Ivabradine Zentiva: Uses, Dosage & Side Effects
A selective If channel inhibitor that lowers heart rate for the treatment of chronic stable angina and heart failure in adults
Ivabradine Zentiva is a prescription medication containing ivabradine, a selective and specific inhibitor of the cardiac pacemaker If (funny) current. It works by slowing the heart rate without affecting blood pressure, myocardial contractility, or intracardiac conduction. Ivabradine is used to treat chronic stable angina pectoris in adults whose resting heart rate is 70 beats per minute (bpm) or above, and chronic heart failure (NYHA class II to IV) with systolic dysfunction in patients with a heart rate of 75 bpm or above when beta-blockers alone are insufficient. The landmark SHIFT trial demonstrated that ivabradine significantly reduces cardiovascular death and hospitalization for worsening heart failure, establishing it as a key component of modern heart failure management.
Quick Facts: Ivabradine Zentiva
Key Takeaways
- Ivabradine Zentiva selectively inhibits the If (funny) current in the sinoatrial node, providing pure heart rate reduction without affecting blood pressure, myocardial contractility, or cardiac conduction through other pathways.
- For chronic stable angina, ivabradine is indicated in patients with a resting heart rate of 70 bpm or above who cannot tolerate or have contraindications to beta-blockers, or in combination with beta-blockers when beta-blockers alone are insufficient.
- In chronic heart failure (NYHA II–IV), ivabradine is recommended for patients in sinus rhythm with a heart rate of 75 bpm or above, in combination with standard therapy including maximally tolerated beta-blocker doses.
- The SHIFT trial (n=6,558) demonstrated a 26% relative risk reduction in the composite of cardiovascular death or hospitalization for worsening heart failure with ivabradine versus placebo.
- The most characteristic side effect is luminous phenomena (phosphenes), occurring in approximately 15% of patients, which are typically mild and transient visual brightness sensations that resolve during continued treatment.
What Is Ivabradine Zentiva and What Is It Used For?
Ivabradine Zentiva contains the active substance ivabradine (as ivabradine hydrochloride), which belongs to a unique pharmacological class known as selective If (funny) channel inhibitors. The If current is a mixed sodium-potassium inward current that flows through hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in the sinoatrial (SA) node of the heart. These channels are responsible for the spontaneous diastolic depolarization phase (phase 4) of the SA node action potential, which sets the intrinsic rate of the heartbeat. By selectively and specifically blocking these channels, ivabradine slows the rate of diastolic depolarization and thereby reduces the heart rate.
What makes ivabradine pharmacologically unique among heart rate-lowering agents is its remarkable selectivity for the If current. Unlike beta-blockers, which also reduce heart rate but additionally suppress myocardial contractility, lower blood pressure, and affect bronchial smooth muscle tone, ivabradine exerts its effects exclusively on the SA node pacemaker current. At therapeutic concentrations, ivabradine does not affect intra-atrial conduction time, atrioventricular (AV) conduction, intraventricular conduction, myocardial contractility, or ventricular repolarization. This means that patients taking ivabradine experience a reduction in heart rate without the negative inotropic effects (reduced pumping force), negative dromotropic effects (slowed conduction), or hypotensive effects that accompany beta-blocker therapy.
The heart rate reduction achieved with ivabradine is dose-dependent and correlates with the pre-treatment heart rate. At the recommended therapeutic doses, heart rate is typically reduced by approximately 10 to 15 beats per minute at rest and during exercise. This reduction in heart rate leads to several clinically beneficial effects: it decreases myocardial oxygen demand (because the heart does less work per unit time), it prolongs diastolic perfusion time (allowing more blood to flow through the coronary arteries to nourish the heart muscle), and it improves the balance between myocardial oxygen supply and demand. These properties make ivabradine particularly valuable in two clinical settings.
