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JAMA Sep 2007Although amiodarone is approved by the US Food and Drug Administration only for refractory ventricular arrhythmias, it is one of the most frequently prescribed... (Review)
Review
CONTEXT
Although amiodarone is approved by the US Food and Drug Administration only for refractory ventricular arrhythmias, it is one of the most frequently prescribed antiarrhythmic medications in the United States.
OBJECTIVE
To evaluate and synthesize evidence regarding optimal use of amiodarone for various arrhythmias.
EVIDENCE ACQUISITION
Systematic search of MEDLINE to identify peer-reviewed clinical trials, randomized controlled trials, meta-analyses, and other studies with clinical pertinence. The search was limited to human-participant, English-language reports published between 1970 and 2007. Amiodarone was searched using the terms adverse effects, atrial fibrillation, atrial flutter, congestive heart failure, electrical storm, hypertrophic cardiomyopathy, implantable cardioverter-defibrillator, surgery, ventricular arrhythmia, ventricular fibrillation, and Wolff-Parkinson-White. Bibliographies of identified articles and guidelines from official societies were reviewed for additional references. Ninety-two identified studies met inclusion criteria and were included in the review.
EVIDENCE SYNTHESIS
Amiodarone may have clinical value in patients with left ventricular dysfunction and heart failure as first-line treatment for atrial fibrillation, though other agents are available. Amiodarone is useful in acute management of sustained ventricular tachyarrythmias, regardless of hemodynamic stability. The only role for prophylactic amiodarone is in the perioperative period of cardiac surgery. Amiodarone may be effective as an adjunct to implantable cardioverter-defibrillator therapy to reduce number of shocks. However, amiodarone has a number of serious adverse effects, including corneal microdeposits (>90%), optic neuropathy/neuritis (< or =1%-2%), blue-gray skin discoloration (4%-9%), photosensitivity (25%-75%), hypothyroidism (6%), hyperthyroidism (0.9%-2%), pulmonary toxicity (1%-17%), peripheral neuropathy (0.3% annually), and hepatotoxicity (elevated enzyme levels, 15%-30%; hepatitis and cirrhosis, <3% [0.6% annually]).
CONCLUSION
Amiodarone should be used with close follow-up in patients who are likely to derive the most benefit, namely those with atrial fibrillation and left ventricular dysfunction, those with acute sustained ventricular arrhythmias, those about to undergo cardiac surgery, and those with implantable cardioverter-defibrillators and symptomatic shocks.
Topics: Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Drug Interactions; Humans
PubMed: 17878423
DOI: 10.1001/jama.298.11.1312 -
The Consultant Pharmacist : the Journal... Sep 2010To review the safety and efficacy of the newly approved, mixed-activity antiarrhythmic dronedarone (classes I-IV) versus its parent compound comparator, amiodarone... (Review)
Review
OBJECTIVE
To review the safety and efficacy of the newly approved, mixed-activity antiarrhythmic dronedarone (classes I-IV) versus its parent compound comparator, amiodarone (class III, with mixed activity).
DATA SOURCES
A MEDLINE/PUBMED (January 1966 to March 2010) and International Pharmaceutical Abstract (January 1975 to March 2010) search of English language papers in addition to a bibliographic search of retrieved papers.
STUDY SELECTION
All human studies of dronedarone, alone or in combination with amiodarone, were reviewed.
DATA SYNTHESIS
Approved in July 2009, dronedarone is a new antiarrhythmic agent indicated to reduce the risk of hospitalization for cardiac events in patients with paroxysmal or persistent atrial fibrillation or atrial flutter. Dronedarone has been viewed as a potential therapeutic alternative for amiodarone because of a lower risk for pulmonary, thyroid, and dermatologic adverse effects. Compared with amiodarone, dronedarone has poor bioavailability and a shorter terminal disposition half-life, which dictates a twice-daily dosing regimen. Furthermore, dronedarone failed to demonstrate superiority over amiodarone with respect to recurrence of atrial fibrillation in a comparative efficacy analysis. Dronedarone therapy is more costly and increases overall tablet burden. No dosage adjustments are required with dronedarone for renal impairment. Use of dronedarone is contraindicated in the presence of severe hepatic impairment. No serious organ-related toxicities (i.e., thyroid and pulmonary system) have been reported with use of dronedarone.
