Class III Antiarrhythmic
Highlights Of Prescribing Information
• Antidysrhythmic agent that can be used in dogs for arrhythmias associated with left ventricular dysfunction or to convert atrial fib into sinus rhythm; very limited experience warrants cautious use
• May be useful in horses to convert atrial fib or V tach into sinus rhythm
• Contraindicated in 2nd, 3rd degree heart block, bradyarrhythmias
• In DOGS: GI disturbances (vomiting, anorexia) most likely adverse effect, but neutropenia, thrombocytopenia, bradycardia, hepatotoxicity, positive Coombs’ test reported
• In HORSES: Limited use, accurate adverse effect profile to be determined; Hind limb weakness, increased bilirubin reported when used IV to convert atrial fib
• Many drug interactions
What Is Amiodarone HCL Used For?
Because of its potential toxicity and lack of experience with use in canine and equine patients, amiodarone is usually used when other less toxic or commonly used drugs are ineffective. It may be useful in dogs and horses to convert atrial fib into sinus rhythm and in dogs for arrhythmias associated with left ventricular dysfunction. In horses, one horse with Ventricular tachycardia was converted into sinus rhythm using amiodarone.
As the risk of sudden death is high in Doberman pinschers exhibiting rapid, wide-complex ventricular tachycardia or syncope with recurrent VPC’s, amiodarone maybe useful when other drug therapies are ineffective.
Amiodarone’s mechanism of action is not fully understood; it apparently is a potassium channel blocker that possesses unique pharmacology from other antiarrhythmic agents. It can be best classified a Class III antiarrhythmic agent that also blocks sodium and calcium channels, and beta-adrenergic receptors. Major properties include prolongation of myocardial cell action-potential duration and refractory period.
Amiodarone may be administered parenterally or orally. Amiodarone is widely distributed throughout the body and can accumulate in adipose tissue. Amiodarone is metabolized by the liver into the active metabolite desethylamiodarone. After oral administration of a single dose in normal dogs, amiodarone’s plasma half-life averaged 7.5 hours, but repeated dosing increased its half-life from 11 hours to 3.2 days.
In horses, amiodarone has a low oral bioavailability (range from 6-34%) and peak levels of amiodarone and desethylamiodarone occur about 7-8 hours after an oral dose. After IV administration amiodarone is rapidly distributed with a high apparent volume of distribution of 31 L/kg. In horses, amiodarone is relatively highly bound to plasma proteins (96%). Clearance was 0.35 L/kg/hr and median elimination half-lives for amiodarone and desethylamiodarone were approximately 51 and 75 hours, respectively ().
In humans, oral absorption is slow and variable, with bioavailabilities ranging from 22-86%. Elimination half-lives for amiodarone and desethylamiodarone range from 2.5-10 days after a single dose, but with chronic dosing, average 53 days and 60 days, respectively.
Before you take Amiodarone HCL
Contraindications / Precautions / Warnings
Amiodarone is considered contraindicated in patients (humans) hypersensitive to it, having severe sinus-node dysfunction with severe sinus bradycardia, 2nd or 3rd degree heart block, or bradycardial syncope.
Clinical experience in veterinary patients is limited. Consider use only when other less toxic and more commonly used drugs are ineffective.
Gastrointestinal effects (e.g., anorexia, vomiting) are apparently the most likely adverse effects seen in the limited number of canine patients treated. Hepatopathy (bilirubinemia, increased hepatic enzymes) has been reported in dogs on amiodarone. Because hepatic effects can occur before clinical signs are noted, routine serial evaluation of liver enzymes and bilirubin is recommended. Other adverse effects reported in dogs include bradycardia, neutropenia, thrombocytopenia, or positive Coombs’ test. During IV infusion, pain at injection site, and facial pruritus and hyperemia have been noted. Corneal deposits may be seen in dogs treated with amiodarone, but this affect apparently occurs less frequently in dogs than in humans.
In human patients, adverse effects are very common while on amiodarone therapy. Those that most commonly cause discontinuation of the drug include: pulmonary infiltrates or pulmonary fi-brosis (sometimes fatal), liver enzyme elevations, congestive heart failure, paroxysmal ventricular tachycardia, and thyroid dysfunction (hypo- or hyperthyroidism). An odd effect seen in some individuals is a bluish cast to their skin. Reversible corneal deposits are seen in a majority of humans treated with amiodarone.
Clinical experience in dogs is limited; the adverse effect profile of this drug in people warrants its use in veterinary patients only when other less toxic agents are ineffective and treatment is deemed necessary.
