Ivabradine 5 mg Tablet, Film Coated, 180-count
Other active recalls for Ivabradine (different manufacturers) — 2 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Hyperpolarization-activated Cyclic Nucleotide-gated Channel Blocker class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Ivabradine is used to treat certain adults with heart failure (condition in which the heart is unable to pump enough blood to the other parts of the body) to decrease the risk that their condition will worsen and need to be treated in a hospital. It is also used to treat a certain type of heart failure in children 6 months of age and older due to cardiomyopathy (a condition in which the heart muscle becomes weakened and enlarged). Ivabradine is in a class of medications called hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers. It works by slowing the heart rate so the...
Read the full MedlinePlus article ↗- Ivabradine slows your heart rate by acting directly on your heart's natural pacemaker. When your heart is beating too fast, it has to work harder, which can worsen heart failure sy...
- What exactly is ivabradine supposed to do for my heart failure?
- Yes, it does matter. You should take ivabradine with food every time. Food increases the amount of the drug your body absorbs, which is actually part of how the standard dose is de...
- Those brief flashes or areas of extra brightness are called phosphenes, and they're a known side effect of ivabradine. The drug affects a channel in the eye's retina that is simila...
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII 3SY5LH9PMK
Anhydrous lactose is a milk sugar with no water content. It acts as a filler and binder in tablets and capsules, adding bulk and helping ingredients stick together.
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UNII REK4960K2U
Butylated hydroxyanisole is a synthetic preservative that prevents oils and fats in medicines from spoiling or becoming rancid. It keeps the medicine stable and extends its shelf life.
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BHT is a synthetic antioxidant that prevents fats and oils in medicines from breaking down and becoming rancid. It helps keep the product stable and effective during storage.
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UNII 1K09F3G675
Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
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UNII EX438O2MRT
Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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UNII RFW2ET671P
Hydroxypropyl cellulose is a plant-derived thickening agent made from cellulose. It acts as a binder to hold tablet ingredients together and as a film-former to coat tablets or control how fast the medicine releases.
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Hypromellose 2910 is a plant-based cellulose derivative that acts as a thickener, binder, and film-coating agent. It helps control how quickly the medicine dissolves and protects the tablet or capsule from moisture and light.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII 7CVR7L4A2D
A starch-derived carbohydrate produced by breaking down corn, potato, or tapioca starch. It functions as a filler and binder to give the medicine bulk and texture, and sometimes as a mild sweetener or texture enhancer in powders and tablets.
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UNII 30IQX730WE
Polyethylene glycol 6000 is a synthetic polymer made from ethylene glycol units. It acts as a binder, filler, and solubilizer in medicines to help hold ingredients together, add bulk, and improve how well active drugs dissolve and absorb.
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UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
12 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $3.27 | $588.33 / 180 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Ivabradine 5 mg 31722-0053-60 | Camber | 60 tablets | $0.764 | AB | Availability likely | — |
| Ivabradine 5 mg 50742-0362-60 | Ingenus | 60 tablets | $0.764 | AB | Availability likely | — |
| Ivabradine 5 mg 60687-0862-21 | American | 1 tablet | $0.764 | AB | Availability likely | — |
| ivabradine 5 mg 69452-0190-17 | Bionpharma | 60 tablets | $0.764 | AB | Availability likely | — |
| ivabradine 5 mg 70710-1471-06 | Zydus | 60 tablets | $0.764 | AB | Availability likely | — |
| Ivabradine 5 mg 72603-0934-01 | Northstar | 60 tablets | $0.764 | AB | Availability likely | — |
| Corlanor 5 mg 55513-0800-60 | Amgen | 60 tablets | $10.009 | — | Availability likely | — |
| Ivabradine 5 mgthis 46708-0679-45 | Alembic | 180 tablets | — | AB | FDA listed | — |
| Ivabradine 5 mg 51407-0592-60 | Golden | 60 tablets | — | AB | FDA listed | — |
| Ivabradine 5 mg 62332-0679-45 | Alembic | 180 tablets | — | AB | FDA listed | — |
| ivabradine 5 mg 70771-1863-06 | Zydus | 60 tablets | — | AB | FDA listed | — |
| Ivabradine 5 mg 72205-0336-18 | Novadoz | 180 tablets | — | AB | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 46708-0679-45 You're viewing this | 180 TABLET, FILM COATED in 1 BOTTLE (46708-679-45) | 2024-12-20 | Active |
| 46708-0679-60 | 60 TABLET, FILM COATED in 1 BOTTLE (46708-679-60) | 2024-12-20 | Active |
You're viewing the largest of 2 pack sizes for this product.
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🧭 About this NDC listing & data coverage
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Ivabradine tablets are 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 )
1.1Heart Failure in Adult Patients Ivabradine tablets are 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.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Adult patients • Starting dose is 2.5 (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 )
2.1Adults The recommended starting dose of ivabradine tablet 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, ivabradine 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 to 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)]
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Ivabradine tablets 5 mg having functional scoring are light salmon to salmon-colored, oval-shaped, film-coated tablets scored on both edges, debossed with ‘A’, score and ‘7’ on one face and plain on the other face. Ivabradine tablets 7.5 mg are light salmon to salmon-colored, triangular-shaped, film-coated tablets debossed with ‘662’ on one face and ‘L’ on the other face. • Tablets: 5 mg (having functional scoring), 7.5 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Ivabradine tablets are 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 Cautions ▾
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 )
5.1Fetal 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 (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 ivabradine [see Use in Specific Populations (8.3)] .
