Corlanor
ivabradine · Tablet, Film Coated · Oral
Uses
1. INDICATIONS AND USAGE Corlanor (ivabradine) is a hyperpolarization-activated cyclic nucleotide-gated channel blocker indicated: To reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure with reduced left ventricular ejection fraction. ( 1.1 ) For the treatment of stable symptomatic heart failure due to dilated cardiomyopathy in pediatric patients ages 6 months and older. ( 1.2 ) 1.1 Heart Failure in Adult Patients Corlanor 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. 1.2 Heart Failure in Pediatric Patients Corlanor 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.
Dosage and administration
2. DOSAGE AND ADMINIST R ATION Adult and pediatric patients greater than 40 kg Starting dose is 2.5 (pediatrics and vulnerable adults) or 5 mg twice daily with food. After 2 weeks of treatment, adjust dose based on heart rate. The maximum dose is 7.5 mg twice daily. ( 2.1 ) Pediatric patients less than 40 kg Starting dose is 0.05 mg/kg twice daily with food. Adjust dose at two-week intervals by 0.05 mg/kg based on heart rate. Maximum dose is 0.2 mg/kg (patients 6 months to less than 1 year old) or 0.3 mg/kg (patients 1 year old and older), up to a total of 7.5 mg twice daily. 2.1 Adults The recommended starting dose of Corlanor is 5 mg twice daily with food. Assess patient after two weeks and adjust dose to achieve a resting heart rate between 50 and 60 beats per minute (bpm) as shown in Table 1. Thereafter, adjust dose as needed based on resting heart rate and tolerability. The maximum dose is 7.5 mg twice daily. In adult patients unable to swallow tablets, Corlanor oral solution can be used [see Clinical Pharmacology ( 12.3 )]. In patients with a history of conduction defects or other patients in whom bradycardia could lead to hemodynamic compromise, initiate therapy at 2.5 mg twice daily before increasing the dose based on heart rate [see Warnings and Precautions ( 5.3 )]. Table 1. Dose Adjustment for Adults Heart Rate Dose Adjustment > 60 bpm Increase dose by 2.5 mg (given twice daily) up to a maximum dose of 7.5 mg twice daily 50-60 bpm Maintain dose < 50 bpm or signs and symptoms of bradycardia Decrease dose by 2.5 mg (given twice daily); if current dose is 2.5 mg twice daily, discontinue therapy* * [ see Warnings and Precautions ( 5.3 )] 2.2 Pediatric Patients Recommended Dosage Pediatric Patients 6 Months of Age and Older Weighing Less than 40 kg (Oral Solution) The recommended starting dose of Corlanor oral solution in pediatric patients 6 months of age and older and weighing less than 40 kg is 0.05 mg/kg twice daily with food. Assess patient at two-week intervals and adjust dose by 0.05 mg/kg to target a heart rate (HR) reduction of at least 20%, based on tolerability. The maximum dose is 0.2 mg/kg twice daily for patients 6 months to less than 1 year old, and 0.3 mg/kg twice daily for patients 1 year old and older, up to a total of 7.5 mg twice daily. If a dose of Corlanor is missed or spit out, do not give another dose to make up for the missed or spit out dose. Give the next dose at the usual time. Pediatric Patients Weighing 40 kg and Greater (Tablets) The recommended starting dose of Corlanor tablets in pediatric patients weighing more than 40 kg is 2.5 mg twice daily with food. Assess patient at two-week intervals and adjust dose by 2.5 mg to target a heart rate (HR) reduction of at least 20%, based on tolerability. The maximum dose is 7.5 mg twice daily. In patients unable to swallow tablets, Corlanor oral solution can be used. Dose Reduction for Bradycardia If bradycardia develops, reduce the dose to the previous titration step. In patients who develop bradycardia at the recommended initial dosage, consider reducing the dosage to 0.02 mg/kg twice daily. Oral Solution Preparation and Administration To administer Corlanor oral solution, empty the entire contents of the ampule(s) into a medication cup. With a calibrated oral syringe, measure the prescribed dose of Corlanor from the medication cup and administer the drug orally. Corlanor oral solution is sterile and preservative-free. Discard the unused oral solution. Do not store or reuse any oral solution left in either the medication cup or an ampule.
