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Therapeutic Classification:heart failure agents

Pharmacologic Classification: hyperpolarization-activated cyclic nucleotide-gated channel blockers

• To decrease the need for hospitalization due to worsening HF in patients with stable, but symptomatic chronic HF (ejection fraction <35%, sinus rhythm 70 bpm, receiving highest tolerated doses of beta-blockers or are unable to tolerate beta-blockers).
• Stable, symptomatic HF due to dilated cardiomyopathy in pediatric patients 6 mo old who are in sinus rhythm with an elevated heart rate.

• Inhibits the cardiac pacemaker I_f-current by acting as a hyperpolarization-activated cyclic nucleoside-gated channel blocker, resulting in ↓ spontaneous pacemaker activity of sinus node. Decreases heart rate without affecting contractility or ventricular repolarization.

• Lowering of heart rate with reduced need for hospitalization in patients with HF.

Absorption: 40% absorbed following oral administration (undergoes first pass metabolism); food delays absorption and ↑ blood levels.

Distribution: Unknown.

Metabolism/Excretion: Extensively metabolized, primarily by the CYP3A4 enzyme system. The major metabolite is pharmacologically active and has the same potency as ivabradine. Metabolites excreted equally in urine and feces; 4% excreted unchanged in urine.

Half-life: 6 hr.

(blood levels)

Contraindicated in:

• Acute decompensated heart failure
• Clinically significant hypotension
• Sick sinus syndrome, sinoatrial block, or 2nd or 3rd degree heart block (unless a functioning demand pacemaker is in place, ↑ risk of bradycardia)
• Clinically significant bradycardia
• Severe hepatic impairment
• Pacemaker dependence
• Concurrent use of strong CYP3A4 inhibitors
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Women of reproductive potential
• Pedi: Children <6 mo (safety and effectiveness not established).

CV: atrial fibrillation, bradycardia, heart block, hypertension, QT interval prolongation, sinus arrest, TORSADES DE POINTES.

EENT: phosphenes (luminous phenomena).

Drug-Drug:

• Strong CYP3A4 inhibitors, including azole antifungals, macolide anti-infectives, HIV protease inhibitors, and nefazodone may ↑ levels; concurrent use contraindicated.
• Moderate CYP3A4 inhibitors, including diltiazem and verapamil, may ↑ levels and ↑ risk of bradycardia; avoid concurrent use.
• CYP3A4 inducers, including barbiturates, phenytoin, and rifampicin may ↓ levels; avoid concurrent use.
• ↑risk of bradycardia with concurrent use of negative chronotropes including amiodarone, beta-blockers, and digoxin; monitor heart rate.
• Concurrent use of QT-interval prolonging drugs may ↑ risk of QT interval prolongation and torsades de pointes.

Drug-Natural Products:

• Concurrent use of St. John's wort may ↓ blood levels and effectiveness and should be avoided.

Drug-Food:

• Concurrent ingestion of grapefruit juice may ↑ blood levels and the risk of adverse effects and should be avoided.

• PO (Adults): 5 mg twice daily for 2 wk; dose may then be adjusted based on heart rate, not to exceed 7.5 mg twice daily; Patients with conduction defects or bradycardia: 2.5 mg twice daily initially.
• PO (Children 6 mo and 40 kg): Tablets: 2.5 mg twice daily; adjust dose at 2-wk intervals by 2.5 mg twice daily to achieve a heart rate reduction of 20%; not to exceed 7.5 mg twice daily.
• PO (Children 6 mo and <40 kg): Oral solution: 0.05 mg/kg twice daily; adjust dose at 2-wk intervals by 0.05 mg/kg twice daily to achieve a heart rate reduction of 20%; not to exceed 0.2 mg/kg twice daily (6 mo–<1 yr) or 0.3 mg/kg twice daily (1 yr) up to max of 7.5 mg twice daily.

(Generic available)

• Oral solution: 1 mg/mL;
• Tablets: 5 mg; 7.5 mg;

• Assess heart rate prior to, after 2 wk, and periodically during therapy. Adjust dose for a resting heart rate 50–60 bpm. If heart rate >60 bpm, increase dose by 2.5 mg given twice daily up to 7.5 mg twice daily. If heart rate 50–60 bpm, maintain dose. If heart rate <50 bpm or signs and symptoms of bradycardia (dizziness, fatigue, hypotension) occur, decrease dose by 2.5 mg given twice daily; if current dose is 2.5 mg given twice daily, discontinue ivabradine.
• Monitor ECG periodically during therapy. May cause atrial fibrillation and torsades de pointes. Discontinue ivabradine if atrial fibrillation occurs.

• PO: Administer twice daily with meals.
  • For oral solution, empty entire contents of ampule(s) into a medication cup. With a calibrated oral syringe, measure prescribed dose and administer orally. Discard unused oral solution; do not store or reuse. Solution is colorless.

• Instruct patient to take ivabradine as directed. If dose is missed or patient spits out drug omit dose; do not double doses.
• Advise patient to avoid taking grapefruit juice during therapy; may increase risk of side effects.
• Advise patient to notify health care professional if signs and symptoms of irregular or rapid heartbeat (heart pounding or racing, chest pressure, worsened shortness of breath, near fainting or fainting) or slower than normal heart rate (dizziness, fatigue, lack of energy) occur. In young children signs and symptoms of slow heart rate (poor feeding, difficulty breathing, turning blue).
• Inform patient that ivabradine may cause phosphenes or luminous phenomena, a transiently enhanced brightness in a limited area of the visual field, halos, image decomposition, colored bright lights, or multiple images. Phosphenes are usually triggered by sudden variations in light intensity. Usually begin within first 2 mo of therapy, may occur repeatedly of mild to moderate intensity, and resolve after therapy is discontinued.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other Rx, OTC, or herbal products, especially St. John's wort.
• May cause fetal harm. Advise females of reproductive potential to use effective contraception during therapy and to avoid breastfeeding during therapy. Advise patient to notify health care professional immediately if pregnancy is suspected.

• Lowering of heart rate to prevent hospitalization in patients with HF.

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