heart failure agents
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).
Inhibits the cardiac pacemaker If -current by acting as a hyperpolarization-activated cyclic nucleoside-gated channel blocker, resulting in ↓ spontaneous pacemaker activity of sinus node. Decreases heart rate without effecting contractility or ventricular repolarization.
Lowering of heart rate with reduced need for hospitalization in HF patients.
Absorption: 40% absorbed following oral administration (undergoes first pass metabolism); food delays absorption and ↑ blood levels.
Metabolism and 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.
TIME/ACTION PROFILE (blood levels)
|PO||unknown||1 hr||12 hr|
- Acute decompensated heart failure;
- BP <90/50 mmHg;
- Sick sinus syndrome, sinoatrial block or 2nd or 3rd degree heart block (unless a functioning demand pacemaker is in place, ↑ risk of bradycardia);
- Resting heart rate <60 bpm (before treatment);
- Severe hepatic impairment;
- Concurrent use of demand pacemaker set at ≥60 bpm;
- Pacemaker dependence;
- Concurrent use of strong CYP3A4 inhibitors;
- OB: Pregnancy (may cause fetal harm);
- Lactation:Discontinue ivabradine or discontinue breast feeding.
Use Cautiously in:
- Female patients with reproductive potential (effective contraception required);
- Pedi: Safety and effectiveness not established.
Adverse Reactions/Side Effects
EENT: phosphenes (luminous phenomena)
CV: TORSADE DE POINTES, atrial fibrillation, bradycardia, heart block, hypertension, QT interval prolongation, sinus arrest
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- 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 torsade de pointes.
Concurrent use of St. John's wort may ↓ blood levels and effectiveness and should be avoided.
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 two weeks, 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.
Tablets: 5 mg, 7.5 mg
- Assess heart rate prior to, after 2 wks, 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 torsade de pointes. Discontinue ivabradine if atrial fibrillation occurs.
- Decreased cardiac output (Indications)
- PO: Administer twice daily with meals.
- Instruct patient to take ivabradine as directed.
- Advise patient to avoid taking grapefruit juice during therapy; may increase risk of side effects.
- 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 be teratogenic. Advise female patient to use effective contraception during therapy and to notify health care professional if pregnancy is planned or suspected and to avoid breast feeding.
Lowering of heart rate to prevent hospitalization in patients with HF.
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