5.2Atrial Fibrillation Ivabradine 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% per patient-year in patients treated with ivabradine and 3.9% per patient-year in patients treated with placebo [see Clinical Studies (14)] . Regularly monitor cardiac rhythm. Discontinue ivabradine if atrial fibrillation develops.
5.3Bradycardia and Conduction Disturbances Adult Patients Bradycardia, sinus arrest, and heart block have occurred with ivabradine. The rate of bradycardia was 6% 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., 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 ivabradine exposure, may themselves contribute to heart rate lowering, and should be avoided [see Clinical Pharmacology (12.3)] . Avoid use of ivabradine in patients with 2 nd degree atrioventricular block unless a functioning demand pacemaker is present [see Contraindications (4)] .
🤒 Adverse Reactions ▾
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 FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical 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 ivabradine and 3,278 patients given placebo. The median duration of ivabradine 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% 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 Phenomena (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. Ivabradine can cause phosphenes, thought to be mediated through ivabradine’s effects on retinal photoreceptors [see Clinical Pharmacology (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.
6.2Postmarketing 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 ivabradine: 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 )
7.1Cytochrome P450-Based Interactions Ivabradine 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 [see 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 ivabradine.
Examples of moderate CYP3A4 inhibitors include diltiazem, verapamil, and grapefruit juice [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)] . Avoid concomitant use of CYP3A4 inducers when using ivabradine. Examples of CYP3A4 inducers include St.
John’s wort, rifampicin, barbiturates, and phenytoin [see Clinical Pharmacology (12.3)] .
7.2Negative Chronotropes Most patients receiving ivabradine 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 ivabradine with other negative chronotropes.
7.3Pacemakers in Adults Ivabradine dosing is based on heart rate reduction, targeting a heart rate of 50 to 60 beats per minute in adults [see Dosage 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 ivabradine 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 )
8.1Pregnancy Risk Summary 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 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 ivabradine, 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 to 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 0-24hr ).
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 0-24hr ). In pregnant rabbits, oral administration of ivabradine during the period of organogenesis (gestation day 6 to 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 0-24hr ) 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 0-24hr ), 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 0-24hr ).
8.2Lactation 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 [see Data] . Because of the potential risk to breastfed infants from exposure to ivabradine,…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary 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 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 ivabradine, 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 to 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 0-24hr ).
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 0-24hr ). In pregnant rabbits, oral administration of ivabradine during the period of organogenesis (gestation day 6 to 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 0-24hr ) 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 0-24hr ), 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 0-24hr ).
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and efficacy of ivabradine have not been established in patients less than 6 months of age.
🧓 Geriatric Use ▾
8.5Geriatric 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.
🆘 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Ivabradine 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)] .
Ivabradine 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 ivabradine 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 Adverse Reactions (6.1)] .
12.2Pharmacodynamics 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 patients with higher baseline heart rate). At recommended doses, 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 patients with preexisting conduction system disease (first-or second-degree AV block or left or right bundle branch block) requiring electrophysiologic study, IV ivabradine (0.2 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.
12.3Pharmacokinetics The peak concentration (C max ) and area under the plasma concentration time curve (AUC) are similar for ivabradine and S 18982 between oral solution and tablets for the same dose. Absorption and Bioavailability 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.
Food delays absorption by approximately 1 hour and increases plasma exposure by 20% to 40%. Ivabradine should be taken with food [see Dosage and Administration (2)] . Ivabradine is approximately 70% plasma protein bound, and the volume of distribution at steady state is approximately 100 L.
Metabolism and Excretion The pharmacokinetics of ivabradine are linear over an oral dose range of 0.5 mg to 24 mg. 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
4.2L/h, with ~ 4% of an oral dose excreted unchanged in urine. The excretion of metabolites occurs to a similar extent via feces and urine. Drug Interactions The effects of coadministered drugs (CYP3A4 inhibitors, substrates, inducers, and other concomitantly administered drugs) on the pharmacokinetics of ivabradine were studied in several single-and multiple-dose studies.
Pharmacokinetic measures indicating the magnitude of these interactions are presented in Figure 2. Figure 2. Impact of Coadministered Drugs on the Pharmacokinetics of Ivabradine Digoxin exposure did not change when concomitantly administered with…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Ivabradine 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)] .
Ivabradine 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 ivabradine 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 Adverse Reactions (6.1)] .
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Ivabradine tablets 5 mg having functional scoring are light salmon to salmon-colored, oval-shaped, film-coated tablets scored on both edges, debossed with ‘A’, score and ‘7’ on one face and plain on the other face. They are supplied as follows: Bottle of 60 tablets with child resistant closure, NDC 46708-679-60 Bottle of 180 tablets with child resistant closure, NDC 46708-679-45 Ivabradine tablets 7.5 mg are light salmon to salmon-colored, triangular-shaped, film-coated tablets debossed with ‘662’ on one face and ‘L’ on the other face.
