- Home
- Medical news & Guidelines
- Anesthesiology
- Cardiology and CTVS
- Critical Care
- Dentistry
- Dermatology
- Diabetes and Endocrinology
- ENT
- Gastroenterology
- Medicine
- Nephrology
- Neurology
- Obstretics-Gynaecology
- Oncology
- Ophthalmology
- Orthopaedics
- Pediatrics-Neonatology
- Psychiatry
- Pulmonology
- Radiology
- Surgery
- Urology
- Laboratory Medicine
- Diet
- Nursing
- Paramedical
- Physiotherapy
- Health news
- Fact Check
- Bone Health Fact Check
- Brain Health Fact Check
- Cancer Related Fact Check
- Child Care Fact Check
- Dental and oral health fact check
- Diabetes and metabolic health fact check
- Diet and Nutrition Fact Check
- Eye and ENT Care Fact Check
- Fitness fact check
- Gut health fact check
- Heart health fact check
- Kidney health fact check
- Medical education fact check
- Men's health fact check
- Respiratory fact check
- Skin and hair care fact check
- Vaccine and Immunization fact check
- Women's health fact check
- AYUSH
- State News
- Andaman and Nicobar Islands
- Andhra Pradesh
- Arunachal Pradesh
- Assam
- Bihar
- Chandigarh
- Chattisgarh
- Dadra and Nagar Haveli
- Daman and Diu
- Delhi
- Goa
- Gujarat
- Haryana
- Himachal Pradesh
- Jammu & Kashmir
- Jharkhand
- Karnataka
- Kerala
- Ladakh
- Lakshadweep
- Madhya Pradesh
- Maharashtra
- Manipur
- Meghalaya
- Mizoram
- Nagaland
- Odisha
- Puducherry
- Punjab
- Rajasthan
- Sikkim
- Tamil Nadu
- Telangana
- Tripura
- Uttar Pradesh
- Uttrakhand
- West Bengal
- Medical Education
- Industry
Ivabradine
Allopathy
Prescription Required
DCGI (Drugs Controller General of India)
Schedule H
Ivabradine is an antianginal belonging to Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers.
Ivabradine is used to reduce the risk of hospitalization for worsening heart failure in adult patients and for treatment of stable symptomatic heart failure because of dilated cardiomyopathy in pediatric patients.
Following oral administration, peak plasma ivabradine concentrations are reached in approximately 1 hour under fasting conditions. The absolute oral bioavailability of Ivabradine is approximately 40% because of first-pass elimination in the gut and liver. Ivabradine is approximately 70% plasma protein bound, and the volume of distribution at steady state is approximately 100 L. Ivabradine is extensively metabolized in the liver and intestines by CYP3A4-mediated oxidation. The N-demethylated derivative is also metabolized by CYP3A4. Ivabradine plasma levels decline with a distribution half-life of 2 hours and an effective half-life of approximately 6 hours. The total clearance of Ivabradine is 24 L/h, and renal clearance is approximately 4.2 L/h, with ~ 4% of an oral dose excreted unchanged in the urine. The excretion of metabolites occurs to a similar extent via feces and urine.
Ivabradine shows common side effects like Nausea, constipation, headache, dizziness, etc.
Ivabradine is available in the form of an Oral Tablet and Oral Solution.
Ivabradine is available in India, the US, the UK, China, Japan, France, Germany, Spain, and Italy.
Ivabradine belonging to the Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers acts as an antianginal agent.
Ivabradine lowers heart rate by selectively inhibiting If channels ("funny channels") in the heart in a concentration-dependent manner without affecting any other cardiac ionic channels (including calcium or potassium). Ivabradine binds by entering and attaching to a site on the channel pore from the intracellular side and disrupts If ion current flow, which prolongs diastolic depolarization, lowering heart rate. The If currents are located in the sinoatrial node and are the home of all cardiac pacemaker activity. Ivabradine, therefore, lowers the pacemaker firing rate, consequently lowering heart rate, and reducing myocardial oxygen demand. This allows for an improved oxygen supply and therefore mitigation of ischemia, allowing for a higher exercise capacity and reduction in angina episodes.
The Data on the Onset of action and Duration of action of Ivabradine is not available.
The Tmax was found within 1-2 hours following the administration.
Ivabradine is available in the form of Oral Tablets and Oral solutions.
Ivabradine Tablet is taken orally usually twice a day.
