Ivabradine Accord
Selective If-Channel Inhibitor for Angina Pectoris and Heart Failure
Quick Facts About Ivabradine Accord
Key Takeaways About Ivabradine Accord
- Unique mechanism of action: Ivabradine is the only medication that selectively lowers heart rate by inhibiting the If current in the sinoatrial node, without affecting blood pressure or contractility
- Proven mortality benefit in heart failure: The SHIFT trial demonstrated that ivabradine reduces cardiovascular death and heart failure hospitalisation in patients with chronic heart failure and elevated heart rate
- Visual side effects are common but harmless: Luminous phenomena (phosphenes) occur in over 10% of patients, especially during the first months of treatment, and resolve upon discontinuation
- Avoid grapefruit juice: Grapefruit juice approximately doubles ivabradine blood levels and must be avoided during treatment
- Contraindicated in pregnancy: Women of childbearing potential must use reliable contraception, as ivabradine has shown teratogenic effects in animal studies
What Is Ivabradine Accord and What Is It Used For?
Ivabradine Accord is a selective heart rate-lowering medication used to treat symptomatic stable angina pectoris in adults with a heart rate of 70 bpm or above, and chronic heart failure (NYHA class II–IV) with systolic dysfunction in adults with a heart rate of 75 bpm or above. It works by selectively inhibiting the cardiac If (funny) current in the sinoatrial node.
Ivabradine belongs to a unique pharmacological class known as selective and specific If-channel inhibitors. The If current (also called the "funny current" because of its unusual electrophysiological properties) is a mixed sodium-potassium inward current that controls the rate of spontaneous diastolic depolarisation in the sinoatrial node – the heart's natural pacemaker. By selectively blocking this current, ivabradine slows the rate at which the sinoatrial node fires, thereby reducing heart rate in a dose-dependent manner.
What makes ivabradine unique among heart rate-lowering drugs is its remarkable selectivity. Unlike beta-blockers, which affect numerous systems throughout the body, ivabradine acts exclusively on the If current. This means it reduces heart rate without lowering blood pressure, without reducing myocardial contractility (the force with which the heart muscle contracts), and without impairing atrioventricular conduction or ventricular repolarisation. This selectivity provides a distinct therapeutic advantage for patients who cannot tolerate the blood pressure-lowering or fatigue-inducing effects of beta-blockers.
Stable Angina Pectoris
Stable angina pectoris (commonly called angina or chest pain) is a heart condition that occurs when the heart muscle does not receive enough oxygen-rich blood. The most common symptom is chest pain or discomfort, typically triggered by physical exertion or emotional stress and relieved by rest. The reduced heart rate achieved with ivabradine decreases the heart's oxygen demand by prolonging diastole (the resting phase between heartbeats), which simultaneously allows more time for coronary blood flow and oxygen delivery to the heart muscle.
Ivabradine is indicated for the symptomatic treatment of stable angina in adult patients with a resting heart rate of 70 beats per minute (bpm) or more. According to the European Society of Cardiology (ESC) 2019 guidelines on chronic coronary syndromes, it can be used in patients who cannot tolerate or have contraindications to beta-blockers, or it can be added to beta-blocker therapy when angina symptoms are not adequately controlled.
Chronic Heart Failure
Chronic heart failure is a progressive condition in which the heart cannot pump enough blood to meet the body's needs. The most common symptoms include breathlessness (dyspnoea), fatigue, reduced exercise tolerance, and swollen ankles (peripheral oedema). In heart failure, an elevated heart rate is associated with poorer outcomes, and reducing heart rate has been shown to improve cardiac function and prognosis.
Ivabradine is indicated for the treatment of chronic heart failure (NYHA class II–IV) with systolic dysfunction in adult patients with a resting heart rate of 75 bpm or more, in combination with standard therapy including beta-blockers, or when beta-blockers are contraindicated or not tolerated. The landmark SHIFT trial (Systolic Heart failure treatment with the If inhibitor ivabradine Trial), published in The Lancet in 2010, demonstrated that ivabradine significantly reduced the composite endpoint of cardiovascular death and hospitalisation for worsening heart failure by 18% compared with placebo.