CONCLUSION
Dronedarone as a niche drug may be a reasonable theoretical alternative for patients who cannot tolerate amiodarone or have underlying comorbidities that contraindicate amiodarone use (e.g., pulmonary, thyroid disease). However, dronedarone has not been studied in the vast majority of indications and patient populations in which amiodarone has been studied.
Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Clinical Trials as Topic; Dronedarone; Drug Interactions; Humans
PubMed: 20876046
DOI: 10.4140/TCP.n.2010.555 -
Pacing and Clinical Electrophysiology :... Mar 1984
Review
Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Dose-Response Relationship, Drug; Drug Interactions; Half-Life; Humans; Pneumonia
PubMed: 6200855
DOI: 10.1111/j.1540-8159.1984.tb04897.x -
Clinics in Chest Medicine Mar 1990Amiodarone pulmonary toxicity is one of the most important examples of drug-induced lung disease by non-cancer chemotherapeutic agents. Current concepts suggest that... (Review)
Review
Amiodarone pulmonary toxicity is one of the most important examples of drug-induced lung disease by non-cancer chemotherapeutic agents. Current concepts suggest that patients may clinically present with an acute illness suggestive of a hypersensitivity picture or with a more chronic indolent course mimicking a malignant process. Likewise, the mechanism of amiodarone pulmonary toxicity suggests that at least two different pathways of toxicity exist: (1) an indirect mechanism characterized by influx of inflammatory or immune effector cells to the lung and (2) a direct toxic mechanism that results in lung parenchymal cell injury and a subsequent fibrotic response. Clearly, there is the potential for much crossover and interaction between the proposed pathways of toxicity in any given patient. A better understanding of the mechanism of amiodarone pulmonary toxicity will not only improve our diagnostic approaches to patients with this serious lung disorder, but will also provide the opportunity to develop unique therapeutic strategies that control the toxicity and potentially not interfere with the intended therapeutic efficacy of the drug.
Topics: Amiodarone; Humans; Lung; Lung Diseases; Phospholipids
PubMed: 2182274
DOI: No ID Found -
The New England Journal of Medicine Aug 1987
Topics: Amiodarone; Electrocardiography; Humans; Male; Middle Aged; Monitoring, Physiologic; Tachycardia
PubMed: 3614288
DOI: 10.1056/NEJM198708133170712 -
Clinical Pharmacokinetics Jun 1988
Review
Topics: Adult; Amiodarone; Arrhythmias, Cardiac; Child; Dose-Response Relationship, Drug; Humans; Monitoring, Physiologic; Time Factors
PubMed: 3293869
DOI: 10.2165/00003088-198814060-00001 -
Cleveland Clinic Journal of Medicine Mar 1998Amiodarone is a potent and versatile antiarrhythmic. Despite side effects involving the lungs, heart, thyroid, and other organs, it is effective in the treatment of... (Review)
Review
Amiodarone is a potent and versatile antiarrhythmic. Despite side effects involving the lungs, heart, thyroid, and other organs, it is effective in the treatment of refractory atrial and ventricular arrhythmias and it has unique safety in patients with coronary disease and left ventricular dysfunction. This review discusses the evolving indications for amiodarone and management of toxicities and drug interactions.
Topics: Amiodarone; Anti-Arrhythmia Agents; Humans
PubMed: 9540249
DOI: 10.3949/ccjm.65.3.159 -
Annals of Internal Medicine May 1995To review the pharmacology, electrophysiology, and toxicity of amiodarone and to discuss the clinical results produced when amiodarone is used as therapy for patients... (Review)
Review
PURPOSE
To review the pharmacology, electrophysiology, and toxicity of amiodarone and to discuss the clinical results produced when amiodarone is used as therapy for patients with atrial fibrillation, patients with nonsustained ventricular tachycardia and cardiomyopathy, patients who have recently had myocardial infarctions, and patients who have survived out-of-hospital cardiac arrest caused by ventricular tachycardia or ventricular fibrillation.
