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JACC. Clinical Electrophysiology Aug 2022
Topics: Amiodarone; Arrhythmias, Cardiac; Drug-Related Side Effects and Adverse Reactions; Humans
PubMed: 35981796
DOI: 10.1016/j.jacep.2022.07.002 -
European Review For Medical and... Dec 2018The aim of the study was to examine the safety and efficacy of dronedarone in patients with a history of atrial fibrillation and amiodarone-induced hyperthyroidism.
OBJECTIVE
The aim of the study was to examine the safety and efficacy of dronedarone in patients with a history of atrial fibrillation and amiodarone-induced hyperthyroidism.
PATIENTS AND METHODS
We conducted a prospective study to evaluate the use of amiodarone and dronedarone in 124 patients with a history of paroxysmal atrial fibrillation who had no additional structural heart disease. All patients received amiodarone 200 mg qd. Out of 124 patients, 56 (45%) switched to dronedarone 400 mg bid due to amiodarone-induced hyperthyroidism and the remaining 68 patients (55%), with normal thyroid function, continued to receive amiodarone. The follow-up period was 12 months, and the patients were regularly monitored.
RESULTS
The primary outcome after 6 months dronedarone and amiodarone group was 56 and 68, including 38 (68%) and 54 (79.4%) (Odds ratio [OR] = 1.17, 95% confidence interval [95% CI] = 0.68-2.02) patients with sinus rhythm (SR) and 18 (32.14%) and 14 (28.6%) (odds ratio [OR] = 0.64, confidence interval [95% CI] = 0.29-1.40) patients with atrial fibrillation (AF). The secondary outcome after 12 months showed significant difference in thyroid function in the dronedarone group. Out of 46 patients, 24 (56.18%) patients reduced hyperthyroidism compared to the amiodarone group; out of 68, 6 (8.9%) patients were observed to have hyperthyroidism. At 12 months, there were 24 (43%) and 22 (62%) (odds ratio [OR] = 0.75, confidence interval [95% CI] = 0.38-1.49) patients with SR, and 32 (57%) and 26 (38%) (odds ratio [OR] = 0.67, confidence interval [95% CI] = 0.36-1.25) patients with AF.
CONCLUSIONS
In our study, dronedarone appears to be a good therapeutic option in the treatment of atrial fibrillation in patients with amiodarone-induced hyperthyroidism. However, long-term studies are needed to estimate the efficacy and toxicity of both drugs.
Topics: Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Dronedarone; Female; Humans; Hyperthyroidism; Male; Middle Aged; Prospective Studies
PubMed: 30556893
DOI: 10.26355/eurrev_201812_16551 -
Current Cardiology Reviews Nov 2014Dronedarone is an amiodarone analog that differs structurally from amiodarone in that the iodine moiety was removed and a methane-sulfonyl group was added. These... (Review)
Review
Dronedarone is an amiodarone analog that differs structurally from amiodarone in that the iodine moiety was removed and a methane-sulfonyl group was added. These modifications reduce thyroid and other end-organ adverse effects and makes dronedarone less lipophilic, with a shorter half-life. Dronedarone has been shown to prevent atrial fibrillation/ flutter (AF/AFl) recurrences in several multi-center trials. In addition to its rhythm control properties, dronedarone has rate control properties. In patients with decompensated heart failure, dronedarone treatment increased mortality and cardiovascular hospitalizations. When dronedarone was used in elderly high risk AF/AFl patients, excluding those with advanced heart failure, cardiovascular hospitalizations were significantly reduced. The results of the PALLAS trial suggest that dronedarone should not be used in the long-term treatment of patients with permanent AF. Post-marketing data have demonstrated rare hepatic toxicity to be associated with dronedarone use. Updated practice and regulatory guidelines have positioned dronedarone as a front-line antiarrhythmic in many patients with AF/Fl. However, the drug should not be used in patients with advanced heart failure and in patients who develop permanent AF.
Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Dronedarone; Half-Life; Heart Failure; Hospitalization; Humans; Randomized Controlled Trials as Topic; Risk; Secondary Prevention
PubMed: 24821656
DOI: 10.2174/1573403x10666140513110247 -
Journal of Cellular and Molecular... Oct 2017Drug-induced ion channel trafficking disturbance can cause cardiac arrhythmias. The subcellular level at which drugs interfere in trafficking pathways is largely...
