Ivabradine

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 ) 1.1 Heart 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-bloc …

• 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
• Adults The recommended starting dose of ivabradine tablets 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 ]
• 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 ]
• Table 1
• Dose Adjustment for Adults * [see Warnings and Precautions ] 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*

Tablets Ivabradine tablets 5 mg: Light salmon-colored, capsule-shaped, film-coated scored tablet debossed with "I5" divided by score on one side and plain on other side. The tablet is scored and can be divided into equal halves to provide a 2.5 mg dose. Ivabradine tablets 7.5 mg: Light salmon-colored, round-shaped, film-coated tablet debossed with "I" on one side & 7.5 on other side. …

The safety and efficacy of ivabradine tablets have not been established in patients less than 6 months of age.

No pharmacokinetic differences have been observed in elderly (≥ 65 years) or very elderly (≥ 75 years) patients compared to the overall population. However, ivabradine tablets has only been studied in a limited number of patients ≥ 75 years of age.

• Advise the patient to read the FDA-approved patient labelling [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 and Use in Specific Populations , ]. ● Low Heart Rate Advise patients to report significant decreases in heart rate or symptoms such as dizziness, fatigue, or hypotension [see Warnings and Precautions ] . …

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 o …

Avoid CYP3A4 inhibitors or inducers. ( 7.1 ) Negative chronotropes increase risk of bradycardia; monitor heart rate. ( 7.2 ) 7.1 Cytochrome 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) ]. …

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 Ivabradine tablets 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) ]. …

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 Ingenus Pharmaceuticals, LLC at 1-877-748-1970 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . …

8.1 Pregnancy Risk Summary Based on findings in animals, ivabradine tablets may cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of ivabradine tablets in pregnant women to inform any drug-associated risks. …

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.

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.