Ivabradine solution is taken orally usually twice a day. For oral solution, empty the entire contents of ampule(s) into a medication cup; use a calibrated oral syringe to measure the prescribed dose from the medication cup. Discard any unused oral solution. Rinse the oral syringe and medicine cup with warm, running water after use and air dry.
Ivabradine is used to reduce the risk of hospitalization for worsening heart failure in adult patients and for treatment of stable symptomatic heart failure because of dilated cardiomyopathy in pediatric patients.
Ivabradine is an antianginal belonging to Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers.
Ivabradine is a heart rate lowering agent that works through selective and specific inhibition of the cardiac pacemaker If current controls the spontaneous diastolic depolarization in the sinus node and regulates heart rate.
Ivabradine is approved for use in the following clinical indications
- Congestive Heart Failure
Adult Patients
Ivabradine is indicated to reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction ≤ 35%, who are in sinus rhythm with resting heart rate ≥ 70 beats per minute and either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use.
Pediatric Patients
Ivabradine is indicated for the treatment of stable symptomatic heart failure due to dilated cardiomyopathy (DCM) in pediatric patients aged 6 months and older, who are in sinus rhythm with an elevated heart rate.
Although not approved, there have been certain off-label indications. These include
- Stable angina
Angina is a type of chest pain caused by reduced blood flow to the heart. Angina pain is often described as squeezing, pressure, heaviness, tightness, or pain in the chest. Ivabradine is used in the treatment of chronic stable angina (angina that may occur due to physical activity or emotional stress).
- Inappropriate Sinus tachycardia
- Congestive Heart Failure
Adult Dose
Initial dose: 5 mg orally twice a day with meals
Maximum dose: 7.5 mg orally twice a day
Pediatric Dose
6 Months or Older:
Less than 40 kg (oral solution):
Initial dose: 0.05 mg/kg orally twice a day with food; assess the patient at 2-week intervals and adjust dose by 0.05 mg/kg to target a heart rate reduction of at least 20%, based on tolerability.
Maximum dose: 6 months to less than 1 year old: 0.2 mg/kg orally twice a day, up to a total of 7.5 mg orally twice a day; 1 year or older: 0.3 mg/kg orally twice a day, up to a total of 7.5 mg orally twice a day.
40 kg or more (tablets):
Initial dose: 2.5 mg orally twice a day with food; assess the patient at 2-week intervals and adjust dose by 2.5 mg to target a heart rate reduction of at least 20%, based on tolerability.
Maximum dose: 7.5 mg orally twice a day.
- Stable angina (off-label use)
Adults Oral Dose for <75 years of age
Initial: 2.5 to 5 mg twice daily; titrate up in increments of 2.5 mg after 3 to 4 weeks if symptoms persist and heart rate is >60 bpm.
Maximum dose: 7.5 mg twice daily.
Discontinue therapy if angina symptoms do not improve within 3 months of initiation.
- Inappropriate Sinus tachycardia (off-label use)
Adult Oral Dose
Initial: 5 mg twice daily
Maintenance: 7.5 mg twice daily. May also use in combination with a beta-blocker (eg, metoprolol) in patients who are refractory to monotherapy.
Ivabradine is available in various strengths as 5mg, 7.5mg, and 5mg/5mL.
Ivabradine is available in the form of Oral Tablets and Oral solutions.
Do not eat grapefruit or drink grapefruit juice while taking this medication.
Ivabradine is contraindicated in patients with
● Acute decompensated heart failure
● Blood pressure less than 90/50 mmHg
● Sick sinus syndrome, sinoatrial block, or 3rd-degree AV block, unless a functioning demand pacemaker is present
● Resting heart rate less than 60 bpm prior to treatment.
● Severe hepatic impairment.
● Pacemaker dependence (heart rate maintained exclusively by the pacemaker).
● Concomitant use of strong cytochrome P450 3A4 (CYP3A4) inhibitors.
- Fetal Toxicity
Ivabradine may cause fetal toxicity when administered to a pregnant woman based on findings in animal studies. Embryo-fetal toxicity and cardiac teratogenic effects were observed in fetuses of pregnant rats treated during organogenesis at exposures 1 to 3 times the human exposures (AUC0-24hr) at the maximum recommended human dose (MRHD). Advise females to use effective contraception when taking Ivabradine.
- Atrial Fibrillation
Ivabradine increases the risk of atrial fibrillation. In SHIFT, the rate of atrial fibrillation was 5.0% per patient-year in patients treated with Ivabradine and 3.9% per patient-year in patients treated with placebo. Regularly monitor cardiac rhythm. Discontinue Ivabradine if atrial fibrillation develops.
