziness
Dyspnoea
Eosinophilia
Erythema
Fatigue
First degree AV block
Headache
Hyperuricaemia
Hypotension
Malaise
Muscle cramps
Nausea
Palpitations
Phosphenes
Prolongation of QT interval
Pruritus
Rash
Second and third degree AV block
Serum creatinine increased
Sick-sinus syndrome
Syncope
Urticaria
Ventricular extrasystoles
Vertigo
Visual disturbances

Presentation

Oral formulations of ivabradine.

Drugs List

Therapeutic Indications

Uses

Chronic heart failure with sinus rhythm above 74 bpm
Chronic stable angina (normal sinus rhythm), heart rate > 69bpm

Treatment of chronic stable angina pectoris
Symptomatic treatment of chronic stable angina pectoris in patients with coronary artery disease, with normal sinus rhythm whose heart rate is greater than or equal to 70 beats per minute (bpm), who are either contraindicated for use or intolerant of beta blockers, or in combination with beta blockers in patients inadequately controlled with an optimal beta blocker dose.

Treatment of chronic heart failure
Treatment of chronic heart failure NYHA II to IV class with systolic dysfunction, in patients in sinus rhythm and whose heart rate is greater than or equal to 75 bpm, in combination with standard therapy including beta-blocker therapy or when beta-blocker therapy is contraindicated or not tolerated.

Dosage

Adults

Elderly

Contraindications

Children under 18 years
Sinus node dysfunction
Systolic blood pressure < 90mmHg
Acute phase of cerebrovascular accident
Bradycardia with pulse rate at rest < 70bpm before treatment of angina
Bradycardia with pulse rate at rest < 75bpm before tx of heart failure
Breastfeeding
Cardiac pacemaker
Cardiogenic shock
Galactosaemia
Long QT syndrome
Myocardial infarction
Pregnancy
Second degree atrioventricular block
Severe hepatic impairment
Sinoatrial exit block
Third degree atrioventricular block
Torsade de pointes
Uncontrolled cardiac failure
Unstable angina

Precautions and Warnings

Family history of long QT syndrome
Females of childbearing potential
Patients over 75 years
Atrial fibrillation
Bradycardia with a pulse rate of 50 bpm
Cardiac arrhythmias
Cardiac conduction defects
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
History of torsade de pointes
Hypotension
Lactose intolerance
Moderate hepatic impairment
New York Heart Association class IV failure
Prior to electrical cardioversion
Renal impairment - creatinine clearance below 15ml/minute
Retinitis pigmentosa

Control cardiac failure before starting treatment
Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
CHF: Treatment to be initiated and supervised by a specialist
Reduce initial dose in the elderly
Contains lactose
Monitor cardiac function by ECG
Monitor ECG in patients at risk of QT prolongation
Monitor for atrial fibrillation
Monitor for syncope and bradycardia
Monitor heart rate
Monitor serum electrolytes
Review treatment if atrial fibrillation occurs
Consider discontinuing if visual function deteriorates unexpectedly
Withhold therapy for 24 hours before elective direct current cardioversion
Angina: Discontinue if no improvement within 3 months
Discontinue if pulse rate < 50 beats per minute persists
Advise patient not to take St John's wort concurrently
Advise patient to avoid grapefruit products
Female: Ensure adequate contraception during treatment

Not recommended in patients with atrial fibrillation or other cardiac arrhythmias which interfere with sinus node function.
Ivabradine loses its efficacy in the presence of a tachyarrhythmia and is not effective in the treatment or prevention of arrhythmias.

Chronic heart failure patients with intraventricular conduction defects (bundle branch block left, bundle branch block right) and ventricular dyssynchrony should be monitored closely.

Not recommended for immediate use following a stroke as there is no data available for these patients.

Ivabradine may cause transient luminous visual effects (mainly phosphenes) which should be taken into account when considering driving or operating machinery or other situations where sudden variations in light intensity may occur.

Pregnancy and Lactation

Pregnancy

Ivabradine is contraindicated in pregnancy.

There is limited data on the use of ivabradine during pregnancy.

Animal studies have shown embryotoxic and teratogenic effects. The human risk is unknown.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Ivabradine is contraindicated in breastfeeding.

Animal studies indicated ivabradine is excreted in the breast milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Angioedema
Asthenia
Atrial extrasystoles
Atrial fibrillation
Blood pressure changes
Blurred vision
Bradycardia
Constipation
Diarrhoea
Diplopia
Dizziness
Dyspnoea
Eosinophilia
Erythema
Fatigue
First degree AV block
Headache
Hyperuricaemia
Hypotension
Malaise
Muscle cramps
Nausea
Palpitations
Phosphenes
Prolongation of QT interval
Pruritus
Rash
Second and third degree AV block
Serum creatinine increased
Sick-sinus syndrome
Syncope
Urticaria
Ventricular extrasystoles
Vertigo
Visual disturbances

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: September 2018

Reference Sources

Summary of Product Characteristics: Ivabradine 2.5mg tablets. Aspire Pharma Ltd. Revised May 2018.

Summary of Product Characteristics: Procoralan. Servier Laboratories Ltd. Revised October 2021.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 05 September 2018.