Dosage forms and strengths
3. DOSAGE FORMS AND STRENGT HS Corlanor Tablets 5 mg: salmon-colored, oval-shaped, film-coated tablet, functionally scored on both edges, debossed with “5” on one face and bisected on the other face. The tablet is scored and can be divided into equal halves to provide a 2.5 mg dose. 7.5 mg: salmon-colored, triangular-shaped, film-coated tablet debossed with “7.5” on one face and plain on the other face. Corlanor Oral Solution Corlanor 5 mg/5 mL (1 mg/mL) oral solution is a colorless liquid in an opaque, plastic, ampule containing 5 mg of Corlanor in 5 mL of liquid. Tablets: 5 mg, 7.5 mg ( 3 ) Oral Solution: 5 mg/5 mL (1 mg/mL) ( 3 )
Contraindications
4. CONTRAINDICATIONS Corlanor is contraindicated in patients with:
• Acute decompensated heart failure
• Clinically significant hypotension
• Sick sinus syndrome, sinoatrial block or 3 rd degree AV block, unless a functioning demand pacemaker is present
• Clinically significant bradycardia [see Warnings and Precautions ( 5.3 )]
• Severe hepatic impairment [see Use in Specific Populations ( 8.6 )]
• Pacemaker dependence (heart rate maintained exclusively by the pacemaker) [see Drug Interactions ( 7.3 )]
• Concomitant use of strong cytochrome P450 3A4 (CYP3A4) inhibitors [see Drug Interactions ( 7.1 )] Acute decompensated heart failure ( 4 ) Clinically significant hypotension ( 4 ) Sick sinus syndrome, sinoatrial block or 3 rd degree AV block, unless a functioning demand pacemaker is present ( 4 ) Clinically significant bradycardia ( 4 ) Severe hepatic impairment ( 4 ) Heart rate maintained exclusively by the pacemaker ( 4 ) In combination with strong cytochrome CYP3A4 inhibitors ( 4 )
Warnings and precautions
5. WARNINGS AND PRECAUTIONS Fetal toxicity: Females should use effective contraception. ( 5.1 ) Monitor patients for atrial fibrillation. ( 5.2 ) Monitor heart rate decreases and bradycardia symptoms during treatment. ( 5.3 ) Not recommended in patients with 2 nd degree AV block. ( 5.3 ) 5.1 Fetal Toxicity Corlanor 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 (AUC 0-24hr ) at the maximum recommended human dose (MRHD) [see Use in Specific Populations ( 8.1 )] . Advise females of reproductive potential to use effective contraception when taking Corlanor [see Use in Specific Populations ( 8.3 )] . 5.2 Atrial Fibrillation Corlanor increases the risk of atrial fibrillation. In the Systolic Heart Failure Treatment with the I f Inhibitor Ivabradine Trial (SHIFT), the rate of atrial fibrillation was 5.0% per patient-year in patients treated with Corlanor and 3.9% per patient-year in patients treated with placebo [see Clinical Studies ( 14 )] . Regularly monitor cardiac rhythm. Discontinue Corlanor if atrial fibrillation develops. 5.3 Bradycardia and Conduction Disturbances Adult Patients Bradycardia, sinus arrest, and heart block have occurred with Corlanor. The rate of bradycardia was 6.0% per patient-year in patients treated with Corlanor (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., 1 st or 2 nd degree atrioventricular block, bundle branch block), ventricular dyssynchrony, and use of other negative chronotropes (e.g., digoxin, diltiazem, verapamil, amiodarone). Bradycardia may increase the risk of QT prolongation which may lead to severe ventricular arrhythmias, including torsade de pointes, especially in patients with risk factors such as use of QTc prolonging drugs [see Adverse Reactions ( 6.2 )] . Concurrent use of verapamil or diltiazem will increase Corlanor exposure, may themselves contribute to heart rate lowering, and should be avoided [see Clinical Pharmacology ( 12.3 )] . Avoid use of Corlanor in patients with 2 nd degree atrioventricular block unless a functioning demand pacemaker is present [see Contraindications ( 4 ) ]. Pediatric Patients Bradycardia and first-degree heart block were observed in pediatric patients treated with Corlanor. Asymptomatic and symptomatic bradycardia were observed in 6.8% and 4.1% of pediatric patients treated with Corlanor, respectively. In the placebo treatment arm, 2.4% of pediatric patients had asymptomatic bradycardia, but none had symptomatic bradycardia. Bradycardia was managed through dose titration but did not result in study drug discontinuation [see Dosage and Administration ( 2.2 )] .