The specific heart rate-lowering effect of ivabradine helps to: (1) control and reduce the number of angina attacks by decreasing the heart's oxygen demand, and (2) improve cardiac function and long-term prognosis in patients with chronic heart failure. By lowering heart rate, ivabradine allows the heart more time to fill with blood during each heartbeat and reduces the energy the heart needs to function.
What Should You Know Before Taking Ivabradine Accord?
Before starting ivabradine, inform your doctor about all your medical conditions, especially heart rhythm disorders, low blood pressure, liver or kidney problems, and any other medications you are taking. Ivabradine has several absolute contraindications and must not be used during pregnancy or breastfeeding.
Contraindications
You should not take Ivabradine Accord if any of the following apply to you:
- Allergy to ivabradine or any other ingredient in the tablets – symptoms may include rash, itching, swelling, or difficulty breathing
- Resting heart rate below 70 bpm before treatment – ivabradine would lower the heart rate to potentially dangerous levels
- Cardiogenic shock – a severe condition where the heart cannot pump enough blood to meet the body's needs, requiring hospital treatment
- Heart rhythm disorders – including sick sinus syndrome, sinoatrial (SA) block, or third-degree atrioventricular (AV) block
- Acute myocardial infarction (heart attack) – ivabradine should not be initiated during an acute event
- Very low blood pressure (severe hypotension, below 90/50 mmHg) – as the further reduction in heart rate could compromise organ perfusion
- Unstable angina – a serious form of angina where chest pain occurs unpredictably, including at rest
- Recently worsening heart failure – ivabradine should not be started during an acute decompensation episode
- Pacemaker dependency – if your heart rhythm is entirely maintained by a pacemaker
- Severe liver impairment – as ivabradine is extensively metabolised by the liver
- Concurrent use of strong CYP3A4 inhibitors – including ketoconazole, itraconazole, macrolide antibiotics (josamycin, clarithromycin, telithromycin, oral erythromycin), HIV protease inhibitors (nelfinavir, ritonavir), nefazodone, diltiazem, or verapamil
- Pregnancy, planning pregnancy, or breastfeeding – ivabradine is teratogenic in animal studies and passes into breast milk
- Women of childbearing potential not using reliable contraception
Warnings and Precautions
Talk to your doctor or pharmacist before taking Ivabradine Accord if you have or have had any of the following conditions:
- Heart rhythm disorders – such as irregular heartbeat, palpitations, increased chest pain, or sustained atrial fibrillation. Ivabradine is not effective for rate control in atrial fibrillation and its use is not recommended in this condition
- Symptoms of excessive heart rate reduction – such as fatigue, dizziness, or breathlessness, which may indicate that the heart is beating too slowly (bradycardia)
- Atrial fibrillation symptoms – an unusually high resting heart rate (over 110 bpm) or an irregular resting heart rate without an obvious cause
- Recent stroke (cerebrovascular accident) – additional monitoring may be necessary
- Low blood pressure (mild to moderate) – particularly after changes in blood pressure-lowering treatment
- Severe heart failure or bundle branch block on ECG – which may require closer monitoring
- Chronic retinal disease – as ivabradine affects retinal hyperpolarisation-activated (Ih) currents, which may cause visual disturbances
- Moderate liver impairment – dose adjustment may be needed
- Severe kidney impairment – use with caution and close monitoring
Ivabradine Accord must not be given to children or adolescents under 18 years of age. There is insufficient data on safety and efficacy in this age group.
Pregnancy and Breastfeeding
Ivabradine is contraindicated during pregnancy. Animal studies have demonstrated reproductive toxicity, including embryotoxic and teratogenic effects at therapeutic doses. There are no adequate data from the use of ivabradine in pregnant women. If you discover you are pregnant while taking ivabradine, you must stop the medication immediately and contact your doctor.
