Ivabradine
Ivabradine
Generic Name
Ivabradine
Mechanism
Ivabradine blocks the hyperpolarisation‑activated “funny” current (I_f) in the sino‑atrial node.
• ↓ Spontaneous diastolic depolarisation → slower mean heart rate (35–50 % reduction).
• No direct effect on myocardial contractility or systemic vascular resistance.
• Reduced myocardial oxygen demand → symptomatic relief of angina and improved cardiac output in heart failure with reduced ejection fraction (HFrEF).
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Pharmacokinetics
| Parameter | Typical Value | Notes |
| Absorption | Oral, peak plasma level 1–2 h post‑dose | Reduced by food; 500 mg tablets taken on an empty stomach optimises bioavailability. |
| Bioavailability | ~20–30 % | Highly variable; food reduces by ≈50 %. |
| Metabolism | CYP3A4‑mediated → major role; minimal phase‑II conjugation | Strong CYP3A4 inhibitors (e.g., ketoconazole) ↑ plasma concentrations. |
| Half‑life | 7–17 h (dose‑dependent) | Allows twice‑daily dosing. |
| Elimination | 90 % renal, 10 % fecal | No dose adjustment required for mild–moderate hepatic impairment; caution in severe hepatic disease. |
| Drug Interactions | *CYP‑3A4 inhibitors/inducers, calcium channel blockers (verapamil), β‑blockers* | Avoid in combination with *verapamil* or *diltiazem*. |
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Indications
- Chronic stable angina (in sinus rhythm) when β‑blockers or calcium channel blockers are poorly tolerated or insufficient.
- Heart failure with reduced ejection fraction (HFrEF), NYHA class II–III, documented resting heart rate > 70 bpm despite optimal β‑blocker dosing.
- Combination with β‑blockers is permitted; synergistic heart‑rate reduction may be achieved.
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Contraindications
- Absolute Contraindications
- Sinus bradycardia (HR < 50 bpm)
- Second‑ or third‑degree AV block (unless a pacemaker is present)
- Atrial fibrillation or flutter (does not reduce atrial rate)
- Ventricular arrhythmias (paroxysmal)
- Warnings
- Liver disease – may increase drug exposure; use cautiously.
- Drug interactions – avoid co‑administration with strong CYP3A4 inhibitors/inducers and verapamil/diltiazem.
- Pregnancy & lactation – category C; avoid unless benefits outweigh risks.
- Ophthalmologic – evaluate baseline visual acuity; advise patients about transient visual disturbances.
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Dosing
1. Initiate: 5 mg PO twice daily (total 10 mg/day)
2. Titrate:
• If resting heart rate > 70 bpm and tolerated → add 2.5 mg BID → 7.5 mg BID (15 mg/day).
• Maximum permitted dose: 15 mg/day (7.5 mg BID).
3. Timing: Take with or without food, but avoid co‑administration with high‑fat meals.
4. When to withhold: Due to bradycardia, significant AV block, or visual disturbances.
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Adverse Effects
| Common | Serious | Notes |
| Visual disturbances (phosphenes, colour‑saturation changes) | Severe bradycardia / AV block | Symptoms often transient; counsel patients. |
| Headache | Hypotension (rare) | Monitor blood pressure with β‑blockers. |
| Nausea, dizziness | QT prolongation (rare; drug‑induced) | Baseline ECG recommended. |
| Tachycardia (paradoxical) | Serious arrhythmias | Occurs in patients with underlying conduction disease. |
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Monitoring
- Baseline
- Resting heart rate & rhythm (sinus).
- ECG (to rule out conduction disease).
- Liver function tests (ALT, AST).
- Visual acuity test (if ocular disease suspected).
- Ongoing
- Resting heart rate 1 week post‑initiation, then monthly.
- ECG 3 months after achievement of target dose.
- LFTs every 3 months in long‑term therapy.
- Kidney function (if severe renal impairment).
- Patient‑reported
- Any visual changes, dizziness, syncope, palpitations, or unusual fatigue.
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Clinical Pearls
- “If” I‑f: Remember that ivermabride only slows sino‑atrial node firing; it does not affect atrial or ventricular conduction.
- Combination therapy: Use with caution in patients already on β‑blockers; monitor for additive bradycardia.
- Food Fact: A 500‑mg capsule taken in the morning on an empty stomach has optimal absorption; skip a meal for at least 30 min.
- Drug Interactions Hack: *CYP3A4 inhibitors* → ↑ 50 % risk; *CYP3A4 inducers* → ↓ 40 % efficacy.
- Bradycardia Alert: If HR drops below 50 bpm within 48 h of dose increase, consider dose reduction or discontinuation.
- Pregnancy Check: Although limited data, patients of childbearing potential should use effective contraception; counsel regarding possible teratogenic risk.
- Visual Symptom Management: Pre‑timed visual checks and patient education can reduce anxiety and discontinuation rates.
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