When was amiodarone approved

Amiodarone is the only drug in modern FDA history , to be approved for use in the United States without undergoing any of the required randomized, clinical studies to show a drug is safe and effective before it is approved. In essence, there was nothing to lose for such patients who faced a likely death without some treatment to control V-fib. As a result, the FDA has never approved the use of Amiodarone for anything other than a treatment of last resort for persons with life-threatening V-fib.

Then how did Amiodarone come to be the most commonly prescribed treatment for A-fib, which is far less dangerous but far more common arrhythmia than V-fib? This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. This article has been cited by other articles in PMC. Abstract Amiodarone has emerged as the leading antiarrhythmic therapy for termination and prevention of ventricular arrhythmia in different clinical settings because of its proven efficacy and safety.

Keywords: amiodarone, ventricular fibrillation, unstable ventricular tachycardia. Introduction Amiodarone was developed originally as an antianginal agent in Belgium Labaz Inc. Pharmacology Pharmacokinetics The pharmacokinetics of amiodarone and its metabolites are complex. Electrophysiology The electrophysiologic effects of amiodarone are very complex, still incompletely understood and unlike any other antiarrhythmic drug.

Safety and tolerability Amiodarone has been reported to cause a variety of cardiac and extracardiac side effects, both in its oral and intravenous formulation Table 1. Table 1 Adverse effects during long-term amiodarone therapy.

Open in a separate window. Oral formulation Of the extracardiac adverse effects, pulmonary fibrosis is the most serious since it is potentially fatal. Intravenous formulation The predominant clinical adverse event associated with the intravenous administration of amiodarone is hypotension, caused by a negative inotropic effect and a decrease in systemic vascular resistance. Alternatives Oral formulation Dronedarone is a derivative of amiodarone with a similar electropharmacologic profile, but without iodine to eliminate the iodine-related adverse reactions.

Intravenous formulation Several practical difficulties arise when the current formulation of intravenous amiodarone has to be administered in an emergency setting. Summary Despite the well-understood toxicity of amiodarone, it remains the most effective and safe, in the short term, antiarrhythmic drug for ventricular arrhythmias.

Footnotes Disclosures The authors report no conflicts of interest in this work. References 1. Singh BN. Amiodarone: Historical development and pharmacologic profile. Am Heart J. Van Schepdael J, Solvay H. Presse Med. The effect of amiodarone, a new anti-anginal drug, on cardiac muscle. Br J Pharmacol. Clinical efficacy of amiodarone as an antiarrhythmic agent.

Am J Cardiol. Connolly SJ. Pharmacokinetics of amiodarone after intravenous and oral administration. Eur J Clin Pharmacol. Amiodarone pharmacokinetics. Pharmacology and pharmacokinetics of amiodarone. J Clin Pharmacol. Plasma levels of amiodarone after intravenous and oral administration. J Clin Chem Clin Biochem. Pollak PT. Clinical organ toxicity of antiarrhythmic compounds: ocular and pulmonary manifestations. Cellular electropharmacology of amiodarone. Cardiovasc Res.

Charlier R. Cardiac actions in the dog of a new antagonist of adrenergic excitation which does not produce competitive blockade of adrenoceptors. Acute and chronic effects of amiodarone on ventricular refractoriness, intraventricular conduction and ventricular tachycardia induction.

J Am Coll Cardiol. Frequency-dependent electrophysiologic effects of amiodarone in humans. Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation. N Engl J Med. Amiodarone as compared with lidocaine for shock resistant ventricular fibrillation.

Amiodarone is poorly effective for the acute termination of ventricular tachycardia. Ann Emerg Med. Intravenous amiodarone for the pharmacological termination of haemodynamically-tolerated sustained ventricular tachycardia: is bolus dose amiodarone an appropriate first-line treatment?

Emerg Med J. Clinical efficacy of intravenous amiodarone in the short-term treatment of recurrent sustained ventricular tachycardia and ventricular fibrillation. Br Heart J. Comparison of procainamide and lidocaine in terminating sustained monomorphic ventricular tachycardia. Dose-ranging study of intravenous amiodarone in patients with life-threatening ventricular tachyarrhythmias.

Intravenous amiodarone for recurrent sustained hypotensive ventricular tachyarrhythmias. Intravenous Amiodarone Multicenter Trial Group. Randomized, double-blind comparison of intravenous amiodarone and bretylium in the treatment of patients with recurrent, hemodynamically destabilizing ventricular tachycardia or fibrillation. Ventricular tachycardia and aggravation of Brugada ECG pattern in a patient with coronary artery disease and combined amiodarone and beta-blocker therapy.