Women of childbearing potential must use reliable contraception throughout the entire duration of treatment with ivabradine. If you are planning to become pregnant, you should discuss alternative treatments with your doctor before conception.
Ivabradine is contraindicated during breastfeeding. Animal studies indicate that ivabradine is excreted in breast milk. If you are breastfeeding and need treatment with ivabradine, breastfeeding must be discontinued. Discuss the benefits and risks with your doctor.
Driving and Operating Machinery
Ivabradine can cause luminous phenomena (phosphenes) – temporary episodes of enhanced brightness in the visual field, often triggered by sudden changes in light intensity. These visual effects can affect your ability to drive safely, particularly at night. If you experience phosphenes, exercise caution when driving or operating machinery, especially in situations where sudden changes in light intensity may occur, such as driving through tunnels or during nighttime driving.
Important Information About Excipients
Ivabradine Accord tablets contain lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
How Does Ivabradine Accord Interact with Other Drugs?
Ivabradine is metabolised by the CYP3A4 enzyme and has clinically significant interactions with CYP3A4 inhibitors and inducers, as well as QT-prolonging drugs and heart rate-lowering medications. Always inform your doctor about all medications, supplements, and herbal products you are taking.
Ivabradine is extensively metabolised by cytochrome P450 3A4 (CYP3A4) in the liver and intestine. Drugs that inhibit CYP3A4 increase ivabradine blood levels and can lead to excessive bradycardia, while CYP3A4 inducers decrease ivabradine levels and may reduce its therapeutic effect. Additionally, ivabradine should be used with caution alongside other drugs that lower heart rate or prolong the QT interval.
Contraindicated Combinations
| Drug | Category | Effect | Recommendation |
|---|---|---|---|
| Ketoconazole / Itraconazole | Antifungal agents | Strong CYP3A4 inhibitors that can increase ivabradine exposure by 7–8 fold | Combination is contraindicated |
| Clarithromycin / Josamycin / Telithromycin | Macrolide antibiotics | Strong CYP3A4 inhibitors that significantly increase ivabradine levels | Combination is contraindicated |
| Oral Erythromycin | Macrolide antibiotic | Moderate CYP3A4 inhibitor; oral form significantly increases ivabradine exposure | Combination is contraindicated |
| Nelfinavir / Ritonavir | HIV protease inhibitors | Very strong CYP3A4 inhibitors causing dangerous ivabradine accumulation | Combination is contraindicated |
| Nefazodone | Antidepressant | Strong CYP3A4 inhibitor increasing ivabradine levels | Combination is contraindicated |
| Diltiazem / Verapamil | Calcium channel blockers | Moderate CYP3A4 inhibitors with additional heart rate-lowering effect | Combination is contraindicated |
Combinations Requiring Caution
| Drug | Category | Effect | Recommendation |
|---|---|---|---|
| Fluconazole | Antifungal | Moderate CYP3A4 inhibitor; increases ivabradine exposure | Use with caution; starting dose of 2.5 mg twice daily may be needed |
| Rifampicin | Antibiotic (TB treatment) | Strong CYP3A4 inducer; can halve ivabradine blood levels | Dose adjustment of ivabradine may be needed |
| Phenytoin / Barbiturates | Anti-epileptic drugs | CYP3A4 inducers that decrease ivabradine levels | Monitor heart rate; dose increase may be required |
| St John’s Wort (Hypericum perforatum) | Herbal supplement | CYP3A4 inducer that reduces ivabradine effectiveness | Avoid concurrent use or monitor carefully |
| Quinidine / Disopyramide / Amiodarone / Sotalol | Antiarrhythmic drugs | QT-prolonging effect; additive risk when combined with ivabradine | Use with caution; ECG monitoring recommended |
| Pimozid / Ziprasidone / Sertindole | Antipsychotics | QT-prolonging drugs that increase cardiac risk | Avoid combination if possible; close monitoring required |
| Mefloquine / Halofantrine | Antimalarial drugs | QT-prolonging effect with additive cardiac risk | Monitor ECG if concurrent use is unavoidable |
| Furosemide / Hydrochlorothiazide / Indapamide | Diuretics | Potassium-depleting diuretics may increase risk of arrhythmias | Monitor potassium levels; correct hypokalaemia before starting ivabradine |
Grapefruit juice is a CYP3A4 inhibitor that can approximately double ivabradine blood levels. You must avoid grapefruit juice throughout your treatment with Ivabradine Accord. This includes fresh grapefruit, grapefruit juice, and grapefruit-containing products.