Chronic Stable Angina Pectoris
Ivabradine is indicated for the symptomatic treatment of chronic stable angina pectoris in adult patients with normal sinus rhythm and a heart rate of at least 70 bpm. In the context of angina, elevated resting heart rate is a well-established risk factor for cardiovascular events. A faster heart rate increases myocardial oxygen consumption and simultaneously reduces the time available for coronary perfusion during diastole. By lowering the heart rate, ivabradine directly addresses these pathophysiological mechanisms. Clinical trials have demonstrated that ivabradine reduces the frequency of angina attacks, decreases the need for short-acting nitrate use, and improves exercise capacity in patients with chronic stable angina.
The BEAUTIFUL trial (morBidity-mortality EvAlUaTion of the If inhibitor ivabradine in patients with coronary disease and left-ventricular dysfunction), a landmark randomized controlled trial involving 10,917 patients with stable coronary artery disease and left ventricular dysfunction, evaluated the long-term effects of ivabradine on cardiovascular outcomes. While the primary composite endpoint was not significantly reduced in the overall population, a pre-specified subgroup analysis of patients with a resting heart rate of 70 bpm or above showed a significant 36% reduction in hospital admissions for myocardial infarction and a 30% reduction in coronary revascularization procedures. These findings reinforced the concept that heart rate reduction with ivabradine provides meaningful cardiovascular protection in patients with elevated resting heart rates.
Chronic Heart Failure
Ivabradine is also indicated for the treatment of chronic heart failure (New York Heart Association functional class II to IV) with systolic dysfunction, in adult patients in sinus rhythm whose resting heart rate is 75 bpm or above, in combination with standard therapy including beta-blockers, or when beta-blockers are contraindicated or not tolerated. In heart failure, an elevated resting heart rate is not merely a marker of disease severity but is itself a therapeutic target. Higher heart rates in heart failure are associated with increased myocardial oxygen consumption, reduced diastolic filling time, impaired coronary perfusion, increased ventricular wall stress, and ultimately worse clinical outcomes.
The SHIFT trial (Systolic Heart failure treatment with the If inhibitor ivabradine Trial) was a pivotal randomized, double-blind, placebo-controlled study that enrolled 6,558 patients with symptomatic heart failure (NYHA class II–IV), a left ventricular ejection fraction (LVEF) of 35% or below, sinus rhythm with a resting heart rate of 70 bpm or above, and at least one hospitalization for worsening heart failure within the previous 12 months. Patients were randomized to receive ivabradine (up-titrated to a maximum of 7.5 mg twice daily) or placebo, in addition to standard heart failure therapy. After a median follow-up of 22.9 months, ivabradine demonstrated a highly significant 18% relative risk reduction (hazard ratio 0.82, 95% CI 0.75–0.90, p < 0.0001) in the primary composite endpoint of cardiovascular death or hospitalization for worsening heart failure. The benefit was primarily driven by a 26% reduction in heart failure hospitalizations. In patients with a baseline heart rate of 75 bpm or above, the results were even more pronounced, with a 24% reduction in the primary composite endpoint and a significant 17% reduction in cardiovascular mortality.
Based on these findings, the European Society of Cardiology (ESC) 2021 guidelines (and the 2023 focused update) recommend ivabradine as a treatment option for patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic with a heart rate of 70 bpm or above despite treatment with an evidence-based dose of a beta-blocker (or when beta-blockers are not tolerated). The American Heart Association/American College of Cardiology (AHA/ACC) guidelines similarly include ivabradine in their heart failure treatment algorithm for patients who meet specific heart rate criteria.
The If current was dubbed the "funny" current by researchers Dario DiFrancesco and colleagues in the 1970s because it was activated by hyperpolarization (becoming more negative) rather than depolarization, which was the opposite of what was expected for most ion channels at the time. This unique current flows through HCN4 channels concentrated in the sinoatrial node and is essential for generating the heart's natural rhythm. By targeting this specific current, ivabradine achieves a unique pharmacological profile: pure heart rate reduction without the additional cardiovascular effects seen with other rate-lowering agents.
What Should You Know Before Taking Ivabradine Zentiva?
Contraindications
Ivabradine is contraindicated in several clinical situations, and it is essential that both patients and prescribers understand these restrictions to ensure safe use. The following conditions represent absolute contraindications to ivabradine therapy:
- Hypersensitivity: Known allergy to ivabradine or any of the excipients in the formulation.
