Amiodarone
Amiodarone
Generic Name
Amiodarone
Mechanism
- Class III activity: Potassium channel (IKr, IKs) blockade prolongs repolarization and the QT interval.
- Class I(a) and III effects: Sodium channel blockade slows conduction, especially in diseased myocardium.
- Class IV-like β‑blockade: Reduces automaticity and Ca²⁺ influx in the sinoatrial and atrioventricular nodes.
- Anti‑adrenergic properties: Decreases sympathetic tone, lowering catecholamine‑mediated arrhythmias.
- Result: Decreases the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) while maintaining atrial rhythm stability.
Pharmacokinetics
- Absorption: Oral bioavailability ~66%; food (especially high‑fat meals) increases absorption by ~70 %.
- Distribution: Highly lipophilic; extensive penetration into adipose tissue → volume of distribution ~600 L.
- Metabolism: Hepatic via CYP3A4 → desethyl‑amiodarone (active metabolite).
- Half‑life: Prolonged, 30–90 days (mean ~58 days).
- Elimination: ~70 % hepatic; ~30 % renal (creatinine clearance not a major determinant).
- Special populations: Pediatric dosing by weight; caution in hepatic or renal impairment due to slow clearance.
Indications
- Ventricular arrhythmias: Recurrent VT/VF, sustained monomorphic VT.
- Supraventricular arrhythmias: Atrial fibrillation/flutter, supraventricular tachycardia (SVT).
- Post‑operative or peri‑operative arrhythmias when other agents are ineffective.
- Bridging therapy to implantable cardioverter‑defibrillator (ICD) implantation or recovery.
- Heart failure with refractory arrhythmias where alternative agents fail.
Contraindications
- Contraindications:
- Hypersensitivity to amiodarone or iodine.
- Severe bradycardia or sick sinus syndrome (unless pacing available).
- Known QT‑prolongation syndrome (e.g., congenital Long QT).
- Warnings:
- Pulmonary toxicity: Fibrosis, interstitial pneumonitis.
- Hepatotoxicity: Elevated transaminases, cholestasis.
- Thyroid dysfunction: Hypo/hyperthyroidism due to iodine load and direct effects.
- Corneal deposits and visual impairment (e.g., optic neuropathy).
- QT prolongation & torsades de pointes.
- Drug interactions: Warfarin ↑ INR; digoxin ↓ levels; macrolides or fluoroquinolones ↑ risk of arrhythmia.
- Pregnancy: Category X; avoid.
- Children: Use only when benefits outweigh risks; weigh long‑term toxicity.
Dosing
| Form | Loading | Maintenance | Notes |
| Oral | 10‑15 mg/kg/day (~900 mg/day) ÷ 4–6×/day for 3–5 days | 1–2 mg/kg/day (~200 mg/day) | Increase gradually; monitor for hypotension |
| IV (Lipiodol) | 5–10 mg/kg over 1 h, then 3–5 mg/kg/h for 8–23 h | 0.5–1 mg/kg/h | Use slow infusion; monitor for chest pain/vasospasm |
• Transition: Oral maintenance typically starts 3–5 days after IV therapy.
• Max daily dose: 400 mg/day to minimize toxicity.
• Therapeutic drug monitoring (TDM) not routinely required but useful in non‑responsive cases.
Adverse Effects
Common:
• Gastro‑intestinal upset (nausea, dyspepsia)
• Headache, dizziness
• Blurred vision, dry eyes
• Hypotension (especially IV)
• Bradycardia
Serious:
• Pulmonary fibrosis → progressive dyspnea, cough
• Thyroid dysfunction (hypo/hyperthyroidism)
• Hepatic injury → jaundice, cholestasis
• QT‑c prolongation → torsades de pointes
• Corneal microdeposits → visual changes
• Venous thromboembolism (rare)
Monitoring
| Parameter | Frequency | Rationale |
| ECG (QTc) | Before initiation, after loading, then q‑weekly → monthly | Detect QT prolongation / torsades |
| Serum creatinine & LFTs | Baseline → q‑monthly | Hepatotoxicity & renal function |
| Thyroid panel (TSH, FT4) | Baseline → q‑3 months | Iodine‑load effect |
| Pulmonary function tests & chest X-ray | Baseline → q‑6 months | Early fibrosis detection |
| Ophthalmology exam | Baseline → q‑6 months | Corneal deposits/optic neuropathy |
| Blood pressure & pulse | At each dose change | Hypotension/bradycardia risk |
| INR (if on warfarin) | q‑2 weeks (after initiation) | Drug interaction |
| Plasma drug levels | Optional, in non‑responsive or toxicity scenarios | Verify therapeutic concentration |
Clinical Pearls
- Use as a bridge therapy: Amiodarone’s long half‑life allows safe transition from IV to oral, ideal for patients awaiting ICD implantation or cardiac surgery.
- Avoid rapid IV bolus: Infusions >1 mg/kg/h can trigger chest pain and ventricular ectopy; use a “slow dose” protocol (5 mg/h).
- Pulmonary toxicity risk is dose‑related: Limit cumulative IV dose to ≤1 mg/kg/day and monitor PFTs quarterly.
- Thyroid dysfunction may mimic cardiac failure: Routine TSH screening every 3 months is essential, as both hypo
- and hyperthyroid states can affect rhythm control.
- Corneal deposits rise after ~1 year: These are predominantly harmless but can impair night vision; routine ophthalmologic check is advised.
- Drug interactions: Amiodarone markedly increases warfarin’s INR; consider INR every 2 weeks for the first 6 months.
- Elderly & impaired hepatic function: Reduce maintenance dose and extend loading interval; watch for prolonged drug exposure leading to late toxicity.
- Contraindicated in persistent bradycardia: If the patient already has a heart rate <55 bpm, amiodarone can worsen conduction disturbances; pacing support is necessary.
- Pulmonary fibrosis onset is often subclinical: Look out for subtle dyspnea or reduced DLCO even before radiographic changes appear.
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• *This drug card is intended for educational purposes and is not a substitute for full prescribing information or professional judgment.*