What Is the Correct Dosage of Ivabradine Accord?
The usual starting dose is 5 mg twice daily, taken with meals. Your doctor may increase the dose to 7.5 mg twice daily based on your heart rate response. Always take Ivabradine Accord exactly as prescribed by your doctor – do not change the dose without medical advice.
Ivabradine Accord should always be taken during meals, as food increases the absorption and bioavailability of the drug. The tablets should be taken at approximately 12-hour intervals – one in the morning and one in the evening.
Dosage for Stable Angina Pectoris
Adults with Stable Angina
Starting dose: 5 mg twice daily (one tablet in the morning and one in the evening with meals).
After 3–4 weeks, if angina symptoms persist and the 5 mg dose is well tolerated, the dose may be increased to 7.5 mg twice daily.
Maximum dose: 7.5 mg twice daily.
If the heart rate drops below 50 bpm at rest, or if symptoms of bradycardia occur (dizziness, fatigue, hypotension), the dose should be reduced, including to 2.5 mg twice daily (half a 5 mg tablet) if necessary. Treatment should be discontinued if the heart rate remains below 50 bpm or symptoms of bradycardia persist despite dose reduction.
Dosage for Chronic Heart Failure
Adults with Chronic Heart Failure
Starting dose: 5 mg twice daily (one tablet in the morning and one in the evening with meals).
After two weeks of treatment, if the resting heart rate is persistently above 60 bpm, the dose may be increased to 7.5 mg twice daily.
Maximum dose: 7.5 mg twice daily.
If the resting heart rate decreases persistently below 50 bpm or the patient experiences symptoms related to bradycardia, the dose should be reduced to 2.5 mg twice daily. If the heart rate remains below 50 bpm or symptoms persist, treatment must be discontinued.
Elderly Patients
In patients aged 75 years or older, a lower starting dose should be considered: 2.5 mg twice daily (half a 5 mg tablet taken twice daily). The dose can then be increased based on tolerability and heart rate response. Elderly patients are more susceptible to bradycardia and should be monitored closely.
Missed Dose
If you forget to take a dose of Ivabradine Accord, take the next dose at the usual scheduled time. Do not take a double dose to make up for a forgotten one. The calendar printed on the blister pack can help you remember when you last took a tablet.
Overdose
A large dose of Ivabradine Accord may cause severe, prolonged bradycardia (very slow heart rate), which can lead to breathlessness, extreme fatigue, dizziness, or fainting. If you suspect an overdose, contact your doctor or go to the nearest emergency department immediately. Severe bradycardia may require treatment with intravenous isoprenaline or temporary cardiac pacing.
Stopping Treatment
Treatment for stable angina or chronic heart failure is usually long-term. Do not stop taking Ivabradine Accord without consulting your doctor, even if you feel well. Sudden discontinuation may lead to worsening of your symptoms. Your doctor will advise you on whether and how to safely stop the medication, which may involve a gradual dose reduction.
If you feel that the effect of Ivabradine Accord is too strong or too weak, speak to your doctor or pharmacist. Your dose may need to be adjusted.
What Are the Side Effects of Ivabradine Accord?
The most common side effects of ivabradine are luminous phenomena (visual disturbances caused by phosphenes), affecting more than 1 in 10 patients, and bradycardia (slow heart rate). Most side effects are dose-dependent and related to the drug's mechanism of action.
Like all medicines, Ivabradine Accord can cause side effects, although not everybody gets them. The side effects listed below are categorised by how frequently they occur. If you experience any severe or persistent side effects, or any symptoms not listed here, contact your doctor immediately.
