Amiodarone

Amiodarone is a multichannel antiarrhythmic classified principally as a class III agent. Veterinary use is reserved for severe or refractory arrhythmias in which the expected benefit justifies the potential for cardiac and systemic adverse effects. It has been used in dogs and horses for selected ventricular and supraventricular rhythm disturbances.

The drug is highly tissue-distributed and can accumulate with repeated administration, so its effects and interactions may continue after treatment changes. An investigational combination use in canine Chagas disease is separate from its established pharmacologic role in rhythm control.

Group

Class III antiarrhythmic

Mechanism of Action

Amiodarone chiefly inhibits outward cardiac potassium currents, slowing repolarization and prolonging the action potential and effective refractory period. By extending the period during which myocardium cannot be re-excited, it can interrupt re-entrant activity and suppress some tachyarrhythmias.

It also has sodium-channel, calcium-channel and alpha- and beta-adrenergic blocking actions. These additional effects can slow conduction, reduce automaticity and modify atrioventricular nodal behavior. The combined actions explain its usefulness across several rhythm disturbances as well as its potential to cause bradycardia, conduction abnormalities or hemodynamic deterioration.

Extensive tissue uptake and slow elimination contribute to delayed accumulation and persistent pharmacologic effects. Proposed antiparasitic actions in Chagas disease are distinct from its cardiac ion-channel effects and remain less well established.

Dose Rates

Dogs

Use / stage	Dose	Route	Schedule	Instructions
Ventricular arrhythmia — Loading	10–15 mg/kg	PO	Every 12 h	Up to 7 days; Continue with the intermediate-dose phase after 1 week.
Ventricular arrhythmia — Initial	5–7.5 mg/kg	PO	Every 12 h	Up to 14 days; Intermediate phase after loading; then use long-term maintenance.
Ventricular arrhythmia — Maintenance	7.5 mg/kg	PO	Every 24 h
Refractory arrhythmia - alternative course — Loading	25 mg/kg	PO	Every 12 h	Up to 4 days
Refractory arrhythmia - alternative course — Maintenance	25 mg/kg	PO	Every 24 h
Atrial fibrillation — Loading	15 mg/kg	PO		Up to 5 days; Loading for 5 days is described without an explicit repeat interval; do not infer it.
Atrial fibrillation — Maintenance	10 mg/kg	PO	Every 24 h
Breed-specific arrhythmia course — Loading	200 mg/animal	PO	Every 12 h	Up to 7 days; Described for Boxers and Dobermans; higher rates increased toxicity.
Breed-specific arrhythmia course — Maintenance	200 mg/animal	PO	Every 24 h	Described for Boxers and Dobermans.
Arrhythmia - IV treatment	5 mg/kg	IV	Once	Infuse over 10 minutes, subject to an initial rate limit of 30 mg/min; pretreat for vehicle-related reactions as indicated.
Chagas disease — Initial	15 mg/kg	PO	Every 12 h	Up to 7 days; Use with itraconazole; continue to the next phase.
Chagas disease — Maintenance	15 mg/kg	PO	Every 24 h	Up to 14 days; Second phase of the itraconazole combination course.
Chagas disease — Maintenance	7.5 mg/kg	PO	Every 24 h	Final phase with itraconazole; described for 12 months.
Atrial or ventricular arrhythmia - ambulatory alternative	8–10 mg/kg	PO	Every 12 h
Doberman ventricular arrhythmia course — Loading	10 mg/kg	PO	Every 12 h	Up to 7 days
Doberman ventricular arrhythmia course — Maintenance	8 mg/kg	PO	Every 24 h	Continue until 6 months, then reduce to 5 mg/kg daily.
Doberman ventricular arrhythmia course — Maintenance	5 mg/kg	PO	Every 24 h	After 6 months of the preceding phase. Severe ventricular tachycardia may initially require mexiletine 5–8 mg/kg PO every 8 hours for 1 week, followed by withdrawal once efficacy is confirmed.
Refractory ventricular tachycardia - twice-daily course — Loading	10 mg/kg	PO	Every 12 h	Up to 7 days
Refractory ventricular tachycardia - twice-daily course — Maintenance	5 mg/kg	PO	Every 12 h
Supraventricular or ventricular tachycardia - daily course — Loading	10–20 mg/kg	PO	Every 24 h	Up to 7 days; Loading lasts 5–7 days.
Supraventricular or ventricular tachycardia - daily course — Maintenance	5–10 mg/kg	PO	Every 24 h