- Resting heart rate below 70 bpm: Before starting treatment, the resting heart rate must be at least 70 bpm. Starting ivabradine in patients with lower heart rates increases the risk of symptomatic bradycardia.
- Cardiogenic shock: Ivabradine must not be used in patients in cardiogenic shock, as further heart rate reduction could worsen hemodynamic instability.
- Acute myocardial infarction: Ivabradine should not be initiated during the acute phase of myocardial infarction due to insufficient safety data in this setting.
- Severe hypotension: Blood pressure below 90/50 mmHg is a contraindication, as the clinical effects of ivabradine have not been adequately studied in this population.
- Severe hepatic insufficiency: Patients with severe liver disease (Child-Pugh class C) must not take ivabradine, as the drug is extensively metabolized in the liver and accumulation may occur.
- Sick sinus syndrome: Ivabradine acts on the SA node and should not be used in patients with dysfunctional sinus node activity.
- Sinoatrial block: Third-degree SA block is a contraindication due to the mechanism of action of ivabradine.
- Unstable or acute heart failure: Ivabradine is indicated only for chronic, stable heart failure and should not be used in acutely decompensated patients.
- Pacemaker dependence: Patients whose heart rate is imposed exclusively by a cardiac pacemaker should not receive ivabradine.
- Unstable angina: Ivabradine is for chronic stable angina only; efficacy and safety in unstable angina have not been established.
- Severe conduction disturbances: Third-degree AV block is a contraindication.
- Concomitant strong CYP3A4 inhibitors: Drugs such as ketoconazole, itraconazole, josamycin, clarithromycin, nefazodone, ritonavir, and nelfinavir significantly increase ivabradine plasma levels and are therefore contraindicated.
- Pregnancy and breastfeeding: Ivabradine is contraindicated during pregnancy and in women of childbearing potential not using effective contraception, as well as during breastfeeding.
Warnings and Precautions
Ivabradine lowers heart rate. If during treatment the resting heart rate falls below 50 bpm, or if the patient experiences symptoms related to bradycardia such as dizziness, fatigue, or hypotension, the dose must be reduced. If the resting heart rate remains below 50 bpm or symptoms of bradycardia persist after dose reduction, treatment must be discontinued.
Before starting and during treatment with ivabradine, the following precautions should be observed:
- Heart rate monitoring: Regular monitoring of resting heart rate is essential. Heart rate should be measured before each dose adjustment and periodically during treatment. Clinical evaluation should include measurement of the resting heart rate by pulse palpation or electrocardiogram (ECG).
- Cardiac arrhythmias: Ivabradine is not effective in the treatment or prevention of cardiac arrhythmias. Its efficacy is reduced when a tachyarrhythmia develops (such as atrial fibrillation or atrial flutter). Ivabradine is not recommended in patients with atrial fibrillation or other cardiac arrhythmias that interfere with sinus node function.
- Atrial fibrillation: There is an increased risk of developing atrial fibrillation during ivabradine treatment. Regular clinical monitoring is recommended, and ivabradine should be discontinued if atrial fibrillation develops during treatment.
- Second-degree AV block: Ivabradine should be used with caution in patients with second-degree AV block.
- QT prolongation: Ivabradine influences the QT interval through its heart rate-lowering effect. While ivabradine does not directly prolong the QT interval, the reduced heart rate may result in a measured QTc prolongation. Caution is advised when combining ivabradine with QT-prolonging medications.
- Visual function: Ivabradine affects retinal function by interacting with Ih current in the retina, which is closely related to the cardiac If current. This may result in transient visual disturbances (phosphenes). Patients who drive or operate machinery at night should exercise caution.
- Hypotension: While ivabradine does not directly lower blood pressure, caution should be exercised in patients with concomitant mild to moderate hypotension due to insufficient clinical data.
- Moderate hepatic impairment: Dose adjustments may be necessary in patients with moderate liver disease (Child-Pugh class B), and these patients should be monitored closely.