Severe dizziness or fainting (may indicate dangerously slow heart rate), severe chest pain, irregular heartbeat, difficulty breathing, sudden swelling of the face, tongue, or throat (angioedema), or severe skin reactions.
Very Common
- Luminous phenomena (phosphenes) – brief episodes of enhanced brightness in the visual field, often triggered by sudden changes in light conditions. They may be described as a halo of light, coloured flashes, image decomposition, or multiple images. They typically appear within the first two months of treatment and may recur. Phosphenes are generally mild to moderate in intensity and resolve spontaneously during or after treatment
Common
- Bradycardia – slow heart rate, particularly in the first 2–3 months of treatment
- Atrial fibrillation – irregular, rapid contraction of the heart's upper chambers
- Abnormal heart rhythm perception – including ventricular extrasystoles and first-degree AV block (prolonged PR interval on ECG)
- Uncontrolled blood pressure
- Headache
- Dizziness
- Blurred vision
Uncommon
- Palpitations and extra heartbeats
- Nausea, constipation, diarrhoea, abdominal pain
- Vertigo (spinning sensation)
- Dyspnoea (breathlessness)
- Muscle spasms
- Elevated uric acid levels in the blood
- Eosinophilia (increase in a type of white blood cell)
- Elevated blood creatinine levels
- Skin rash
- Angioedema (swelling of the face, tongue, or throat)
- Low blood pressure (hypotension)
- Syncope (fainting)
- Fatigue and weakness
- Abnormal ECG pattern
- Double vision (diplopia)
- Visual impairment
Rare and Very Rare
- Rare: Urticaria (hives), pruritus (itching), erythema (skin redness), malaise (general feeling of being unwell)
- Very rare: Second-degree AV block, third-degree AV block, sick sinus syndrome
If you experience any side effects, including those not listed above, you can report them to your national medicines regulatory authority. Reporting side effects helps to continuously monitor the benefit-risk balance of medicines. In the UK, reports can be made via the Yellow Card Scheme. In the EU, contact your national competent authority. In the US, contact the FDA MedWatch programme.
How Should You Store Ivabradine Accord?
Store Ivabradine Accord at or below 30°C (86°F) in the original packaging. Keep out of the sight and reach of children. Do not use after the expiry date printed on the carton and blister.
Proper storage of medications is essential to ensure they remain safe and effective. Follow these guidelines for storing Ivabradine Accord:
- Temperature: Store at or below 30°C (86°F). Do not freeze
- Keep out of reach of children: Store the tablets in a safe place where children cannot see or reach them
- Expiry date: Do not use the tablets after the expiry date (EXP) printed on the carton and blister pack. The expiry date refers to the last day of that month
- Disposal: Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer need. These measures help protect the environment
What Does Ivabradine Accord Contain?
The active substance is ivabradine (as hydrochloride). Each 5 mg tablet contains 5 mg ivabradine, and each 7.5 mg tablet contains 7.5 mg ivabradine. The tablets contain lactose and various film-coating excipients.
Active Ingredient
The active substance is ivabradine, present as ivabradine hydrochloride. Ivabradine hydrochloride is a white to slightly yellowish crystalline powder that is freely soluble in water. Each film-coated tablet contains either 5 mg or 7.5 mg of ivabradine (corresponding to 5.39 mg or 8.085 mg of ivabradine hydrochloride, respectively).
Inactive Ingredients (Excipients)
The other ingredients are:
- Tablet core: Lactose anhydrous, magnesium stearate (E470b), pregelatinised starch (maize), colloidal anhydrous silicon dioxide (E551)
- Film coating: Polyvinyl alcohol (E1203), titanium dioxide (E171), macrogol 4000, talc (E553b), yellow iron oxide (E172), red iron oxide (E172)
Tablet Appearance and Packaging
5 mg tablets: Salmon-coloured, oblong, film-coated tablets with a score line on both sides, debossed with "FK" on one side and "2" on the other side. The score line allows the tablet to be divided into equal halves.
