Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.

AMIODARONE HCL

Chemistry - An iodinated benzofuran, amiodarone is unique structurally and pharmacologicallyfrom other antiarrhythmic agents. It occurs as a white to cream colored lipophilic powder having apKa of approximately 6.6. Amiodarone 200 mg tablets each contain approximately 75 mg ofiodine.

Storage, Stability, Compatibility

Tablets should be stored in tight containers, at room tempera- ture and protected from light. A 3 year expiration date is assigned from the date of manufacture.

Pharmacology - AMIODARONE HCL

Amiodarone's mechanism of action is not fully understood, but it is believed thatit possesses unique pharmacology from other antiarrhythmic agents. It can be best classified as aclass III antiarrhythmic agent. Major properties include prolongation of myocardial cell-actionpotential 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 dogswith recurrent ventricular tachycardias that are not controlled with other therapies. As the risk ofsudden death is high in Doberman pinschers exhibiting rapid, wide-complex ventricular tachycardiaor syncope with recurrent VPC's, amiodarone may be useful when other drug therapies areineffective.

Pharmacokinetics - AMIODARONE HCL

Amiodarone may be administered parenterally or orally. In humans, the oralabsorption is slow and variable, with bioavailabilities ranging from 22-86%. Amiodarone is widelydistributed throughout the body and can accumulate in adipose tissue. Amiodarone is metabolizedby the liver into the active metabolite desethylamiodarone. After oral administration of a single dosein normal dogs, amiodarone's plasma half-life averaged 7.5 hours, but repeated dosing increased itshalf-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 sinusbradycardia, 2nd or 3rd degree heart block or bradycardial syncope.
Clinical experience in veterinary patients is limited. Use only when other less toxic and morecommonly used (and understood) drugs are ineffective.
In laboratory animals, amiodarone has been embryotoxic at high doses and congenital thyroidabnormalities have been detected in offspring. Use during pregnancy only when the potentialbenefits outweigh the risks of the drug.

Adverse Effects, Warnings

Gastrointestinal effects (e.g., anorexia, vomiting) are apparently themost 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 causediscontinuation of the drug include: pulmonary infiltrates or pulmonary fibrosis (sometimes fatal), liver enzyme elevations, congestive heart failure, paroxysmal ventricular tachycardia and thyroiddysfunction (hypo- or hyperthyroidism). An odd effect seen in some individuals is a bluish cast totheir skin.
Clinical experience in dogs is limited and the adverse effect profile of this drug in people warrantsits 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 beta1 agonists (e.g., isoproterenol); hypotensionmanaged with positive inotropic agents or vasopressors. Neither amiodarone or its active metaboliteare dialyzable.
Drug/

Drug Interactions

There are several potentially significant interactions that may occur withamiodarone. The following is partial list of interactions that are most likely seen in veterinarypatients: amiodarone may significantly increase the serum levels and/or pharmacologic effects ofanticoagulants, 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.

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