Side effects
6. ADVERSE REACTIONS Clinically significant adverse reactions that appear in other sections of the labeling include: Atrial Fibrillation [see Warnings and Precautions ( 5.2 )] Bradycardia and Conduction Disturbances [see Warnings and Precautions ( 5.3 )] Most common adverse reactions occurring in ≥ 1% of patients are bradycardia, hypertension, atrial fibrillation and luminous phenomena (phosphenes). ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Medical Information at 1-800-772-6436 (1-800-77-AMGEN) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adult Patients with Heart Failure In SHIFT, safety was evaluated in 3,260 patients treated with Corlanor and 3,278 patients given placebo. The median duration of Corlanor exposure was 21.5 months. The most common adverse drug reactions in the SHIFT trial are shown in Table 2 [see Warnings and Precautions ( 5.2 ) , ( 5.3 ) ] . Table 2. Adverse Drug Reactions with Rates ≥ 1.0% Higher on Ivabradine than Placebo occurring in > 1% on Ivabradine in SHIFT Ivabradine N = 3,260 Placebo N = 3,278 Bradycardia 10% 2.2% Hypertension, blood pressure increased 8.9% 7.8% Atrial fibrillation 8.3% 6.6% Phosphenes, visual brightness 2.8% 0.5% Luminous P henomena (Phosphenes) Phosphenes are phenomena described as a transiently enhanced brightness in a limited area of the visual field, halos, image decomposition (stroboscopic or kaleidoscopic effects), colored bright lights, or multiple images (retinal persistency). Phosphenes are usually triggered by sudden variations in light intensity. Corlanor can cause phosphenes, thought to be mediated through Corlanor’s effects on retinal photoreceptors [see Clinical Ph a rmacology ( 12.1 )] . Onset is generally within the first 2 months of treatment, after which they may occur repeatedly. Phosphenes were generally reported to be of mild to moderate intensity and led to treatment discontinuation in < 1% of patients; most resolved during or after treatment. Pediatric Patients with Heart Failure The safety of Corlanor in pediatric patients 6 months to less than 18 years of age is based on a clinical trial [see Clinical Studies ( 14.2 )] in symptomatic heart failure patients with dilated cardiomyopathy and elevated heart rate. This trial provides experience in 73 patients treated with Corlanor for a median duration of 397 days, and 42 patients given placebo. Bradycardia (symptomatic and asymptomatic) occurred at rates similar to those in adults. Phosphenes were observed in pediatric patients treated with Corlanor. 6.2 Postmarketing Experience Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or establish a causal relationship to drug exposure. The following adverse reactions have been identified in adults during post-approval use of Corlanor: syncope, hypotension, torsade de pointes, ventricular fibrillation, ventricular tachycardia, angioedema, erythema, rash, pruritus, urticaria, vertigo, and diplopia, and visual impairment.
Drug interactions
7. DRUG INTERACTIONS Avoid CYP3A4 inhibitors or inducers. ( 7.1 ) Negative chronotropes increase risk of bradycardia; monitor heart rate. ( 7.2 ) 7.1 Cytochrome P450-Based Interactions Corlanor is primarily metabolized by CYP3A4. Concomitant use of CYP3A4 inhibitors increases ivabradine plasma concentrations and use of CYP3A4 inducers decreases them. Increased plasma concentrations may exacerbate bradycardia and conduction disturbances. The concomitant use of strong CYP3A4 inhibitors is contraindicated [ s ee Contraindications ( 4 ) and Clinical Pharmacology ( 12.3 )] . Examples of strong CYP3A4 inhibitors include azole antifungals (e.g., itraconazole), macrolide antibiotics (e.g., clarithromycin, telithromycin), HIV protease inhibitors (e.g., nelfinavir), and nefazodone. Avoid concomitant use of moderate CYP3A4 inhibitors when using Corlanor. Examples of moderate CYP3A4 inhibitors include diltiazem, verapamil, and grapefruit juice [ s ee Warnings and Precautions ( 5.3 ) and Clinical Pharmacology ( 12.3 )] . Avoid concomitant use of CYP3A4 inducers when using Corlanor. Examples of CYP3A4 inducers include St. John’s wort, rifampicin, barbiturates, and phenytoin [ s ee Clinical Pharmacology ( 12.3 )] . 7.2 Negative Chronotropes Most patients receiving Corlanor will also be treated with a beta-blocker. The risk of bradycardia increases with concomitant administration of drugs that slow heart rate (e.g., digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking Corlanor with other negative chronotropes. 7.3 Pacemakers in Adults Corlanor dosing is based on heart rate reduction, targeting a heart rate of 50 to 60 beats per minute in adults [see Dos ag e and Administration ( 2.1 )] . Patients with demand pacemakers set to a rate ≥ 60 beats per minute cannot achieve a target heart rate < 60 beats per minute, and these patients were excluded from clinical trials [see Clinical Studies ( 14.1 )] . The use of Corlanor is not recommended in patients with demand pacemakers set to rates ≥ 60 beats per minute.