Drug-induced ion channel trafficking disturbance can cause cardiac arrhythmias. The subcellular level at which drugs interfere in trafficking pathways is largely unknown. K 2.1 inward rectifier channels, largely responsible for the cardiac inward rectifier current (I ), are degraded in lysosomes. Amiodarone and dronedarone are class III antiarrhythmics. Chronic use of amiodarone, and to a lesser extent dronedarone, causes serious adverse effects to several organs and tissue types, including the heart. Both drugs have been described to interfere in the late-endosome/lysosome system. Here we defined the potential interference in K 2.1 backward trafficking by amiodarone and dronedarone. Both drugs inhibited I in isolated rabbit ventricular cardiomyocytes at supraclinical doses only. In HK-KWGF cells, both drugs dose- and time-dependently increased K 2.1 expression (2.0 ± 0.2-fold with amiodarone: 10 μM, 24 hrs; 2.3 ± 0.3-fold with dronedarone: 5 μM, 24 hrs) and late-endosomal/lysosomal K 2.1 accumulation. Increased K 2.1 expression level was also observed in the presence of Na 1.5 co-expression. Augmented K 2.1 protein levels and intracellular accumulation were also observed in COS-7, END-2, MES-1 and EPI-7 cells. Both drugs had no effect on K 11.1 ion channel protein expression levels. Finally, amiodarone (73.3 ± 10.3% P < 0.05 at -120 mV, 5 μM) enhanced I upon 24-hrs treatment, whereas dronedarone tended to increase I and it did not reach significance (43.8 ± 5.5%, P = 0.26 at -120 mV; 2 μM). We conclude that chronic amiodarone, and potentially also dronedarone, treatment can result in enhanced I by inhibiting K 2.1 degradation.
Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; COS Cells; Cell Line, Tumor; Cells, Cultured; Chlorocebus aethiops; Dronedarone; HEK293 Cells; Humans; Ion Channel Gating; Mice; Myocytes, Cardiac; Potassium Channels, Inwardly Rectifying; Rabbits
PubMed: 28425222
DOI: 10.1111/jcmm.13172 -
Postgraduate Medical Journal Mar 2000Although amiodarone is regarded as a highly effective anti-arrhythmic agent, its use may lead to alterations in thyroid gland function and/or thyroid hormone metabolism,... (Review)
Review
Although amiodarone is regarded as a highly effective anti-arrhythmic agent, its use may lead to alterations in thyroid gland function and/or thyroid hormone metabolism, partly because of its rich iodine content. Patients treated with amiodarone may manifest altered thyroid hormone profile without thyroid dysfunction, or they may present with clinically significant amiodarone-induced hypothyroidism or amiodarone-induced thyrotoxicosis. The former results from the inability of the thyroid to escape from the Wolff-Chaikoff effect. It prevails in areas with high dietary iodine intake, and it is readily managed by discontinuation of amiodarone or thyroid hormone replacement. Amiodarone-induced thyrotoxicosis occurs more frequently in areas with low iodine intake; it may arise from iodine-induced excessive thyroid hormone synthesis (type I) or destructive thyroiditis with release of preformed hormones (type II). Type I should be treated with thionamides alone or in combination with potassium perchlorate, whereas type II benefits from treatment with glucocorticoids. Surgery may be a feasible option for patients who require long-term amiodarone treatment.
Topics: Amiodarone; Anti-Arrhythmia Agents; Humans; Thyroid Diseases
PubMed: 10684321
DOI: 10.1136/pmj.76.893.133 -
American Journal of Veterinary Research Mar 2006To determine the clinical effects and pharmacokinetics of amiodarone after single doses of 5 mg/kg administered orally or intravenously. (Clinical Trial)
Clinical Trial
OBJECTIVE
To determine the clinical effects and pharmacokinetics of amiodarone after single doses of 5 mg/kg administered orally or intravenously.
ANIMALS
6 healthy adult horses.
PROCEDURE
In a cross over study, clinical signs and electrocardiographic variables were monitored and plasma and urine samples were collected. A liquid chromatography-mass spectrometry method was used to determine the percentage of protein binding and to measure plasma and urine concentrations of amiodarone and the active metabolite desethylamiodarone.
RESULTS
No adverse clinical signs were observed. After IV administration, median terminal elimination half-lives of amiodarone and desethylamiodarone were 51.1 and 75.3 hours, respectively. Clearance was 0.35 L/kg x h, and the apparent volume of distribution for amiodarone was 31.1 L/kg. The peak plasma desethylamiodarone concentration of 0.08 microg/mL was attained 2.7 hours after IV administration. Neither parent drug nor metabolite was detected in urine, and protein binding of amiodarone was 96%. After oral administration of amiodarone, absorption of amiodarone was slow and variable; bioavailability ranged from 6.0% to 33.7%. The peak plasma amiodarone concentration of 0.14 microg/mL was attained 7.0 hours after oral administration and the peak plasma desethylamiodarone concentration of 0.03 microg/mL was attained 8.0 hours after administration. Median elimination half-lives of amiodarone and desethylamiodarone were 24.1 and 58.6 hours, respectively.