Clin Res Cardiol. Unmasking of the Brugada syndrome phenotype during the acute phase of amiodarone infusion. Meta-analysis of the implantable cardioverter defibrillator secondary prevention trial. Eur Heart J.

Long-term comparison of the implantable cardioverter defibrillator versus amiodarone: eleven-year follow-up of a subset of patients in the Canadian Implantable Defibrillator Study CIDS Circulation. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. Effect of implantable defibrillators on arrhythmic events and mortality in the Multicenter Unsustained Tachycardia Trial.

Quantitative overview of randomized trials of amiodarone to prevent sudden cardiac death. Comparison of beta-blockers, amiodarone plus beta-blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators. Thyroid hormone and the cardiovascular system. Digoxin-quinidine and digoxinamiodarone interactions: frequency of occurrence and monitoring in Australian repatriation hospitals.

J Clin Pharm Ther. Potentially significant drug interactions of class III antiarrhythmic drugs. Drug Saf. Zocor [package insert]. West Pont, Pa. Use of sildenafil Viagra in patients with cardiovascular disease. Richard W. Sloan, M. Hospital and clinical associate professor in family and community medicine at the Milton S.

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Contact afpserv aafp. Want to use this article elsewhere? Get Permissions. Read the Issue. Sign Up Now. Previous: Diagnosis of Systemic Lupus Erythematossus. Next: Returning to Work While Breastfeeding. Dec 1, Issue. Amiodarone: Guidelines for Use and Monitoring. TABLE 1 Dosage Guidelines for Amiodarone Cordarone Indication Administration route and setting Dosage Potential adverse effects Life-threatening arrhythmia IV, inpatient treatment mg IV bolus over 10 minutes if necessary, bolus may be repeated in 10 to 30 minutes ; then 1 mg per minute for 6 hours; then 0.

Liver toxicity 1 5 Liver enzyme levels three times higher than normal Consider stopping amiodarone. Optic neuropathy Unknown 19 Ophthalmologic examination Consider stopping amiodarone; causal relationship is uncertain.

Minor effects Nausea, anorexia 30 2 History, physical examination Reduce dosage. TABLE 3 Important Amiodarone Cordarone Drug Interactions Drug Result of interaction Digoxin 22 Elevated digoxin plasma concentration Warfarin Coumadin 21 Elevated prothrombin time Simvastatin Zocor 24 Increased incidence of myopathy when simvastatin dosage is higher than 20 mg per day Sildenafil Viagra 25 Increased sildenafil plasma concentration Cyclosporine Sandimmune 4 Increased cyclosporine plasma concentration Antiarrhythmic drugs 4 Additive effects: possible elevated plasma concentrations of quinidine, disopyramide Norpace , flecainide Tambocor , propafenone Rythmol , and dofetilide Tikosyn Quinolones 23 Additive QT effect: possible increased risk of proarrhythmia Antidepressants 23 Increased plasma concentration of hepatically metabolized drugs: possible increased risk of proarrhythmia Information from references 4 and 21 through Read the full article.

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Navigate this Article. Life-threatening arrhythmia. IV, inpatient treatment. Hypotension, bradycardia, atrioventricular block. Ventricular arrhythmia.

Oral, inpatient treatment. Oral, inpatient or outpatient treatment. Serious effects. Stop amiodarone; initiate corticosteroid therapy. Free T 4 level, TSH level. Initiate antithyroid drug therapy; consider stopping amiodarone. Administer thyroid hormone supplementation. Liver enzyme levels three times higher than normal. Consider stopping amiodarone. Unknown Ophthalmologic examination. Consider stopping amiodarone; causal relationship is uncertain.

Physical examination, ECG. If severe, stop amiodarone or insert pacemaker. Minor effects. History, physical examination. Corneal microdeposits. Slit-lamp examination.

Blue discoloration of skin. Digoxin Elevated digoxin plasma concentration. Elevated prothrombin time. Increased sildenafil plasma concentration. Increased cyclosporine plasma concentration. Quinolones Additive QT effect: possible increased risk of proarrhythmia. Baseline assessment. Thyroid studies and liver transaminase levels.

Digoxin level, prothrombin time, and INR, when appropriate. Ophthalmologic examination if preexisting visual impairment. During outpatient loading.

Close surveillance of heart rate, especially during first week of treatment. Digoxin level as appropriate.