Use in specific populations
8. USE IN SPECIFIC POPULATIONS Lactation: Breastfeeding not recommended. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings in animals, Corlanor may cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of Corlanor in pregnant women to inform 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 (AUC 0-24hr ) at the MRHD resulted in embryo-fetal toxicity and teratogenicity manifested as abnormal shape of the heart, interventricular septal defect, and complex anomalies of primary arteries. Increased post-natal mortality was associated with these teratogenic effects in rats. In pregnant rabbits, increased post-implantation loss was noted at an exposure (AUC 0-24hr ) 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. Clinical Considerations Disease-associated Maternal and/or Embryo - fetal Risk Stroke volume and heart rate increase during pregnancy, increasing cardiac output, especially during the first trimester. Pregnant patients with left ventricular ejection fraction less than 35% on maximally tolerated doses of beta-blockers may be particularly heart rate dependent for augmenting cardiac output. Therefore, pregnant patients who are started on Corlanor, especially during the first trimester, should be followed closely for destabilization of their congestive heart failure that could result from heart rate slowing. Monitor pregnant women with chronic heart failure in 3 rd trimester of pregnancy for preterm birth. Data Animal Data In pregnant rats, oral administration of ivabradine during the period of organogenesis (gestation day 6-15) at doses of 2.3, 4.6, 9.3, or 19 mg/kg/day resulted in fetal toxicity and teratogenic effects. Increased intrauterine and post-natal mortality and cardiac malformations were observed at doses ≥ 2.3 mg/kg/day (equivalent to the human exposure at the MRHD based on AUC 0- 24 hr ). Teratogenic effects including interventricular septal defect and complex anomalies of major arteries were observed at doses ≥ 4.6 mg/kg/day (approximately 3 times the human exposure at the MRHD based on AUC 0- 24 hr ). In pregnant rabbits, oral administration of ivabradine during the period of organogenesis (gestation day 6-18) at doses of 7, 14, or 28 mg/kg/day resulted in fetal toxicity and teratogenicity. Treatment with all doses ≥ 7 mg/kg/day (equivalent to the human exposure at the MRHD based on AUC 0- 24 hr ) caused an increase in post-implantation loss. At the high dose of 28 mg/kg/day (approximately 15 times the human exposure at the MRHD based on AUC 0- 24 hr ), reduced fetal and placental weights were observed, and evidence of teratogenicity (ectrodactylia observed in 2 of 148 fetuses from 2 of 18 litters) was demonstrated. In the pre- and post-natal study, pregnant rats received oral administration of ivabradine at doses of 2.5, 7, or 20 mg/kg/day from gestation day 6 to lactation day 20. Increased post-natal mortality associated with cardiac teratogenic findings was observed in the F1 pups delivered by dams treated at the high dose (approximately 15 times the human exposure at the MRHD based on AUC 0- 24 hr ). 8.2 Lactation Risk Summary 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 [ s ee Data ] . Because of the potential risk to breastfed infants from exposure to Corlanor, breastfeeding is not recommended. Data Lactating rats received daily oral doses of [14C]-ivabradine (7 mg/kg) on post-parturition days 10 to 14; milk and maternal plasma were collected at 0.5 and 2.5 hours post-dose on day 14. The ratios of total radioactivity associated with [14C]-ivabradine or its metabolites in milk vs. plasma were 1.5 and 1.8, respectively, indicating that ivabradine is transferred to milk after oral administration. 8.3 Females and Males of Reproductive Potential Contraception Females Corlanor may cause fetal harm, based on animal data. Advise females of reproductive potential to use effective contraception during Corlanor treatment [ s ee Use in Specific Populations ( 8.1 )] . 8.4 Pediatric Use The safety and effectiveness of Corlanor 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 Corlanor in adult patients. The pediatric study included 116 patients in the following age groups: 17 patients in the 6 months to less than 12 months age group, 36 patients in the 1 year to less than 3 years age group, and 63 patients in the 3 years to less than 18 years age group [see Dosage and Administration ( 2.2 ), Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14.2 )] . The safety and efficacy of Corlanor have not been established in patients less than 6 months of age. Animal Data Ivabradine given orally to juvenile rats from post-natal day (PND) 7 until PND 77 at 7.5, 15 and 30 mg/kg/day did not affect post-natal (pre-weaning) development and reproductive performance (post-weaning development). Similar to adult animals, ivabradine decreased heart rate dose-dependently, and increased heart weights at the highest dose administered. Ivabradine also decreased white blood cell counts (lymphocytes) at the highest dose administered.