Pregnancy and Breastfeeding
Ivabradine is contraindicated during pregnancy. Animal studies have demonstrated reproductive toxicity, including embryotoxic and teratogenic effects at doses close to therapeutic levels. Studies in rats and rabbits have shown that ivabradine can cause cardiac malformations and developmental abnormalities in offspring. There are no adequate and well-controlled studies in pregnant women, and the potential risk to a human fetus is considered unacceptable given the available preclinical data. Women of childbearing potential must use effective contraception during ivabradine treatment. If a patient becomes pregnant while taking ivabradine, the medication must be discontinued immediately and the patient should be referred to her physician for evaluation and alternative treatment options.
Ivabradine is also contraindicated during breastfeeding. Animal studies have shown that ivabradine is excreted in breast milk, and the potential for serious adverse effects in nursing infants cannot be excluded. Mothers taking ivabradine should not breastfeed. If breastfeeding is desired, ivabradine must be discontinued and an alternative treatment option should be discussed with the treating physician. A decision must be made whether to discontinue breastfeeding or to discontinue ivabradine therapy, taking into account the importance of the drug to the mother.
Driving and Operating Machinery
Ivabradine may cause temporary luminous phenomena (phosphenes), which are enhanced visual brightness sensations in a limited area of the visual field. These are typically triggered by sudden changes in light intensity and may occur particularly when driving at night or passing through tunnels. Patients should be aware of this possibility and exercise caution when driving or operating machinery, especially in situations with abrupt changes in light intensity. Apart from phosphenes, ivabradine may also cause blurred vision, which could affect the ability to drive or operate machinery.
How Does Ivabradine Zentiva Interact with Other Drugs?
Understanding ivabradine drug interactions is critical for safe prescribing. Ivabradine is extensively metabolized by cytochrome P450 3A4 (CYP3A4) in both the liver and the intestine. Drugs that significantly inhibit or induce CYP3A4 can therefore have a major impact on ivabradine plasma concentrations and consequently on its clinical effects. Additionally, because ivabradine reduces heart rate, combinations with other heart rate-lowering agents require careful consideration and monitoring.
Contraindicated Combinations
| Drug / Class | Mechanism | Clinical Effect |
|---|---|---|
| Ketoconazole, Itraconazole | Strong CYP3A4 inhibition | Increases ivabradine exposure 7–8 fold; risk of severe bradycardia |
| Ritonavir, Nelfinavir | Strong CYP3A4 inhibition | Greatly increased ivabradine levels; life-threatening bradycardia possible |
| Clarithromycin, Josamycin | Strong CYP3A4 inhibition | Significant increase in ivabradine exposure; excessive heart rate reduction |
| Nefazodone | Strong CYP3A4 inhibition | Markedly increased ivabradine plasma levels |
Not Recommended Combinations
| Drug / Class | Mechanism | Clinical Effect |
|---|---|---|
| Verapamil | Moderate CYP3A4 inhibition + additive heart rate reduction | 2–3 fold increase in ivabradine levels; additional HR-lowering effect; risk of bradycardia |
| Diltiazem | Moderate CYP3A4 inhibition + additive heart rate reduction | Increased ivabradine exposure; enhanced heart rate reduction; risk of symptomatic bradycardia |
| Grapefruit juice | Intestinal CYP3A4 inhibition | Approximately 2-fold increase in ivabradine plasma exposure; avoid consumption during treatment |
Combinations Requiring Caution
| Drug / Class | Mechanism | Clinical Advice |
|---|---|---|
| Beta-blockers | Additive heart rate reduction | Combination is common in HF; monitor heart rate closely; adjust doses to maintain HR above 50 bpm |
| QT-prolonging drugs (amiodarone, sotalol, quinidine) | HR reduction may enhance measured QTc prolongation | Monitor ECG and QTc interval; avoid combination if possible |
| Fluconazole | Moderate CYP3A4 inhibition | Starting dose 2.5 mg twice daily; maximum 5 mg twice daily; monitor heart rate |
| CYP3A4 inducers (rifampicin, phenytoin, carbamazepine, St John’s wort) | Increased ivabradine metabolism | May reduce ivabradine efficacy; dose adjustment may be necessary |
It is important to note that ivabradine does not significantly inhibit or induce CYP450 enzymes itself and is therefore unlikely to affect the metabolism or plasma concentrations of other drugs. In vitro studies have confirmed that ivabradine is not an inhibitor of CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4, and it is not an inducer of CYP3A4. This favorable pharmacokinetic profile means that ivabradine has a relatively low potential for causing drug interactions with medications that are substrates of these enzymes. However, the clinically important interactions described above, particularly with CYP3A4 inhibitors and other heart rate-lowering agents, must always be considered in clinical practice.