- Bradycardia and Conduction Disturbances
Bradycardia, sinus arrest, and heart block have occurred with Ivabradine. The rate of bradycardia was 6.0% per patient-year in patients treated with Ivabradine (2.7% symptomatic; 3.4% asymptomatic) and 1.3% per patient-year in patients treated with placebo. Risk factors for bradycardia include sinus node dysfunction, conduction defects (e.g., 1st or 2nd-degree atrioventricular block, bundle branch block), ventricular dyssynchrony, and use of other negative chronotropes (e.g., digoxin, diltiazem, verapamil, amiodarone). Concurrent use of verapamil or diltiazem will increase Ivabradine exposure, may themselves contribute to heart rate lowering, and should be avoided. Avoid the use of Ivabradine in patients with 2nd-degree atrioventricular block unless a functioning demand pacemaker is present.
Breast Feeding Warning
There is no information regarding the presence of ivabradine in human milk, the effects of ivabradine on the breastfed infant, or the effects of the drug on milk production. Animal studies have shown, however, that ivabradine is present in rat milk. Because of the potential risk to breastfed infants from exposure to Ivabradine, breastfeeding is not recommended.
Pregnancy Warning
Adverse events have been observed in animal reproduction studies, and fetal harm may occur if ivabradine is administered to pregnant women. If treatment is needed during pregnancy, closely monitor for destabilization of heart failure that could potentially result from heart rate slowing caused by ivabradine, especially during the first trimester. Pregnant women with chronic heart failure should also be monitored for preterm birth.
Food Warning
Do not eat grapefruit or drink grapefruit juice while taking this medication.
- Common Adverse effects
Bradycardia, hypertension, atrial fibrillation, Phosphene, Heart block, and sinoatrial arrest.
- Rare Adverse effects
Angioedema, diplopia, erythema, hypotension, pruritus, skin rash, syncope, torsades de pointes, urticaria, ventricular fibrillation, ventricular tachycardia, vertigo, and visual impairment.
- Bradycardia-Causing Agents: Concurrent use may enhance the bradycardic effect of Ivabradine.
- Clofazimine: Concurrent use may increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
- CYP3A4 Inducers (Moderate): Concurrent use may decrease the serum concentration of Ivabradine.
- CYP3A4 Inducers (Strong): Concurrent use may decrease the serum concentration of Ivabradine.
- CYP3A4 Inhibitors (Moderate): Concurrent use may increase the serum concentration of Ivabradine.
- CYP3A4 Inhibitors (Strong): Concurrent use may increase the serum concentration of Ivabradine.
- Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole and may increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
- Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose.
- Fusidic Acid (Systemic): Concurrent use may increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
- Grapefruit Juice: Concurrent use may increase the serum concentration of Ivabradine.
- Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide.
- Loop Diuretics: Concurrent use may enhance the arrhythmogenic effect of Ivabradine.
- Midodrine: Concurrent use may enhance the bradycardic effect of Bradycardia-Causing Agents.
- Ozanimod: Concurrent use may enhance the bradycardic effect of Bradycardia-Causing Agents.
- Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid the coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm.
- Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid the coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring.
- Thiazide and Thiazide-Like Diuretics: Concurrent use may enhance the arrhythmogenic effect of Ivabradine.
- Tofacitinib: Concurrent use may enhance the bradycardic effect of Bradycardia-Causing Agents.
The common side effects of Ivabradine include the following
● Fast, irregular, or pounding heartbeat, slow or stopped heartbeat, chest pain or pressure, worsening shortness of breath, dizziness, excessive tiredness, lack of energy, swelling of the face, throat, tongue, lips, and eyes, difficulty swallowing or breathing, hoarseness.
- Pregnancy
Pregnancy Category D
Based on findings in animals, Ivabradine may cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of Ivabradine in pregnant women to inform of any drug-associated risks. In animal reproduction studies, oral administration of ivabradine to pregnant rats during organogenesis at a dosage providing 1 to 3 times the human exposure (AUC0-24hr) at the MRHD resulted in embryo-fetal toxicity and teratogenicity manifested as the abnormal shape of the heart, interventricular septal defect, and complex anomalies of primary arteries. Increased postnatal mortality was associated with these teratogenic effects in rats. In pregnant rabbits, increased post-implantation loss was noted at an exposure (AUC0-24hr) 5 times the human exposure at the MRHD. Lower doses were not tested in rabbits. The background risk of major birth defects for the indicated population is unknown. The estimated background risk of major birth defects in the U.S. general population is 2 to 4%, however, and the estimated risk of miscarriage is 15 to 20% in clinically recognized pregnancies. Advise a pregnant woman of the potential risk to the fetus.