7.5 mg tablets: Salmon-coloured, triangular, film-coated tablets debossed with "FK" on one side and "1" on the other side.
The tablets are available in aluminium/aluminium perforated unit dose blisters in pack sizes of 14, 28, 56, 84, 98, 100, or 112 tablets. Not all pack sizes may be marketed in your country.
Marketing Authorisation Holder and Manufacturer
Ivabradine Accord is manufactured by Accord Healthcare and is authorised for use throughout the European Union. It is a generic equivalent of the originator product and contains the same active substance at the same strength, meeting identical quality and bioequivalence standards.
How Does Ivabradine Work in the Body?
Ivabradine selectively inhibits the If (funny) current in the sinoatrial node, the heart's natural pacemaker. This reduces the rate of spontaneous diastolic depolarisation, lowering heart rate without affecting blood pressure, contractility, or cardiac conduction.
The If current (where "f" stands for "funny") is a mixed sodium-potassium inward current that flows through HCN (hyperpolarisation-activated cyclic nucleotide-gated) channels. These channels are predominantly expressed in the sinoatrial node, where they play a critical role in initiating each heartbeat. During the diastolic (resting) phase between heartbeats, the If current causes a slow, spontaneous depolarisation of sinoatrial node cells, which eventually triggers the next action potential and heartbeat.
Ivabradine binds to the intracellular side of the HCN4 channel (the predominant isoform in the sinoatrial node) in a use-dependent and voltage-dependent manner. By blocking the If current, ivabradine slows the rate of diastolic depolarisation, which delays the time to reach the threshold for the next action potential. The net result is a dose-dependent reduction in heart rate.
At therapeutic doses, ivabradine typically reduces resting heart rate by approximately 10–15 beats per minute at rest and during exercise. This heart rate reduction is achieved without any effect on:
- Blood pressure – unlike beta-blockers, ivabradine does not lower blood pressure
- Myocardial contractility – the force of heart muscle contraction is preserved
- Atrioventricular conduction – the electrical signal travels normally from the atria to the ventricles
- Ventricular repolarisation – the QT interval is not significantly affected at therapeutic doses
- Intracardiac conduction times – the PR, QRS, and corrected QT intervals are unchanged
Pharmacokinetic Profile
Ivabradine is rapidly and almost completely absorbed after oral administration, with peak plasma levels reached in approximately 1 hour under fasting conditions. The absolute oral bioavailability is approximately 40% due to extensive first-pass metabolism in the gut wall and liver, primarily via the CYP3A4 enzyme system.
Food delays absorption by approximately 1 hour and increases plasma exposure by 20–30%, which is why ivabradine should be taken with meals. Plasma protein binding is approximately 70%. The main active metabolite is S 18982 (N-desmethyl ivabradine), which accounts for approximately 40% of the total pharmacological activity.
The plasma elimination half-life of ivabradine is approximately 2 hours, but the effective half-life (considering the contribution of the active metabolite) is approximately 11 hours. Ivabradine is eliminated as metabolites via both renal (approximately 4% of the dose is excreted unchanged in urine) and faecal routes in roughly equal proportions.
Frequently Asked Questions About Ivabradine Accord
Ivabradine Accord is used to treat two cardiovascular conditions: symptomatic stable angina pectoris (chest pain) in adults with a heart rate of 70 bpm or above, and chronic heart failure (NYHA class II–IV) with systolic dysfunction in adults with a heart rate of 75 bpm or above. For angina, it is used when beta-blockers cannot be tolerated or as add-on therapy. For heart failure, it is used in combination with standard treatment.
Luminous phenomena (phosphenes) are the most common side effect of ivabradine, occurring in more than 10% of patients. They are brief episodes of enhanced brightness in the visual field, often described as a halo of light, coloured flashes, or image decomposition. They are typically triggered by sudden changes in light intensity and are most common during the first two months of treatment. Phosphenes are caused by ivabradine's effect on retinal Ih channels (similar to cardiac If channels). They are generally harmless and reversible – they resolve on their own during treatment or after stopping the medication. However, if they significantly affect your daily activities, especially driving at night, discuss this with your doctor.