Grapefruit juice inhibits intestinal CYP3A4 and approximately doubles ivabradine plasma levels. Patients taking ivabradine should avoid grapefruit juice throughout the duration of treatment. This applies to grapefruit itself as well as grapefruit-containing beverages and products.
What Is the Correct Dosage of Ivabradine Zentiva?
Ivabradine Zentiva tablets should always be taken orally with food, as food increases the absorption of ivabradine by approximately 20–30%. The tablets should be taken twice daily, once in the morning and once in the evening, at approximately the same times each day. Maintaining consistent dosing times helps to maintain steady-state plasma concentrations and ensures reliable heart rate control throughout the day and night.
Adults
Chronic Stable Angina Pectoris
Starting dose: 5 mg twice daily (equivalent to one 5 mg tablet in the morning and one in the evening).
Dose titration: After 3 to 4 weeks of treatment, depending on the therapeutic response and tolerability, the dose may be increased to the maximum dose of 7.5 mg twice daily. If the resting heart rate decreases persistently below 50 bpm during treatment, or if the patient experiences symptoms related to bradycardia (dizziness, fatigue, hypotension), the dose should be reduced to 2.5 mg twice daily (half a 5 mg tablet twice daily). If symptoms do not resolve after dose reduction, treatment should be discontinued.
Discontinuation: Treatment should be discontinued if resting heart rate remains below 50 bpm or if symptoms of bradycardia persist despite dose reduction. Treatment should also be reconsidered if there is no improvement in angina symptoms after 3 months.
Chronic Heart Failure
Starting dose: 5 mg twice daily. Treatment should only be initiated in stable heart failure patients. Heart failure patients should have been on stable doses of standard heart failure medications (including beta-blockers at maximally tolerated dose, or if beta-blockers are contraindicated) for at least 4 weeks before starting ivabradine.
Dose titration: After 2 weeks of treatment at 5 mg twice daily, the dose may be increased to 7.5 mg twice daily if the resting heart rate remains persistently above 60 bpm. Alternatively, if the resting heart rate decreases persistently below 50 bpm, or if the patient experiences symptoms of bradycardia, the dose should be reduced to 2.5 mg twice daily.
Monitoring: If the heart rate is between 50 and 60 bpm, the dose of 5 mg twice daily should be maintained. Treatment should be discontinued if the heart rate remains persistently below 50 bpm or if symptoms of bradycardia persist.
Elderly Patients
In elderly patients (65 years and older), ivabradine should be initiated at a lower starting dose of 2.5 mg twice daily (half a 5 mg tablet twice daily). Dose titration can proceed according to the same principles as in younger adults, with increases after 2 to 4 weeks based on heart rate response and tolerability. Elderly patients may be more susceptible to bradycardia and should be monitored more frequently. The maximum dose of 7.5 mg twice daily can be used in elderly patients if tolerated and clinically indicated.
Children and Adolescents
The safety and efficacy of ivabradine have not been established in children and adolescents under 18 years of age for the treatment of chronic stable angina or chronic heart failure. No data are available, and ivabradine is not recommended for use in this age group for these indications. However, ivabradine has been studied and is used in some countries for the treatment of chronic heart failure due to dilated cardiomyopathy in pediatric patients from 6 months of age, at doses based on body weight (check local prescribing information for specific pediatric dosing guidance).
Renal Impairment
No dose adjustment is required in patients with renal impairment and a creatinine clearance above 15 mL/min. There are insufficient data regarding the use of ivabradine in patients with creatinine clearance below 15 mL/min, and caution should be exercised in these patients.
