Ivabradine - Ivabradine tablet, Film Coated

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 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-blocker use.
  )

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.

• Lactation: Breastfeeding not recommended. (
  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

  [see Data]

  . Because of the potential risk to breastfed infants from exposure to ivabradine, 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.
  )

• Fetal toxicity: Females should use effective contraception. (
  5.1 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 (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)]

  .
  )
• Monitor patients for atrial fibrillation. (
  5.2 Atrial Fibrillation

  Ivabradine increases the risk of atrial fibrillation. In the Systolic Heart Failure Treatment with the I_fInhibitor 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.
  )
• Monitor heart rate decreases and bradycardia symptoms during treatment. (
  5.3 Bradycardia 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^stor 2^nddegree 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^nddegree atrioventricular block unless a functioning demand pacemaker is present

  [see Contraindications (4)]

  .
  )
• Not recommended in patients with 2^nd degree AV block. (
  5.3 Bradycardia 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^stor 2^nddegree 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^nddegree atrioventricular block unless a functioning demand pacemaker is present

  [see Contraindications (4)]

  .
  )