Amiodarone, adverse reaction

It has been reported that there is an increased risk of adverse reactions to amiodarone in patients undergoing anesthesia (SEDA-15, 171). However, in a retrospective survey of 12 patients who underwent anesthesia for urgent thyroidectomy due to amiodarone there were no anesthetic complications or deaths (227). 

The use of amiodarone in the prevention of atrial fibrillation after cardiac surgery has been reviewed (231). When an intravenous loading dose of amiodarone was used, bradycardia was a common adverse effect but was rarely severe enough to warrant withdrawal. When only oral amiodarone was used there were no serious adverse reactions. 

Cetnarowski AB, Rihn TL. A review of adverse reactions to amiodarone. Cardiovasc Rev Rep 1985 6 1206-22. 

McGovern B, Garan H, Kelly E, Ruskin JN. Adverse reactions during treatment with amiodarone hydrochloride. BMJ (1983) 287, 175-80. 

An 86-year-old man taking fiirosemide, digoxin, domperidone and sustained-release theophylline developed signs of theophylline toxicity when amiodarone 600 mg daily was given. After 9 days his serum theophylline levels had doubled, from about 16.8 to 35 mg/L. The toxicity disappeared when the theophylline was stopped. The reason for this adverse reaction is not understood but it has been suggested that amiodarone may reduce the metabolism of the theophylline by the liver. This is an isolated case and its general importance is uncertain. More study is needed. 

Pathophysiology Concentrations of amio-darone and desethylamiodarone were measured simultaneously in plasma and fat in 30 patients who had taken amiodarone for 3 months to 12 years [38 ]. Amiodarone concentrations in fat were 4—226 (mean 55) times higher than in plasma, and correlated with plasma concentrations (r = 0.68). Nine of 12 patients who had taken amiodarone for at least 2 years developed clinically important adverse reactions, predominantly hypothyroidism (n = 6), compared with two of 18 patients who had taken it for less time (RR = 6.75 95% Cl = 1.8, 26). The risk of adverse reactions did not correlate with amiodarone concentrations in plasma or fat. 

Immunologic Amiodarone is contraindicated in patients with hypersensitivity to intravenous contrast media. Three patients with previous reactions to contrast media had no adverse reactions during prolonged amiodarone treatment 100-200 mg/day [43 ]. Poor absorption of oral amiodarone and reactions to other components of contrast media besides iodine, causing histamine release, could explain this lack of cross-reactivity. 

In a meta-analysis of randomized controlled studies of dronedarone and amiodarone for prevention of recurrent atrial fibrillation, four placebo-controlled trials of dronedarone, four placebo-controlled trials of amiodarone, and one trial of dronedarone versus amiodarone were compared [61 ]. Amiodarone was superior to dronedarone in preventing recurrent atrial fibrillation, but there was a trend towards greater all-cause mortality (OR = 1.61 95% Cl = 0.97, 2.68) and more overall adverse events requiring drug withdrawal with amiodarone than with dronedarone (OR = 1.81 95% Cl = 1.33, 2.46). Among adverse reactions, thyroid toxicity was more frequent with amiodarone (7.5% versus 4.0%) whereas increased serum creatinine was more frequent with dronedarone (4.0% versus 0%). For every 1000 patients treated with dronedarone instead of amiodarone, the authors estimated that there were about... 

Pain There are a few cases reporting low back pain as a reaction to intravenous administration of amiodarone [19]. This effect, however, resolves after the discontinuation of the infusion. Notably intravenous and rarely oral administrations of amiodarone were related to several adverse effects. This may indicate that other constituents within the intravenous solution could be the possible causative agent. It was previously reported that an excipient used to stabilise aqueous formulations of amiodarone infusion - polysorbate-80 - could be implicated in a variety of adverse reactions. The proposed mechanism for epigastric and low back pain occurrence is a hypotensive response caused by polysorbate-80, which in turn results in transient secondary mesenteric ischaemia. A marked release of histamine is the cause of the resulting hypotension. However, amiodarone s vasodilating effect as a cause of the back pain cannot be totally excluded. 

Amiodarone commonly causes phototoxicity reactions (186,187). The risk of phototoxicity increases with the duration of the exposure. Window glass and sun screens do not give protection, although zinc or titanium oxide formulations and narrow band UVB photo therapy can help (188-190). For most patients this adverse effect will be no more than a nuisance, and the benefit of therapy may be worthwhile. However, in a few cases treatment may have to be withdrawn. Histological examination of skin biopsies shows intracytoplasmic inclusions of phospholipids (191). There has been a single report of a severe case of photosensitivity in conjunction with a syndrome resembling porphyria cutanea tarda, resulting in bullous lesions (192). 

It is unknown whether thyroid dysfunction (hypothyroidism or hyperthyroidism) is a result of the amiodarone, the iodine contained in the amiodarone, or another mechanism. The production of amiodarone-phospholipid complexes within organs has been proposed as the mechanism for some of this drug s adverse effects. The mechanism of the pulmonary toxicity seen following chronic use is also uncertain but is the result of a hypersensitivity reaction in some. 

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