DATA SOURCES
Animal and clinical studies involving the pharmacology and electrophysiology of amiodarone and clinical trials in which amiodarone was used as therapy for the arrhythmias noted above were reviewed.
STUDY SELECTION
Relevant studies that reported on the efficacy and toxicity of amiodarone and on long-term therapy using amiodarone were reviewed, and their data were summarized. Reports of ongoing trials using amiodarone were also reviewed and summarized.
RESULTS
Amiodarone is useful for the treatment of many rhythm disturbances. Although side effects from this agent are common, serious toxicity necessitating discontinuation of therapy is infrequent. Unlike other antiarrhythmic agents, amiodarone has not been shown to increase mortality in any population studied.
CONCLUSION
Amiodarone, a unique antiarrhythmic agent with many pharmacologic actions, is effective in the treatment of a wide range of rhythm abnormalities. Several large, randomized trials will provide further information about the clinical usefulness of this agent.
Topics: Amiodarone; Animals; Arrhythmias, Cardiac; Electrophysiology; Heart; Hemodynamics; Humans
PubMed: 7702232
DOI: 10.7326/0003-4819-122-9-199505010-00008 -
The Annals of Pharmacotherapy Jun 1995To discuss the role of amiodarone for the maintenance of normal sinus rhythm in patients with atrial fibrillation (AF) and review the clinical trial data evaluating the... (Review)
Review
OBJECTIVE
To discuss the role of amiodarone for the maintenance of normal sinus rhythm in patients with atrial fibrillation (AF) and review the clinical trial data evaluating the efficacy and safety of amiodarone in patients with AF.
DATA SOURCES
A MEDLINE search was used to identify pertinent literature. Additional references were identified from the articles obtained in the search. Key search terms were atrial fibrillation, amiodarone, and sinus rhythm.
STUDY SELECTION
All studies available at the time the article was prepared evaluating the efficacy and safety of amiodarone in AF were included. In addition, review articles discussing the role of amiodarone in AF were selected.
DATA EXTRACTION
No large, prospective, randomized trials have been performed. Data from 8 nonrandomized and 2 randomized trials are reported. Information derived from review articles is discussed.
DATA SYNTHESIS
In patients with AF, maintenance of normal sinus rhythm is desirable to eliminate symptoms, improve functional capacity, and reduce the risk of thromboembolic complications. Class IA agents traditionally have been used; however, concerns about long-term effects on mortality have focused attention on other agents such as amiodarone. A number of nonrandomized, uncontrolled trials have found amiodarone to be effective for maintaining normal sinus rhythm in patients with AF that is refractory to conventional agents. Two randomized, nonblind trials have found amiodarone's efficacy to be equal to or superior to that of class IA drugs. The findings of these trials must be weighed, however, against the significant potential for toxicity and drug interactions associated with amiodarone. Cardiovascular toxicities, including proarrhythmic effects, appear to be relatively rare. In contrast, noncardiovascular effects are common and potentially serious.
CONCLUSION
Although the preliminary data using amiodarone in AF are encouraging, many questions remain unanswered. Prospective, randomized trials are needed to evaluate the long-term efficacy and safety of amiodarone in patients with AF. Studies also are needed to determine the optimal dosing regimen. Until these data are available, each patient must be evaluated individually, taking into account the relative benefits and risks of therapy. Amiodarone may be particularly useful in patients with significant risks for proarrhythmia and those whose AF is refractory to traditional therapy.
Topics: Amiodarone; Atrial Fibrillation; Clinical Trials as Topic; Heart Rate; Humans; Risk Factors
PubMed: 7663033
DOI: 10.1177/106002809502900609 -
Journal of the American College of... Nov 1992
Topics: Amiodarone; Drug Evaluation; Humans; Myocardial Infarction
PubMed: 1401603
DOI: 10.1016/0735-1097(92)90358-t