Hepatic Impairment
No dose adjustment is needed in patients with mild hepatic impairment (Child-Pugh class A). Caution should be exercised in patients with moderate hepatic impairment (Child-Pugh class B), and dose adjustments may be necessary. Ivabradine is contraindicated in patients with severe hepatic impairment (Child-Pugh class C), as this condition has not been studied and a large increase in systemic exposure is expected.
Missed Dose
If you forget to take a dose, take it as soon as you remember, provided it is not close to the time for your next dose. Do not take a double dose to make up for a missed dose. Instead, take the next dose at the usual time and continue with your regular dosing schedule. If you are unsure about what to do, contact your doctor or pharmacist for advice.
Overdose
Overdose with ivabradine may lead to severe and prolonged bradycardia, which can be poorly tolerated. Symptoms of overdose may include severe bradycardia, dizziness, weakness, fatigue, nausea, and syncope (fainting). Treatment of overdose is symptomatic and should take place in a specialized cardiology environment. In cases of bradycardia with poor hemodynamic tolerance, temporary cardiac pacing may be considered. Intravenous isoprenaline (isoproterenol) has been suggested as a potential pharmacological treatment to counteract ivabradine-induced bradycardia in emergency situations, although clinical evidence for this approach is limited. If you suspect an overdose, seek emergency medical attention immediately.
What Are the Side Effects of Ivabradine Zentiva?
Like all medicines, ivabradine can cause side effects, although not everybody gets them. The side effects of ivabradine are generally dose-dependent and related to its pharmacological mechanism of action. Most adverse effects are mild to moderate in intensity and resolve either spontaneously during continued treatment or after dose reduction. The following categorization is based on clinical trial data from the pivotal BEAUTIFUL and SHIFT trials, as well as post-marketing surveillance reports.
Very Common (affects more than 1 in 10 patients)
- Luminous phenomena (phosphenes): Transient enhanced brightness in a limited area of the visual field, typically triggered by sudden changes in light intensity. Reported by approximately 14.5% of patients in clinical trials. Usually mild, occur within the first 2 months of treatment, and resolve spontaneously in most patients during continued therapy. Less than 1% of patients discontinue treatment due to phosphenes.
Common (affects 1 to 10 in 100 patients)
- Bradycardia: Excessively slow heart rate, reported in 3.3% of patients (4.7% in heart failure patients). Symptomatic bradycardia (with dizziness, fatigue, or hypotension) in 0.5–2.2%
- Headache: Usually mild and transient, more common in the first few weeks of treatment
- Dizziness: Related to heart rate reduction; usually dose-dependent
- Blurred vision: May be related to the retinal If/Ih channel interaction
- Atrial fibrillation: Reported in approximately 5% of heart failure patients (vs. 3.8% with placebo in SHIFT trial)
- First-degree AV block (ECG PR prolongation): Usually asymptomatic
- Ventricular extrasystoles: Premature ventricular beats
- Uncontrolled blood pressure: Transient blood pressure changes in some patients
Uncommon (affects 1 to 10 in 1,000 patients)
- Nausea: Mild gastrointestinal discomfort
- Constipation: Occasional bowel changes
- Diarrhea: Usually transient
- Vertigo: Sensation of spinning or loss of balance
- Dyspnea: Shortness of breath, may be related to bradycardia
- Muscle cramps: Involuntary muscle contractions
- Hyperuricemia: Elevated uric acid levels
- Eosinophilia: Increased eosinophil count
- Elevated creatinine: Mild increases in serum creatinine
- Diplopia: Double vision
- Visual impairment: Various other visual disturbances
- Syncope: Fainting, usually related to bradycardia
Rare (affects 1 to 10 in 10,000 patients)
- Skin reactions: Rash, pruritus (itching), urticaria (hives)
- Angioedema: Swelling of the face, lips, tongue, or throat
- Erythema: Skin redness
- Malaise: General feeling of unwellness
Not Known (frequency cannot be estimated from available data)
- Severe skin reactions: Erythema multiforme reported in post-marketing surveillance
- Hepatitis: Isolated cases of liver inflammation reported post-marketing
The visual side effects of ivabradine deserve special attention because they represent a unique pharmacological effect not seen with other cardiac medications. Phosphenes result from the interaction of ivabradine with Ih channels in the retina, which are structurally and functionally related to the cardiac If channels that are the primary therapeutic target. The Ih current in retinal ganglion cells and bipolar cells plays a role in the retinal response to bright light stimuli. When ivabradine partially inhibits these retinal Ih channels, it alters the normal signal processing in the retina, leading to the perception of enhanced brightness, visual sparkles, or stroboscopic effects in response to changes in ambient light levels. These phosphenes are dose-dependent, fully reversible upon discontinuation, and do not cause any structural damage to the retina or visual pathways.