Horses

Use / stage	Dose	Route	Schedule	Instructions
Atrial fibrillation or ventricular tachycardia — Loading	5 mg/kg/hour	IV	Continuous	Infuse for 1 hour, then reduce to the maintenance rate.
Atrial fibrillation or ventricular tachycardia — Maintenance	0.83 mg/kg/hour	IV	Continuous	Continue for the following 23 hours; oral absorption is unreliable.
Atrial fibrillation or ventricular tachycardia — Maintenance	1.9 mg/kg/hour	IV	Continuous	Optional extended phase for the following 30 hours after the initial 1-hour and 23-hour phases. Stop on rhythm conversion or adverse effects; prolonged infusions can cause hindlimb weakness and diarrhea.

Indications

Refractory or life-threatening ventricular arrhythmias, including recurrent hemodynamically unstable ventricular tachycardia.
Selected atrial fibrillation cases in dogs and horses requiring rhythm control.
Selected equine ventricular arrhythmias.
Reported combination treatment of canine Chagas disease with itraconazole; antiparasitic outcome evidence is limited.

Contraindications

Reserve for arrhythmias refractory to other treatment or substantial sudden-death risk.
Use cautiously with sinus-node dysfunction, advanced AV block, severe bradycardia or thyroid disease.
Pregnancy carries fetal thyroid and developmental risks.

Interactions

Beta blockers, calcium-channel blockers and digoxin may further slow conduction.
Do not mix IV solution with bicarbonate.
May increase warfarin, cyclosporine, lidocaine, phenytoin, procainamide, quinidine or methotrexate exposure.
QT-prolonging drugs, including some azoles, macrolides, fluoroquinolones, cisapride and ondansetron, can increase arrhythmia risk.
Cimetidine can increase amiodarone exposure; rifampin can reduce it.
General anesthetics and fentanyl can increase cardiovascular depression.

Adverse effects

Anorexia, vomiting and lethargy.
Bradycardia, AV block, hypotension, QT prolongation and heart failure.
Hepatotoxicity, thyroid dysfunction, pulmonary fibrosis, neutropenia and anemia.
Polysorbate-containing IV preparations may cause histamine-related pruritus, edema and vasodilation.

Toxicity

Overdose can cause hypotension, bradycardia, AV block, cardiogenic shock and hepatic injury. Treatment is supportive and may require pacing or vasoactive treatment. Amiodarone and its active metabolite are not dialyzable.

Preparations

Preparation	Form	Strength	Route
Amiodarone 100 mg tablet	Tablet	100 mg / tablet	PO
Amiodarone 200 mg tablet	Tablet	200 mg / tablet	PO
Amiodarone 400 mg tablet	Tablet	400 mg / tablet	PO
Amiodarone hydrochloride 50 mg/mL injection	Injection	50 mg / mL	IV
Nexterone 1.5 mg/mL Premixed IV formulation; distinguish vehicle and concentration from concentrated injection.	Injection	1.5 mg / mL	IV
Nexterone 1.8 mg/mL Premixed IV formulation; distinguish vehicle and concentration from concentrated injection.	Injection	1.8 mg / mL	IV

Monitoring and Administration

Monitor ECG during IV administration, CBC, liver indices and thyroid function during treatment. Plasma concentrations of 1–2.5 mcg/mL are described as therapeutic.

Give IV treatment slowly; the initial rate must not exceed 30 mg/min. Antihistamine pretreatment is described for vehicle-related reactions.

Keep tightly closed and protected from light at room temperature. Polysorbate-free formulations have different vehicle characteristics.

Use 5% dextrose for IV dilution. A 5 mg/mL suspension in equal Ora-Plus and Ora-Sweet or Ora-Sweet SF is stable for 91 days refrigerated at 5°C and protected from light. Monitor blood pressure and investigate pulmonary signs; a positive Coombs test may occur.