AMIODARONE HCL

By | 2010-06-15

Chemistry

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.

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.

Pharmacology

Amiodarone’s mechanism of action is not fully understood, but it is believed that it possesses unique pharmacology from other antiarrhythmic agents. It can be best classified as a class III antiarrhythmic agent. Major properties include prolongation of myocardial cell-action potential duration and refractory period, and non-competitive alpha- and beta-adrenergic inhibition.

Uses – Indications

Because of its toxicity, amiodarone should only be considered for use in dogs with recurrent ventricular tachycardias that are not controlled with other therapies. As the risk of sudden death is high in Doberman pinschers exhibiting rapid, wide-complex ventricular tachycardia or syncope with recurrent VPC’s, amiodarone may be useful when other drug therapies are ineffective.

Pharmacokinetics

Amiodarone may be administered parenterally or orally. In humans, the oral absorption is slow and variable, with bioavailabilities ranging from 22-86%. 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 to 3.2 days.

Contraindications – Precautions – Reproductive Safety

Amiodarone is considered contraindicated in patients (people) hypersensitive to it; have severe sinus-node dysfunction with severe sinus bradycardia, 2nd or 3rd degree heart block or bradycardial syncope.

Clinical experience in veterinary patients is limited. Use only when other less toxic and more commonly used (and understood) drugs are ineffective.

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.

Adverse Effects – Warnings

Gastrointestinal effects (e.g., anorexia, vomiting) are apparently the most likely adverse effects seen in the limited number of canine patients treated. However, in people, adverse effects are very common while on amiodarone therapy. Those that most commonly cause discontinuation of the drug include: pulmonary infiltrates or pulmonary fibrosis (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.

Clinical experience in dogs is limited and the adverse effect profile of this drug in people warrants its use only when other less toxic agents are ineffective and treatment is deemed necessary.

Overdosage

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 betai agonists (e.g., isoproterenol); hypotension managed with positive inotropic agents or vasopressors. Neither amiodarone or its active metabolite are dialyzable.

Drug Interactions

There are several potentially significant interactions that may occur with amiodarone. The following is partial list of interactions that are most likely seen in veterinary patients: amiodarone may significantly increase the serum levels and/or pharmacologic effects of anticoagulants, beta blockers, calcium channel blockers (e.g. diltiazem, verapamil), cyclosporin, digoxin, lidocaine, methotrexate, procainamide, quinidine and theophylline. Cimetidine may increase the serum levels of amiodarone.

Drug/Lab Interactions

While most human patients remain euthyroid while receiving amiodarone, it may cause an increase in serum T4 and serum reverse T3 levels, and a reduction in serum T3 levels.

Doses

Doses for dogs:

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.

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.

Monitoring Parameters

1) Efficacy (ECG)

2) Toxicity (GI effects; liver enzymes; thyroid function tests; blood pressure; pulmonary radiographs if symptoms such as dyspnea/cough occur)

Client Information

Because of the “experimental” nature (relatively few canine patients have received this agent) and the toxicity dangers associated with its use, clients should give informed consent before the drug is prescribed.

Dosage Forms/Preparations/FDA Approval Status

Veterinary-Approved Products:

None

Human-Approved Products:

Amiodarone Oral Tablets 200 mg; Amiodarone Concentrate for Injection for IV Infusion 50 mg/ml in 3 ml ampules; Cordarone® (Wyeth-Ayerst); (Rx)