If any side effects become severe, or if you notice any effects not listed above, contact your doctor or pharmacist. Patients should be particularly alert to symptoms of excessive bradycardia (persistent fatigue, dizziness, pre-syncope, or syncope) and should seek medical attention promptly if these occur. New-onset irregular heartbeat should also be reported to the prescribing physician, as this may indicate atrial fibrillation requiring evaluation and possible treatment modification.
Contact your doctor or seek emergency medical care immediately if you experience: persistent dizziness, fainting, or near-fainting episodes; heart rate consistently below 40 bpm; irregular or very slow heartbeat; severe difficulty breathing; signs of an allergic reaction (facial swelling, rash, difficulty breathing); or persistent visual disturbances that interfere with daily activities.
How Should You Store Ivabradine Zentiva?
Proper storage of ivabradine is essential to maintain the stability, efficacy, and safety of the medication throughout its shelf life. Ivabradine Zentiva film-coated tablets should be stored in the original blister packaging to protect them from moisture and light. The tablets do not require refrigeration and can be stored at room temperature, provided the temperature does not exceed 30°C (86°F). Do not store ivabradine in a bathroom or any other humid environment, as moisture can degrade the active ingredient and reduce the effectiveness of the medication.
Keep ivabradine out of the sight and reach of children. Store the medication in a secure location, preferably in a locked cabinet or on a high shelf that children cannot access. Accidental ingestion of ivabradine by a child could cause serious adverse effects, including severe bradycardia. If you suspect that a child has accidentally taken ivabradine, seek emergency medical attention immediately.
Do not use Ivabradine Zentiva after the expiry date stated on the carton and blister after "EXP." The expiry date refers to the last day of that month. Do not dispose of medications via wastewater or household waste. Ask your pharmacist about the correct way to dispose of medicines you no longer use. These measures help to protect the environment and prevent accidental exposure to others.
What Does Ivabradine Zentiva Contain?
The active substance in Ivabradine Zentiva is ivabradine, present in the form of ivabradine hydrochloride. Each 5 mg film-coated tablet contains ivabradine hydrochloride equivalent to 5 mg of ivabradine base. Ivabradine hydrochloride is a white to off-white crystalline powder that is soluble in water and has a molecular weight of approximately 505.1 daltons (as the hydrochloride salt). The chemical name is 3-[3-({[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}(methyl)amino)propyl]-1,3,4,5-tetrahydro-7,8-dimethoxy-2H-3-benzazepin-2-one, hydrochloride.
The other ingredients (excipients) in the tablet core typically include lactose monohydrate (as a filler/diluent), maize starch (as a disintegrant), maltodextrin (as a binder), magnesium stearate (as a lubricant), and colloidal anhydrous silica (as a glidant). The film coating contains hypromellose, titanium dioxide (E171), macrogol 6000, glycerol, magnesium stearate, and iron oxide pigments for coloring. Patients with known intolerance to lactose should be aware that this product contains lactose. The amount of lactose per tablet is generally small, but patients with rare hereditary conditions such as galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should consult their doctor before taking this medicine.