Reproductive / Nursing Safety
In laboratory animals, amiodarone has been embryotoxic at high doses and congenital thyroid abnormalities have been detected in offspring. Use during pregnancy only when the potential benefits outweigh the risks of the drug. In humans, the FDA categorizes this drug as category D for use during pregnancy (There is evidence of human fetal risk, hut the potential benefits from the use of the drug in pregnant women may he acceptable despite its potential risks.)
Overdosage / Acute Toxicity
Clinical overdosage experience is limited; most likely adverse effects seen are hypotension, bradycardia, cardiogenic shock, AV block, and hepatotoxicity. Treatment is supportive. Bradycardia may be managed with a pacemaker or beta-1 agonists (e.g., isoproterenol); hypotension managed with positive inotropic agents or vasopressors. Neither amiodarone nor its active metabolite are dialyzable.
How to use Amiodarone HCL
Note: Some human references state that because of the potential for drug interactions with previous drug therapies, the life-threatening nature of the arrhythmias being treated, and the unpredictability of response from amiodarone, the drug should be initially given (loaded) over several days in an inpatient setting where adequate monitoring can occur.
Amiodarone HCL dosage for dogs:
For conversion of atrial fibrillation:
a) At the time of writing (2007) one case report () and one retrospective evaluation () have been published using amiodarone to convert atrial fibrillation in dogs. Dosage recommendations are yet to be fully defined; monitor the current literature for further recommendations.
For recurrent ventricular tachycardia not controlled with other less toxic drugs:
a) 10-25 mg/kg PO twice daily for 7 days, followed by 5-7.5 mg/kg PO twice daily for 14 days, followed by 7.5 mg/kg PO once daily ()
b) For ventricular arrhythmias secondary to occult cardiomyopathy in Doberman pinschers: 10 mg/kg PO twice daily for one week and then 8 mg/kg PO once daily. For severe V-Tach, mexiletine is added at 5-8 mg/kg three times daily for one week. Once efficacy confirmed, patient weaned off mexiletine. ()
c) Amiodarone as above in “b”, but after 6 months may be reduced to 5 mg/kg once daily. ()
d) 10-20 mg/kg PO q12h ()
Amiodarone HCL dosage for horses:
For conversion of atrial fibrillation or ventricular tachycardia: a) 5 mg/kg/hr for one hour, followed by 0.83 mg/kg/hr for 23 hours and then 1.9 mg/kg/hour for the following 30 hours. In the study (A fib), infusion was discontinued when conversion occurred or when any side effects were noted. 4 of 6 horses converted from A fib; one horse from V tach. In order to increase success rate and decrease adverse effects, regimen should be further adapted based upon PK/PD studies in horses. ()
■ Efficacy (ECG)
■ Toxicity (GI effects; CBC, serial liver enzymes; thyroid function tests; blood pressure; pulmonary radiographs if clinical signs such as dyspnea/cough occur)
■ Because of the “experimental” nature (relatively few canine/equine patients have received this agent) and the toxicity dangers associated with its use, clients should give informed consent before the drug is prescribed.
Chemistry / Synonyms
An iodinated benzofuran, amiodarone is unique structurally and pharmacologically from other antiarrhythmic agents. It occurs as a white to cream colored lipophilic powder having a pKa of approximately 6.6. Amiodarone 200 mg tablets each contain approximately 75 mg of iodine.
Amiodarone HCL may also be known as: amiodaroni hydrochloridum, L-3428, 51087N, or SKF-33134-A; many trade names are available.
Storage / Stability/Compatibility
Tablets should be stored in tight containers, at room temperature and protected from light. A 3-year expiration date is assigned from the date of manufacture.
Injection should be stored at room temperature and protected from light or excessive heat. While administering, light protection is not necessary. Use D5W as the IV diluent. Amiodarone is reportedly compatible with dobutamine, lidocaine, potassium chloride, procainamide, propafenone, and verapamil. Variable compatibility is reported with furosemide and quinidine gluconate.
Dosage Forms / Regulatory Status
Veterinary-Labeled Products: None
The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information.
Amiodarone Oral Tablets: 100 mg, 200 mg & 400 mg; Cordarone (Wyeth-Ayerst); Pacerone (Upsher Smith); generic; (Rx)
Amiodarone Concentrate for Injection (for IV Infusion): 50 mg/mL in 3 mL amps & vials; Cordarone (Wyeth-Ayerst); generic; (Rx)