They are supplied as follows: Bottle of 60 tablets with child resistant closure, NDC 46708-680-60 Bottle of 180 tablets with child resistant closure, NDC 46708-680-45 Storage Store ivabradine tablets at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
📋 Description ▾
11 DESCRIPTION Ivabradine tablets contain 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-{[((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 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 Ivabradine tablets are formulated as light salmon to salmon colored, film-coated tablets for oral administration in strengths of 5 mg and 7.5 mg of ivabradine, equivalent to 5.39 mg and 8.09 mg of ivabradine hydrochloride respectively. The tablets contain the following inactive ingredients: maltodextrin, lactose anhydrous, butylated hydroxyanisole, butylated hydroxytoluene, hypromellose 2910, colloidal silicon dioxide, magnesium stearate, hydroxypropyl cellulose, titanium dioxide, polyethylene glycol 6000, iron oxide yellow and iron oxide red. ivabradine-structure.jpg
💬 Information for Patients ▾
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 Fibrillation 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 ivabradine tablets [see Adverse Reactions (6.1)]. Drug Interactions Advise patients to avoid ingestion of grapefruit juice and St.
John’s wort [see Drug Interactions (7.1)]. Intake with Food Advise patients to take ivabradine tablets twice daily with food [see Dosage and Administration (2)]. Manufactured by: Alembic Pharmaceuticals Limited (Formulation Division), Village Panelav, P.
O. Tajpura, Near Baska, Taluka-Halol, Panchmahal, Gujarat, India. Revised: 09/2024
💬 Medication Guide ▾
MEDICATION GUIDE Ivabradine ( eye-VAB-ra-deen ) Tablets What is the most important information I should know about ivabradine tablets? Ivabradine tablets may cause serious side effects in adults, including: • Harm to an unborn baby . Females who are able to get pregnant: o Must use effective birth control during treatment with ivabradine tablets. o Tell your doctor right away if you become pregnant during treatment with ivabradine. • Increased risk of irregular or rapid heartbeat (atrial fibrillation or heart rhythm problems) .
Tell your doctor if you feel any of the following symptoms of an irregular or rapid heartbeat: o heart is pounding or racing (palpitations). o chest pressure. o worsened shortness of breath. o near fainting or fainting. • Slower than normal heart rate (bradycardia) . Tell your doctor if you have: o a slowing of heart rate, or o symptoms of a slow heart rate such as dizziness, fatigue, lack of energy. In young children signs and symptoms of slow heart rate may include: poor feeding, difficulty breathing or turning blue.
What are ivabradine tablets? Ivabradine tablets are prescription medicine used: • to treat adults who have chronic (lasting a long time) heart failure, with symptoms, to reduce their risk of hospitalization for worsening heart failure. Who should not take ivabradine tablets?
Do not take ivabradine tablets if you have: • symptoms of heart failure that recently worsened • very low blood pressure (hypotension) • certain heart conditions: sick sinus syndrome, sinoatrial block, or 3 rd degree atrioventricular block • a slow resting heart rate before treatment with ivabradine tablets. Ask your doctor what a slow resting heart rate is for you. • certain liver problems • been prescribed any medicines that can increase the effects of ivabradine tablets. Ask your doctor if you are not sure if you have any of the medical conditions listed above.
What should I tell my doctor before taking ivabradine tablets? Before you take ivabradine tablets, tell your doctor about all of your medical conditions, including if you: • have any other heart problems, including heart rhythm problems, a slow heart rate, or a heart conduction problem. • are breastfeeding or planning to breastfeed. It is not known if ivabradine passes into breast milk.
You and your doctor should decide if you will take ivabradine tablets or breastfeed; do not do both. • are pregnant or planning to become pregnant. See “What is the most important information I should know about ivabradine tablets? -Harm to an unborn baby” section. Tell your doctor about all the medicines you take, including prescription and over the counter medicines, vitamins, and herbal supplements.
Ivabradine tablets may affect the way other medicines work, and other medicines may affect how ivabradine tablets works. This could cause serious side effects. How should you take ivabradine tablets? • Take ivabradine tablets exactly as your doctor tells you. • Do not stop taking ivabradine tablets without talking with your doctor. • Ivabradine comes as a tablet. o Tell your doctor if you have trouble swallowing tablets. o Your doctor may change your dose of ivabradine tablets during treatment • Take ivabradine tablets 2 times each day with food. • If you miss a dose of ivabradine tablets, do not give another dose.
Give the next dose at the usual time. • If you take too much ivabradine tablets, call your doctor or go to the nearest emergency room right away. What should you avoid while taking ivabradine tablets? • Avoid drinking grapefruit juice and taking St. John’s wort during treatment with ivabradine tablets.
These can affect the way ivabradine tablets works and may cause serious side effects. What are the possible side effects of ivabradine tablets? Ivabradine tablets may cause serious side effects.
See “What is the most important information I should know about ivabradine tablets?” The most common side effects of ivabradine tablets are: • increased blood pressure • tempor…