- Nursing Mothers
There is no information regarding the presence of ivabradine in human milk, the effects of ivabradine on the breastfed infant, or the effects of the drug on milk production. Animal studies have shown, however, that ivabradine is present in rat milk. Because of the potential risk to breastfed infants from exposure to Ivabradine, breastfeeding is not recommended.
- Pediatric Use
The safety and effectiveness of Ivabradine have been established in pediatric patients (age 6 months to less than 18 years old) and are supported by pharmacokinetic and pharmacodynamic trials and evidence from adequate and well-controlled trials of Ivabradine in adult patients.
- Geriatric Use
No pharmacokinetic differences have been observed in elderly (≥ 65 years) or very elderly (≥ 75 years) patients compared to the overall population. However, Ivabradine has only been studied in a limited number of patients ≥ 75 years of age.
Overdose may lead to severe and prolonged bradycardia. In the event of bradycardia with poor hemodynamic tolerance, temporary cardiac pacing may be required. Supportive treatment, including intravenous (IV) fluids, atropine, and intravenous beta-stimulating agents such as isoproterenol, may be considered.
- Pharmacodynamic
Ivabradine causes a dose-dependent reduction in heart rate. The size of the effect is dependent on the baseline heart rate (i.e., greater heart rate reduction occurs in subjects with a higher baseline heart rate). At recommended doses, the heart rate reduction is approximately 10 bpm at rest and during exercise. Analysis of heart rate reduction vs. dose indicates a plateau effect at doses > 20 mg twice daily. In a study of subjects with preexisting conduction system disease (first- or second-degree AV block or left or right bundle branch block) requiring electrophysiologic study, IV ivabradine (0.20 mg/kg) administration slowed the overall heart rate by approximately 15 bpm, increased the PR interval (29 msec), and increased the AH interval (27 msec). Ivabradine does not have negative inotropic effects. Ivabradine increases the uncorrected QT interval with heart rate slowing but does not cause rate-corrected prolongation of QT.
Pharmacokinetics
- Absorption
Following oral administration, peak plasma ivabradine concentrations are reached in approximately 1 hour under fasting conditions. The absolute oral bioavailability of ivabradine is approximately 40% because of first-pass elimination in the gut and liver.
- Distribution
Ivabradine is approximately 70% plasma protein bound, and the volume of distribution at steady state is approximately 100 L.
- Metabolism and Excretion
Ivabradine is extensively metabolized in the liver and intestines by CYP3A4-mediated oxidation. The major metabolite is the N-desmethylated derivative (S 18982), which is equipotent to ivabradine and circulates at concentrations approximately 40% that of ivabradine. The N-desmethylated derivative is also metabolized by CYP3A4. Ivabradine plasma levels decline with a distribution half-life of 2 hours and an effective half-life of approximately 6 hours. The total clearance of ivabradine is 24 L/h, and renal clearance is approximately 4.2 L/h, with ~ 4% of an oral dose excreted unchanged in the urine. The excretion of metabolites occurs to a similar extent via feces and urine.
1. Koruth JS, Lala A, Pinney S, Reddy VY, Dukkipati SR. The clinical use of ivabradine. Journal of the American College of Cardiology. 2017 Oct 3;70(14):1777-84.
2. Ide T, Ohtani K, Higo T, Tanaka M, Kawasaki Y, Tsutsui H. Ivabradine for the treatment of cardiovascular diseases. Circulation Journal. 2019 Jan 25;83(2):252-60.
3. Annamaria M, Lupo PP, Foresti S, De Ambroggi G, de Ruvo E, Sciarra L, Cappato R, Calo L. Treatment of inappropriate sinus tachycardia with ivabradine. Journal of Interventional Cardiac Electrophysiology. 2016 Jun;46(1):47-53.
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206143orig1s000lbl.pdf
- https://www.rxlist.com/corlanor-drug.htm#medguide
- https://reference.medscape.com/drug/corlanor-ivabradine-999983
- https://www.mims.com/india/drug/info/ivabradine?type=full&mtype=generic
- https://www.drugs.com/dosage/ivabradine.html
- https://go.drugbank.com/drugs/DB09083
- https://medlineplus.gov/druginfo/meds/a615027.html
- https://www.uptodate.com/contents/ivabradine-drug-information#F27975706
- https://www.practo.com/medicine-info/ivabradine-734-api