Pregnancy
8.1 Pregnancy Risk Summary Based on findings in animals, Corlanor may cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of Corlanor in pregnant women to inform 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 (AUC 0-24hr ) at the MRHD resulted in embryo-fetal toxicity and teratogenicity manifested as abnormal shape of the heart, interventricular septal defect, and complex anomalies of primary arteries. Increased post-natal mortality was associated with these teratogenic effects in rats. In pregnant rabbits, increased post-implantation loss was noted at an exposure (AUC 0-24hr ) 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. Clinical Considerations Disease-associated Maternal and/or Embryo - fetal Risk Stroke volume and heart rate increase during pregnancy, increasing cardiac output, especially during the first trimester. Pregnant patients with left ventricular ejection fraction less than 35% on maximally tolerated doses of beta-blockers may be particularly heart rate dependent for augmenting cardiac output. Therefore, pregnant patients who are started on Corlanor, especially during the first trimester, should be followed closely for destabilization of their congestive heart failure that could result from heart rate slowing. Monitor pregnant women with chronic heart failure in 3 rd trimester of pregnancy for preterm birth. Data Animal Data In pregnant rats, oral administration of ivabradine during the period of organogenesis (gestation day 6-15) at doses of 2.3, 4.6, 9.3, or 19 mg/kg/day resulted in fetal toxicity and teratogenic effects. Increased intrauterine and post-natal mortality and cardiac malformations were observed at doses ≥ 2.3 mg/kg/day (equivalent to the human exposure at the MRHD based on AUC 0- 24 hr ). Teratogenic effects including interventricular septal defect and complex anomalies of major arteries were observed at doses ≥ 4.6 mg/kg/day (approximately 3 times the human exposure at the MRHD based on AUC 0- 24 hr ). In pregnant rabbits, oral administration of ivabradine during the period of organogenesis (gestation day 6-18) at doses of 7, 14, or 28 mg/kg/day resulted in fetal toxicity and teratogenicity. Treatment with all doses ≥ 7 mg/kg/day (equivalent to the human exposure at the MRHD based on AUC 0- 24 hr ) caused an increase in post-implantation loss. At the high dose of 28 mg/kg/day (approximately 15 times the human exposure at the MRHD based on AUC 0- 24 hr ), reduced fetal and placental weights were observed, and evidence of teratogenicity (ectrodactylia observed in 2 of 148 fetuses from 2 of 18 litters) was demonstrated. In the pre- and post-natal study, pregnant rats received oral administration of ivabradine at doses of 2.5, 7, or 20 mg/kg/day from gestation day 6 to lactation day 20. Increased post-natal mortality associated with cardiac teratogenic findings was observed in the F1 pups delivered by dams treated at the high dose (approximately 15 times the human exposure at the MRHD based on AUC 0- 24 hr ).
