Amiodarone Hydrochloride

Antiarrhythmic Agent Class III Antiarrhythmic (also has Class I, II, and IV properties)

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO Loading: 10-15 mg/kg PO q12h for 7 days; Maintenance: 5-10 mg/kg PO q24h or divided q12h q12h for loading, then q24h or q12h for maintenance Duration: Long-term; adjust based on response and serum levels
Notes: Monitor ECG and serum levels (therapeutic range: 1-2.5 mcg/mL). Reduce dose if bradycardia or QT prolongation occurs.
Dog IV 5 mg/kg IV over 20-30 minutes (slow infusion), may repeat up to 15 mg/kg total As needed for emergency arrhythmias Duration: Acute management
Notes: Use with caution; monitor blood pressure and ECG continuously. Do not give rapid IV push.
Cat PO 10 mg/kg PO q12h for 7 days, then 5 mg/kg PO q24h q12h loading, then q24h Duration: Long-term
Notes: Cats are sensitive to amiodarone; monitor for hepatic and thyroid effects.
Horse PO Loading: 10 mg/kg PO q12h for 3 days, then 5 mg/kg PO q12h for 4 days, then 2.5 mg/kg PO q12h q12h Duration: Variable; often 2-4 weeks for atrial fibrillation
Notes: Monitor for GI upset and colic. Serum levels may be useful.
Horse IV 5 mg/kg IV over 30-60 minutes, diluted in saline Single dose or repeated as needed Duration: Acute arrhythmia management
Notes: Use with caution; may cause hypotension.
Cattle PO Not well established; extrapolated from other species: 10 mg/kg PO q12h q12h Duration: Limited data
Notes: Not approved for food animals; withdrawal times must be observed.
Small Ruminants PO Not established; use with caution N/A Duration: N/A
Notes: Limited data; not recommended.
Rabbit PO Not established; use with caution N/A Duration: N/A
Notes: Limited data; not recommended.
Bird/Poultry PO Not established N/A Duration: N/A
Notes: Limited data; not recommended.

Clinical Indications & Species Uses

General Indications
  • Management of life-threatening ventricular arrhythmias
  • Control of atrial fibrillation and supraventricular tachycardias
Dog (Canine)
  • Ventricular arrhythmias (e.g., ventricular tachycardia)
  • Atrial fibrillation
  • Supraventricular tachycardia
  • Life-threatening arrhythmias refractory to other agents
Cat (Feline)
  • Hypertrophic cardiomyopathy with arrhythmias
  • Ventricular arrhythmias
  • Atrial fibrillation (less common)
Horse (Equine)
  • Atrial fibrillation (especially chronic)
  • Ventricular arrhythmias
Cattle (Bovine)
  • May be used for refractory arrhythmias

Pharmacology & Mechanism of Action

Drug Class: Antiarrhythmic Agent | Pharmacological Group: Class III Antiarrhythmic (also has Class I, II, and IV properties)

Mechanism of Action: Amiodarone is a potent antiarrhythmic that prolongs the action potential duration and refractory period in cardiac tissues. It blocks sodium channels (Class I), beta-adrenergic receptors (Class II), potassium channels (Class III), and calcium channels (Class IV). It also has noncompetitive alpha-adrenergic blocking properties. These effects result in decreased automaticity, slowed conduction, and prolonged refractoriness, which suppress reentrant arrhythmias and ectopic foci.

Pharmacodynamics: Amiodarone exhibits complex pharmacodynamics with multiple electrophysiologic effects. It prolongs the QT interval, QRS duration, and PR interval. It decreases heart rate and myocardial contractility. It also has vasodilatory effects, reducing afterload and coronary vascular resistance. Its antiarrhythmic efficacy is sustained over time, with maximal effects seen after weeks of therapy due to tissue accumulation.

⚑ Pharmacokinetics Summary

Absorption: Oral absorption is slow and variable, with bioavailability ranging from 20-80% in humans; in dogs, oral bioavailability is approximately 50-60%. Peak plasma concentrations occur 3-7 hours after oral administration. Food increases absorption.
Distribution: Amiodarone is extensively distributed, with a large volume of distribution (Vd) due to high tissue binding, especially in adipose tissue, liver, lungs, and myocardium. It crosses the placenta and is excreted in milk. Protein binding is high (about 96%).
Metabolism: Amiodarone is extensively metabolized in the liver by cytochrome P450 enzymes (CYP3A4 and CYP2C8) to its active metabolite, desethylamiodarone (DEA). Both amiodarone and DEA accumulate in tissues and have long half-lives.
Excretion: Excretion is primarily via the biliary route into feces; renal excretion is minimal. The elimination half-life is long and variable: in dogs, it is approximately 2-4 weeks; in cats, it may be longer. Due to tissue accumulation, the drug persists in the body for months after discontinuation.
Half-Life: Dogs: 2-4 weeks; Cats: 2-4 weeks (estimated); Horses: 2-3 days (after IV); Humans: 40-55 days
Bioavailability: Oral: 20-80% (variable); in dogs, ~50-60%.
Protein Binding: Approximately 96% bound to plasma proteins (albumin and beta-lipoproteins).

