Ventricular Arrhythmias PO Load: 800-1600 mg PO qDay for 1-3 weeks until response; once adequate arrhythmia control achieved, reduce dose to 600-800 mg/day for 1 mo; THEN reduce to maintenance dose Maintenance dose: 400 mg PO qDay IV 150 mg over first 10 min (15mg/min), followed by 360 mg over next 6 hr (1 mg/min), THEN 540 mg over remaining 18 hr (0.5 mg/min), for a total of 1000 mg over 24 hr before administering maintenance infusion Maintenance: 0.5 mg/min for a total 720 mg/24hr at a concentration of 1-6 mg/mL (360 mg/200mL), or 1.8 mg/mL Nexterone at rate of 278 mL/min Duration of therapy: May continue to administer 0.5 mg/min for 2-3 weeks regardless of patient's age, renal function or ventricular function Lower doses may be used for supraventricular arrhythmias. Daily doses may be divided. Close monitoring of the patient is recommended. Use the minimum effective dose. Elderly: Recommended to start dosing at the lower end of the dosing range because elderly may be predisposed to toxicity. Hepatic impairment: Dosage reduction may be necessary.

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 α- and β-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

Administration: Potentiation of antiarrhythmic drugs. Possible increased risk of adverse effects when used with anaesthetic agents. Monitor plasma levels of amiodarone when used with HIV protease inhibitors. Cimetidine may increase serum levels of amiodarone. Concurrent use may increase serum levels of ciclosporin. May increase risk of myopathy or rhabdomyolysis when used with HMG-CoA reductase inhibitors. Rifampin may reduce the serum levels of amiodarone. Potentially Fatal: Potentiates the effect of warfarin and other anticoagulants hence dose of warfarin generally needs to be reduced approx half. Raised plasma concentrations of digoxin, phenytoin and quinidine. Additive effect with beta-blockers and calcium-channel blockers (e.g. verapamil and diltiazem). Adult Dose: Close monitoring is recommended as amiodarone may worsen arrhythmia especially when used concurrently with other anti-arrhythmic drugs or drugs that prolong QT interval. May cause hypotension and bradycardia. May increase risk of liver toxicity. May cause visual disturbance/impairment; corneal refractive laser surgery is not recommended in patients on amiodarone treatment. May cause lung damage; monitor for pulmonary toxicity e.g. acute respiratory distress syndrome. Monitor liver functions regularly. May affect defibrillation or pacing thresholds of cardiac devices. Correct electrolyte imbalance before starting treatment. Caution when used in patients undergoing surgery. Avoid excessive sunlight exposure due to increased risk of photosensitivity. Hepatic impairment, thyroid disease, elderly. Lactation. Lactation: Excreted into breast milk; not recommended Renal Dose: Amiodarone is a class III antiarrhythmic agent which inhibits stimulation, prolongs action potential and refractory period in myocardial tissues. It also decreases AV conduction and sinus node function. Sinus rate is reduced by 15-20%, PR and QT intervals are increased. Amiodarone can cause marked sinus bradycardia or sinus arrest and heart block. In acute IV doses, amiodarone may exert a mild negative inotropic effect.

Hypersensitivity to amiodarone or iodine. Severe sinus node dysfunction, 2nd and 3rd degree heart block (except in patients with a functioning artificial pacemaker), cardiogenic shock, pregnancy.

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 of Amiodarone therapy are related to the lungs. These reactions can be fatal. Patients should report any symptoms of cough, fever, or painful breathing. Although quite rare, fatal liver toxicity may occur with Amiodarone therapy. Reversible corneal microdeposits (sometimes with night glare), rarely impaired vision due to optic neuritis; peripheral neuropathy and myopathy (usually reversible on withdrawal); bradycardia and conduction disturbances; phototoxicity and rarely persistent skin discolouration; hypothyroidism, hyperthyroidism; raised serum transaminases; jaundice, hepatitis and cirrhosis are reported. Other rare complaints are nausea, vomiting, metallic taste, tremor, sweating, vertigo, headache, sleeplessness, fatigue, alopecia, benign raised intracranial pressure, ataxia, rashes, vasculitis, renal involvement, thrombocytopenia, haemolytic or aplastic anaemia. In some cases, dose of Amiodarone may be reduced. In other cases, Amiodarone therapy may need to be stopped.

Should not be administered during pregnancy and lactation.

Precaution: Ventricular arrhythmias, Ventricular fibrillation, Ventricular tachycardia, Atrial fibrillation, Hypertrophic cardiomyopathy, Supraventricular arrhythmias

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 β-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.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Potassium channel blockers

May be taken with or without food. Take consistently w/ or w/o meals. Take w/ meals if high dose or to reduce GI discomfort. Reconstitution: To make solution for 1st rapid loading infusion or supplemental infusion: Add 3 ml of amiodarone HCl concentrate (50 mg/ml) to 100 ml of dextrose 5% to give a final conc of 1.5 g/ml; for slow infusion: Add 18 ml of amiodarone HCl concentrate (50 mg/ml) to 500 ml of dextrose 5% to give a final conc of 1.8 mg/ml; for subsequent maintenance infusions, diluted solutions with conc ranging from 1-6 mg/ml may be used. Solutions with conc ?2 mg/ml should be administered via a central venous catheter.

>10% Increased liver AST or ALT levels (3-20%; as high as 40-50% in some studies),Hypotension (16%),Dizziness (3-40%),Headache (3-40%),Malaise (3-40%),Abnormal gait/ataxia (3-40%),Fatigue (3-40%),Impaired memory (3-40%),Involuntary movement (3-40%),Sleep disturbances (3-40%),Photosensitivity (10-75%),Hypothyroidism (1-22%),Constipation (10-33%),Anorexia (10-33%) 1-10% CHF (3%),Bradycardia (3-5%),AV block (5%),SA node dysfunction (1-3%),Hyperthyroidism (3-10%),Hepatitis and cirrhosis (<3%),Visual disturbances (2-9%),Optic neuritis (1%) Frequency Not Defined Corneal microdeposits,Demyelinating polyneuropathy Potentially Fatal: Pulmonary toxicity including pulmonary fibrosis and interstitial pneumonitis, hepatotoxicity, thyrotoxicity. Ventricular arrhythmias, pulmonary alveolitis, exacerbation of arrhythmias and rare serious liver injury. Generally in patients with high doses and having preexisting abnormalities of diffusion capacity.