PACET

AMIODARONE HYDROCHLORIDE

Because of its life-threatening side effects and the substantial management difficulties associated with its use, Amiodarone is indicated only for the treatment of the following documented, life threatening recurrent ventricular arrhythmias when these have not responded to documented adequate doses of other available antiarrhythmics or when alternative agents could not be tolerated. Recurrent ventricular fibrillation. Recurrent hemodynamically unstable ventricular tachycardia. As is the case for other antiarrhythmic agents, there is no evidence from controlled trials that the use of Amiodarone Tablets favorably affects survival. Amiodarone should be used only by physicians familiar with and with access to (directly or through referral) the use of all available modalities for treating recurrent life threatening ventricular arrhythmias, and who have access to appropriate monitoring facilities, including in-hospital and ambulatory continuous electrocardiographic monitoring and electrophysiologictechniques. Because of the life-threatening nature of the arrhythmias treated, potential interactions with prior therapy, and potential exacerbation of the arrhythmia, initiation of therapy with Amiodarone should be carried out in the hospital.

Potassium channel blockers

In animals, Amiodarone HCl is effective in the prevention or suppression of experimentally induced arrhythmias. The antiarrhythmic effect of Amiodarone may be due to at least two major properties: A prolongation of the myocardial cell-action potential duration and refractory period Non-competitive antagonism of 8- and 8-adrenoceptors. Amiodarone prolongs the duration of the action potential of all cardiac fibers while causing minimal reduction of dV/dt (maximal upstroke velocity of the action potential). The refractory period is prolonged in all cardiac tissues. Amiodarone increases the cardiac refractory period without influencing resting membrane potential, except in automatic cells where the slope of the prepotential is reduced, generally reducing automaticity. These electrophysiologic effects are reflected in a decreased sinus rate of 15 to 20%, increased PR and QT intervals of about 10%, the development of U-waves, and changes in T-wave contour. These changes should not require discontinuation of Amiodarone as they are evidence of its pharmacological action, although Amiodarone can cause marked sinus bradycardia or sinus arrest and heart block. On rare occasions, QT prolongation has been associated with worsening of arrhythmia

Oral dose is 200 mg 3 times daily for 1 week reduced to 200 mg twice daily or the minimum required to control arrhythmia.

Amiodarone may interact with 8- blockers, calcium channel blockers, digoxin, flecainide, procainamide, quinidine, tricyclic antidepressants, warfarin and dextromethorphan.

Amiodarone is contraindicated in patients with cardiogenic shock; severe sinus-node dysfunction, causing marked sinus bradycardia; second- or third degree atrioventricular block; and when episodes of bradycardia have caused syncope (except when used in conjunction with a pacemaker). Amiodarone is contraindicated in patients with a known hypersensitivity to the drug or to any of its components, including iodine.

The most severe side effects are any symptoms of cough, fever, or painful breathing, reversible corneal microdeposits, impaired vision due to optic neuritis, peripheral neuropathy, bradycardia and conduction disturbances, phototoxicity and rarely persistent skin discoloration, hypothyroidism, hyperthyroidism, raised serum transaminases, jaundice, hepatitis and cirrhosis etc.

Should not be administered during pregnancy and lactation.

There have been cases, some fatal, of Amiodarone overdose. In addition to general supportive measures, the patient's cardiac rhythm and blood pressure should be monitored, and if bradycardia ensues, a 8-adrenergic agonist or a pacemaker may be used. Hypotension with inadequate tissue perfusion should be treated with positive inotropic and/or vasopressor agents. Neither Amiodarone nor its metabolite is dialyzable. The acute oral LD50 of Amiodarone HCl in mice and rats is greater than 3,000 mg/kg.