Available Formulations & Strengths

Oral Tablet 100 mg, 200 mg, 400 mg (PO)
Injectable Solution 50 mg/mL (in 3 mL ampules) (IV)

Contraindications & Clinical Warnings

Contraindications:
  • Known hypersensitivity to amiodarone or iodine
  • Severe sinus node dysfunction (e.g., sick sinus syndrome) without a pacemaker
  • Second- or third-degree atrioventricular block without a pacemaker
  • Severe bradycardia
  • Cardiogenic shock
  • Thyroid dysfunction (hyper- or hypothyroidism) unless corrected
  • Pregnancy (unless benefits outweigh risks; may cause fetal harm)
Warnings & Clinical Precautions:
  • Use with caution in animals with hepatic disease, as amiodarone is hepatotoxic.
  • May cause pulmonary toxicity (pneumonitis, fibrosis) in dogs and cats; monitor respiratory signs.
  • May cause thyroid dysfunction (hyper- or hypothyroidism) due to high iodine content.
  • May cause corneal microdeposits in dogs; monitor ophthalmic exams.
  • May cause photosensitivity; avoid excessive sun exposure.
  • Use with caution in animals with electrolyte imbalances (hypokalemia, hypomagnesemia) as it may exacerbate arrhythmias.
  • May cause hypotension when given IV; monitor blood pressure.
  • May cause proarrhythmia (worsening of arrhythmias).
  • Use with caution in animals with heart failure; may worsen contractility.
  • In food animals, observe withdrawal times; not approved for use in food animals in many countries.

Adverse Effects & Reactions

Common:

  • Anorexia
  • Vomiting
  • Diarrhea
  • Lethargy
  • Bradycardia
  • Hypotension (IV)
  • Elevated liver enzymes

Serious / Severe:

  • Pulmonary fibrosis
  • Hepatotoxicity
  • Thyroid dysfunction (hyper/hypothyroidism)
  • Proarrhythmia (torsades de pointes)
  • Heart block
  • Congestive heart failure
  • Corneal microdeposits
  • Peripheral neuropathy

Rare:

  • Bone marrow suppression
  • Stevens-Johnson syndrome
  • Epididymitis
  • Alopecia
  • Cutaneous photosensitivity

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Digoxin Amiodarone increases digoxin concentrations by 70-100%; reduce digoxin dose by 50% and monitor levels. High
Beta-blockers (e.g., propranolol) Additive bradycardia and negative inotropic effects; use with caution. Moderate
Calcium channel blockers (e.g., diltiazem) Additive AV block and hypotension. Moderate
Warfarin Amiodarone inhibits CYP2C9, increasing warfarin levels and bleeding risk; reduce warfarin dose by 30-50%. High
Fluoroquinolones (e.g., enrofloxacin) Increased risk of QT prolongation and ventricular arrhythmias. Moderate
Macrolide antibiotics (e.g., erythromycin) Increased risk of QT prolongation. Moderate
Cimetidine Inhibits amiodarone metabolism, increasing levels. Moderate
Phenytoin Amiodarone inhibits phenytoin metabolism, increasing phenytoin levels. Moderate
Cyclosporine Amiodarone increases cyclosporine levels; monitor renal function. Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Severe bradycardia
  • Hypotension
  • AV block
  • Cardiac arrest
  • Nausea, vomiting
  • Lethargy
  • Tremors
  • Seizures (in severe cases)

Emergency Treatment Protocol: Treatment is symptomatic and supportive. There is no specific antidote. In acute overdose, consider gastric lavage if recent ingestion. Administer IV fluids for hypotension. Use atropine for bradycardia, and temporary cardiac pacing for AV block. Correct electrolyte imbalances. Monitor ECG continuously. For severe toxicity, consider hemodialysis (though not very effective due to high protein binding).

Food Animal Withdrawal Times

πŸ₯© Meat: 180 daysπŸ₯› Milk: 180 days

Amiodarone is not approved for use in food animals in the US. If used extra-label, a prolonged withdrawal time is recommended due to long half-life and tissue accumulation. Consult FARAD for specific recommendations.

Storage, Handling & Regulatory Information

Storage Temperature: Store at room temperature (20-25Β°C, 68-77Β°F). Protect from light and moisture.

Light Sensitivity: Light-sensitive β€” protect from direct exposure.

Handling & Special Conditions: Keep in tightly closed container. Do not freeze injectable solution.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use.

Extra-Label (Off-Label) Use: In the US, amiodarone is not FDA-approved for veterinary use; it is used extra-label under AMDUCA. For food animals, extra-label use is prohibited unless a valid VCPR and appropriate withdrawal times are established. In the EU, similar regulations apply.

Clinical Pearls & Practice Notes

πŸ’‘ Clinical Insights: Amiodarone is a potent antiarrhythmic used for refractory ventricular arrhythmias and atrial fibrillation in dogs, cats, and horses. Due to its long half-life and potential for toxicity, it is reserved for cases where other antiarrhythmics have failed. Therapeutic drug monitoring is recommended, with target serum levels of 1-2.5 mcg/mL for amiodarone and 0.5-1.5 mcg/mL for DEA. Baseline and periodic monitoring of liver enzymes, thyroid function, and chest radiographs (for pulmonary toxicity) are essential. In dogs, a loading dose is often used to achieve therapeutic levels quickly. In horses, amiodarone is effective for converting chronic atrial fibrillation, but it may cause GI side effects. Use with caution in animals with pre-existing hepatic or thyroid disease. Due to its iodine content, it can cause thyroid dysfunction. Always consider potential drug interactions, especially with digoxin and beta-blockers. For emergency IV use, slow infusion is critical to avoid hypotension. In food animals, amiodarone is not recommended due to prolonged withdrawal times.

References & Literature

  • πŸ“š Plumb's Veterinary Drug Handbook
  • πŸ“š Papich Veterinary Pharmacology and Therapeutics
  • πŸ“š Compendium of Veterinary Products (CVP)