Yes, ivabradine can be taken together with beta-blockers and is commonly prescribed in combination for both stable angina and chronic heart failure. For angina, ivabradine can be added when beta-blockers alone do not adequately control symptoms. For heart failure, combination therapy is part of the recommended standard of care according to ESC guidelines. However, your doctor will monitor your heart rate carefully, as both medications lower heart rate and the combination may increase the risk of bradycardia.
Although both ivabradine and beta-blockers reduce heart rate, they work through entirely different mechanisms. Beta-blockers block the effects of adrenaline (epinephrine) and noradrenaline on beta-adrenergic receptors throughout the body, reducing heart rate, blood pressure, and the force of heart contraction. Ivabradine, by contrast, selectively inhibits the If current in the sinoatrial node, reducing heart rate without affecting blood pressure, contractility, or cardiac conduction. This makes ivabradine a valuable alternative for patients who cannot tolerate beta-blockers due to side effects such as fatigue, low blood pressure, bronchospasm, or erectile dysfunction.
Ivabradine should be taken during meals because food increases the absorption and bioavailability of the drug by 20–30%. Taking ivabradine with food also helps to reduce the peak plasma concentration, leading to a more stable drug level throughout the day and potentially reducing side effects. The tablets should be taken at approximately 12-hour intervals – one with breakfast and one with dinner – for optimal heart rate control throughout the day and night.
No, ivabradine is strictly contraindicated during pregnancy. Animal studies have shown embryotoxic and teratogenic effects at therapeutic doses. There are insufficient human data to establish safety. Women of childbearing potential must use effective contraception throughout treatment. If you discover that you are pregnant while taking ivabradine, stop the medication immediately and contact your doctor. Ivabradine is also contraindicated during breastfeeding, as it is excreted in breast milk in animal studies.
References
- European Medicines Agency (EMA). Ivabradine – Summary of Product Characteristics. EMA/CHMP. Available at: ema.europa.eu
- Swedberg K, Komajda M, Böhm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. The Lancet. 2010;376(9744):875–885. doi:10.1016/S0140-6736(10)61198-1
- Fox K, Ford I, Steg PG, et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. The Lancet. 2008;372(9641):807–816. doi:10.1016/S0140-6736(08)61170-8
- McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal. 2021;42(36):3599–3726. doi:10.1093/eurheartj/ehab368
- Knuuti J, Wijns W, Saraste A, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. European Heart Journal. 2020;41(3):407–477. doi:10.1093/eurheartj/ehz425
- National Institute for Health and Care Excellence (NICE). Ivabradine for treating chronic heart failure. Technology appraisal guidance [TA267]. 2012 (updated 2024).
- World Health Organization. WHO Model List of Essential Medicines – 23rd List. Geneva: WHO; 2023.
- British National Formulary (BNF). Ivabradine. NICE/BNF. Available at: bnf.nice.org.uk
- DiFrancesco D. The role of the funny current in pacemaker activity. Circulation Research. 2010;106(3):434–446. doi:10.1161/CIRCRESAHA.109.208041
- Tardif JC, Ford I, Tendera M, et al. Efficacy of ivabradine, a new selective If inhibitor, compared with atenolol in patients with chronic stable angina. European Heart Journal. 2005;26(23):2529–2536. doi:10.1093/eurheartj/ehi586
Editorial Team
This article was written by the iMedic Medical Editorial Team, comprising licensed physicians and pharmacologists with specialist expertise in cardiology and clinical pharmacology. All content is based on peer-reviewed clinical evidence and international treatment guidelines.
All content has been independently reviewed by the iMedic Medical Review Board, which includes board-certified cardiologists and clinical pharmacologists. Our review process follows the GRADE evidence framework and adheres to international medical editorial standards.
iMedic is committed to providing accurate, unbiased, and accessible medical information. We receive no pharmaceutical company funding or sponsorship, and all our content is developed independently. For more information, visit our Editorial Standards page.