CONCLUSION AND CLINICAL RELEVANCE
Results indicate that the pharmacokinetic distribution of amiodarone is multicompartmental. This information is useful for determining treatment regimens for horses with arrythmias. Amiodarone has low bioavailability after oral administration, does not undergo renal excretion, and is highly protein-bound in horses.
Topics: Administration, Oral; Amiodarone; Animals; Anti-Arrhythmia Agents; Area Under Curve; Biological Availability; Cross-Over Studies; Female; Hemibody Irradiation; Horses; Injections, Intravenous
PubMed: 16506906
DOI: 10.2460/ajvr.67.3.448 -
Clinical Interventions in Aging Apr 2010Dronedarone has been developed for treatment of atrial fibrillation (AF) or atrial flutter (AFL). It is an amiodarone analogue but noniodinized and without the same... (Review)
Review
BACKGROUND
Dronedarone has been developed for treatment of atrial fibrillation (AF) or atrial flutter (AFL). It is an amiodarone analogue but noniodinized and without the same adverse effects as amiodarone.
OBJECTIVE AND METHODS
This is a review of 7 studies (DAFNE, ADONIS, EURIDIS, ATHENA, ANDROMEDA, ERATO and DIONYSOS) on dronedarone focusing on efficacy, safety and prevention of stroke. There was a dose-finding study (DAFNE), 3 studies focusing on maintenance of sinus rhythm (ADONIS, EURIDIS and DIONYSOS), 1 study focusing on rate control (ERATO) and 2 studies investigating mortality and morbidity (ANDROMEDA and ATHENA).
RESULTS
The target dose for dronedarone was established in the DAFNE study to be 400 mg twice daily. Both EURIDIS and ADONIS studies demonstrated that dronedarone was superior to placebo for maintaining sinus rhythm. However, DIONYSOS found that dronedarone is less efficient at maintaining sinus rhythm than amiodarone. ERATO concluded that dronedarone reduces ventricular rate in patients with chronic AF. The ANDROMEDA study in patients with severe heart failure was discontinued because of increased mortality in dronedarone group. Dronedarone reduced cardiovascular hospitalizations and mortality in patients with AF or AFL in the ATHENA trial. Secondly, according to a post hoc analysis a significant reduction in stroke was observed (annual rate 1.2% on dronedarone vs 1.8% on placebo, respectively [hazard ratio 0.66, confidence interval 0.46 to 0.96, P = 0.027]). In total, 54 cases of stroke occurred in 3439 patients (crude rate 1.6%) receiving dronedarone compared to 76 strokes in 3048 patients on placebo (crude rate 2.5%), respectively.
CONCLUSION
Dronedarone can be used for maintenance of sinus rhythm and can reduce stroke in patients with AF who receive usual care, which includes antithrombotic therapy and heart rate control.
Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Dose-Response Relationship, Drug; Dronedarone; Humans; Stroke
PubMed: 20396635
DOI: 10.2147/cia.s8883 -
Digestive Diseases (Basel, Switzerland) 1997
Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Fatal Outcome; Humans; Liver; Male; Tachycardia, Ventricular
PubMed: 9359019
DOI: 10.1159/000171606 -
Archivos de Cardiologia de Mexico Apr 2022
Topics: Amiodarone; Anti-Arrhythmia Agents
PubMed: 34544115
DOI: 10.24875/ACM.20000552 -
Cleveland Clinic Journal of Medicine Jul 2003Amiodarone causes thyrotoxicosis in 3% of US patients who use it. Two types of amiodarone-induced thyrotoxicosis are recognized, designated type 1 and type 2, based on... (Review)
Review
Amiodarone causes thyrotoxicosis in 3% of US patients who use it. Two types of amiodarone-induced thyrotoxicosis are recognized, designated type 1 and type 2, based on whether or not the patient had a preexisting thyroid disorder. Distinguishing between the two can be difficult, but it is important for providing appropriate therapy promptly.
Topics: Amiodarone; Anti-Arrhythmia Agents; Antithyroid Agents; Humans; Iodine; Practice Guidelines as Topic; Thyroidectomy; Thyrotoxicosis
PubMed: 12882384
DOI: 10.3949/ccjm.70.7.624