Ivabradine Zentiva 5 mg tablets are typically oval-shaped, salmon/peach-colored film-coated tablets, scored on both sides to allow for dose splitting (to achieve a 2.5 mg dose). The tablets are packaged in PVC/aluminum blisters and are available in various pack sizes depending on the country of marketing, commonly 14, 28, 56, 98, or 112 tablets per box.
Frequently Asked Questions
While both ivabradine and beta-blockers reduce heart rate, they work through fundamentally different mechanisms. Ivabradine selectively inhibits the If (funny) current in the sinoatrial node, providing pure heart rate reduction without affecting blood pressure, myocardial contractility, or bronchial smooth muscle. Beta-blockers block beta-adrenergic receptors throughout the body, which additionally reduces blood pressure, decreases cardiac contractility, and can cause bronchoconstriction. This makes ivabradine particularly useful for patients who cannot tolerate beta-blockers due to hypotension, asthma, or peripheral vascular disease, or as an add-on therapy when beta-blockers alone do not sufficiently control heart rate.
Ivabradine begins to lower heart rate within hours of the first dose, with peak plasma concentrations reached approximately 1 hour after oral administration under fasting conditions (or 2 hours when taken with food, which is the recommended way to take it). However, the full therapeutic effect develops over the first few days to weeks of treatment as steady-state plasma concentrations are achieved (typically within 24 hours for the parent drug). For angina, improvement in exercise tolerance may be noticeable within the first week. For heart failure, clinical studies have shown sustained heart rate reduction from the first assessment time point, but the cardiovascular outcome benefits observed in the SHIFT trial developed over the longer treatment period.
There is no specific contraindication regarding alcohol consumption with ivabradine based on pharmacokinetic drug interaction data. However, excessive alcohol consumption is generally inadvisable for patients with heart failure or coronary artery disease, as alcohol can worsen these conditions. Additionally, alcohol may enhance dizziness, which is a known side effect of ivabradine. Patients with heart failure should follow their doctor's advice regarding alcohol consumption, which is typically to limit or avoid alcohol entirely. If you have questions about alcohol and your medication, consult your doctor or pharmacist.
Transient visual brightness sensations (phosphenes) are a known and expected side effect of ivabradine, experienced by approximately 15% of patients. They are caused by the drug's interaction with channels in the retina that are similar to its target in the heart. Phosphenes are typically triggered by sudden changes in light intensity (such as entering or leaving a tunnel, or bright lights at night) and are usually mild and transient. They do not indicate any damage to your eyes or vision. In most patients, phosphenes resolve spontaneously within the first 2 months of treatment. If the visual effects become bothersome, your doctor may consider reducing the dose. Rarely (less than 1% of patients), phosphenes may lead to treatment discontinuation. However, if you experience persistent visual disturbances, loss of visual acuity, or any unexpected visual changes, consult your doctor for evaluation.
Ivabradine Zentiva, Procoralan, and Corlanor all contain the same active substance, ivabradine, and work in the same way. Procoralan was the original brand-name product developed and marketed by Servier in Europe and many other countries. Corlanor is the brand name used in the United States (marketed by Amgen). Ivabradine Zentiva is a generic version manufactured by Zentiva, which contains the same active ingredient at the same strength and has been approved by regulatory authorities as bioequivalent to the reference product. The clinical efficacy and safety profile are expected to be the same across all ivabradine-containing products, though the excipients (inactive ingredients) and tablet appearance may vary between manufacturers.
Ivabradine should be taken with food because food increases the absorption of the drug by approximately 20–30% compared to taking it on an empty stomach. Additionally, taking ivabradine with meals delays the time to peak plasma concentration from about 1 hour to approximately 2 hours, which results in a smoother pharmacokinetic profile and may reduce the peak-related side effects. This is the way ivabradine was taken in all major clinical trials, so the established efficacy and safety data are based on administration with food. Taking ivabradine consistently with meals also helps establish a routine for twice-daily dosing.
References
- European Medicines Agency (EMA). Ivabradine – Summary of Product Characteristics. Available at: www.ema.europa.eu. Accessed December 2025.
- U.S. Food and Drug Administration (FDA). Corlanor (ivabradine) Prescribing Information. FDA Approved 2015, updated 2024.
- 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
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