Pediatric use
8.4 Pediatric Use The safety and effectiveness of Corlanor 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 Corlanor in adult patients. The pediatric study included 116 patients in the following age groups: 17 patients in the 6 months to less than 12 months age group, 36 patients in the 1 year to less than 3 years age group, and 63 patients in the 3 years to less than 18 years age group [see Dosage and Administration ( 2.2 ), Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14.2 )] . The safety and efficacy of Corlanor have not been established in patients less than 6 months of age. Animal Data Ivabradine given orally to juvenile rats from post-natal day (PND) 7 until PND 77 at 7.5, 15 and 30 mg/kg/day did not affect post-natal (pre-weaning) development and reproductive performance (post-weaning development). Similar to adult animals, ivabradine decreased heart rate dose-dependently, and increased heart weights at the highest dose administered. Ivabradine also decreased white blood cell counts (lymphocytes) at the highest dose administered. The decrease in white blood cell counts partially reversed within a 3-week recovery period. Exposures in male and female rats at the No Observed Adverse Effect Level (NOAEL) of 7.5 mg/kg/day, was approximately 3 and 8 times, respectively, steady state exposure associated with the highest received maintenance doses across age groups in pediatric patients (based on AUCs).
Geriatric use
8.5 Geriatric Use No pharmacokinetic differences have been observed in elderly (≥ 65 years) or very elderly (≥ 75 years) patients compared to the overall population. However, Corlanor has only been studied in a limited number of patients ≥ 75 years of age.
Overdosage
10. OVERDOSAGE 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.
Description
11. DESCRIPTION Corlanor (ivabradine) tablets and oral solution contains ivabradine as the active pharmaceutical ingredient. Ivabradine is a hyperpolarization-activated cyclic nucleotide-gated channel blocker that reduces the spontaneous pacemaker activity of the cardiac sinus node by selectively inhibiting the I f current, resulting in heart rate reduction with no effect on ventricular repolarization and no effects on myocardial contractility. The chemical name for ivabradine hydrochloride is 3-(3-{[((7 S )-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-2 H -3-benzazepin-2-one, hydrochloride. The molecular formula is C 27 H 36 N 2 O 5 ∙HCl, and the molecular weight (free base + HCl) is 505.1 (468.6 + 36.5). The chemical structure of ivabradine is shown in Figure 1. Figure 1 . Chemical Structure of Ivabradine Tablets Corlanor tablets are supplied in 5 mg and 7.5 mg tablets for oral administration. The tablets contain 5 mg and 7.5 mg of ivabradine, as the active ingredient, equivalent to 5.39 mg and 8.09 mg of ivabradine hydrochloride, respectively. The tablets contain the following inactive ingredients: colloidal silicon dioxide, glycerol, hypromellose, lactose monohydrate, magnesium stearate, maize starch, maltodextrin, polyethylene glycol 6000, red iron oxide, titanium dioxide, and yellow iron oxide. Oral Solution Corlanor 5 mg/5 mL (1 mg/mL) oral solution is formulated as a sterile, preservative-free, colorless solution for oral administration. Each 5 mL ampule contains 5 mg of ivabradine, equivalent to 5.39 mg ivabradine hydrochloride, as the active ingredient. The solution contains the following inactive ingredients: maltitol and water. Figure 1. Chemical Structure of Ivabradine
Mechanism of action
12.1 Mechanism of Action Corlanor blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker I f current, which regulates heart rate. In clinical electrophysiology studies, the cardiac effects were most pronounced in the sinoatrial (SA) node, but prolongation of the AH interval has occurred as has PR interval prolongation. There was no effect on ventricular repolarization and no effects on myocardial contractility [see Clinical Pharmacology ( 12.2 )] . Corlanor can also inhibit the retinal current I h . I h is involved in curtailing retinal responses to bright light stimuli. Under triggering circumstances (e.g., rapid changes in luminosity), partial inhibition of I h by Corlanor may underlie the luminous phenomena experienced by patients. Luminous phenomena (phosphenes) are described as a transient enhanced brightness in a limited area of the visual field [see A dverse R eactions ( 6.1 )] .
