이바브라딘염산염

Ivabradine tablets are 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-blocker use.

Ivabradine 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 )

• 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 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) ] . 5.2 Atrial Fibrillation Ivabradine increases the risk of atrial fibrillation. In the Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial (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 [ see Clinical Studies (14) ] . Regularly monitor cardiac rhythm. Discontinue ivabradine if atrial fibrillation develops. 5.3 Bradycardia and Conduction Disturbances Adult Patients 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% …

8.1 Pregnancy 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 …