How supplied
16. HOW SUPPLIED/STORAGE AND HANDLING Tablets : Corlanor (ivabradine) 5 mg tablets are formulated as salmon-colored, oval-shaped, film-coated tablets functionally scored on both edges, marked with “5” on one face and bisected on the other face. They are supplied as follows: Bottles of 60 tablets with child-resistant closure (NDC 55513-800-60) Corlanor (ivabradine) 7.5 mg tablets are formulated as salmon-colored, triangular-shaped, film-coated tablets debossed with “7.5” on one face and plain on the other face. They are supplied as follows: Bottles of 60 tablets with child-resistant closure (NDC 55513-810-60) Oral Solution: Corlanor (ivabradine) oral solution is a colorless liquid supplied in an opaque, low density polyethylene (LDPE) plastic ampule. Each 5 mL ampule is individually packaged in a child-resistant foil pouch and supplied in cartons containing 28 foil pouches. Corlanor oral solution is supplied as 5 mg/5 mL (1 mg/mL) (NDC 55513-813-01). Storage Store Corlanor tablets and oral solution at 25°C (77°F); excursions permitted to 15°C - 30°C (59°F - 86°F) [see USP Controlled Room Temperature] . Protect Corlanor ampule from light by storing in the foil pouch until use.
Patient information
17. PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling [ see Medication Guide and Instructions for Use ] . Fetal Toxicity Advise pregnant women of the potential risks to a fetus. Advise females of reproductive potential to use effective contraception and to notify their healthcare provider with a known or suspected pregnancy [see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.1 ) , ( 8.3 )] . Low Heart Rate Advise patients to report significant decreases in heart rate or symptoms such as dizziness, fatigue, or hypotension [see Warnings and Precautions ( 5.3 )] . Atrial F ibrillation Advise patients to report symptoms of atrial fibrillation, such as heart palpitations or racing, chest pressure, or worsened shortness of breath [see Warnings and Precautions ( 5.2 )] . Phosphenes Advise patients about the possible occurrence of luminous phenomena (phosphenes). Advise patients to use caution if they are driving or using machines in situations where sudden changes in light intensity may occur, especially when driving at night. Advise patients that phosphenes may subside spontaneously during continued treatment with Corlanor [ see Adverse Reactions ( 6.1 )] . Drug Interactions Advise patients to avoid ingestion of grapefruit juice and St. John’s wort [ see Drug I nteractions ( 7.1 )] . Intake with Food Advise patients to take Corlanor twice daily with food [ see Dosage and Administration ( 2 )] . Oral Solution Advise parents/caregivers on preparation and administration instructions including the use of a calibrated oral syringe and a medicine cup (provided by the pharmacy) to avoid dosing errors [see Dosage and Administration ( 2.2 )] . Advise parents/caregivers that the oral solution should not be administered by the child. Advise parents/caregivers to not double up doses (e.g., if patient spits out the drug or caregiver forgets to give the drug at the prescribed time). Advise parents/caregivers to throw away the unused product remaining in the cup immediately after drawing up the prescribed dose in the syringe. Corlanor ® (ivabradine) Manufactured by : Amgen Inc. One Amgen Center Drive Thousand Oaks, California 91320-1799 Patent: http://pat.amgen.com/Corlanor/ © 2015, 2017, 2019, 2021 Amgen Inc. All rights reserved. [part number] v5
Label text from the FDA structured product label by Amgen Inc (revised Nov 10, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Ivabradine Hydrochloride in 3 products
Corlanor NDC products (3)
Corlanor recalls
- D-0612-2026 Jul 1, 2026 · Class II · Ongoing
Presence of Foreign Substance. - D-0615-2026 Jul 1, 2026 · Class II · Ongoing
Presence of Foreign Substance.
Frequently asked questions
What is Corlanor used for?
1. INDICATIONS AND USAGE Corlanor (ivabradine) is a hyperpolarization-activated cyclic nucleotide-gated channel blocker indicated: To reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure with reduced left ventricular ejection fraction. ( 1.1 ) For the treatment of stable symptomatic heart failure due to dilated…
What are the side effects of Corlanor?
6. ADVERSE REACTIONS Clinically significant adverse reactions that appear in other sections of the labeling include: Atrial Fibrillation [see Warnings and Precautions ( 5.2 )] Bradycardia and Conduction Disturbances [see Warnings and Precautions ( 5.3 )] Most common adverse reactions occurring in ≥ 1% of patients are bradycardia, hypertension, atrial fibrillation and luminous phenomena… See the full label for the complete list.
Who makes Corlanor?
Corlanor is listed by 1 labeler in the FDA NDC directory, including Amgen Inc.
Has Corlanor been recalled?
The FDA enforcement database lists 2 recalls for Corlanor, most recently D-0612-2026 (class ii): Presence of Foreign Substance.