We sought to assess the odds of experiencing adverse effects with low dose amiodarone
therapy compared with placebo.
An estimate of the likelihood of experiencing amiodarone-related adverse effects with
exposure to low daily doses of the drug is lacking in the published reports, and little
information is available on adverse effect event rates in control groups not receiving
the drug.
Data from four published trials involving 1,465 patients were included in a meta-analysis
design. The criteria for inclusion were 1) double-blind, placebo-controlled design;
2) absence of a crossover design between patient groups; 3) mean follow-up of at least
12 months; 4) maintenance amiodarone dose < or = 400 mg/day; and 5) presence of an
explicit description of adverse effects. Data were pooled after testing for homogeneity
of treatment effects across trials, and summary odds ratios were calculated by the
Peto-modified Mantel-Haenszel method for each adverse effect.
The mean amiodarone dose per day ranged from 152 to 330 mg; 738 patients were randomized
to receive amiodarone and 727 placebo. Exposure to amiodarone in this dose range,
for a minimal duration of 12 months, resulted in odds similar to those of placebo
for hepatic and gastrointestinal adverse effects, but in significantly higher odds
than those of placebo (p < 0.05) for experiencing thyroid (odds ratio [OR] 4.2, 95%
confidence interval [CI] 2.0 to 8.7), neurologic (OR 2.0, 95% CI 1.1 to 3.7), skin
(OR 2.5, 95% CI 1.1 to 6.2), ocular (OR 3.4, 95% CI 1.2 to 9.6) and bradycardic (OR
2.2, 95% CI 1.1 to 4.3) adverse effects. A trend toward increased odds of pulmonary
toxicity was noted (OR 2.0, 95% CI 0.9 to 5.3), but this did not reach statistical
significance (p = 0.07). The unadjusted total incidence of drug discontinuation was
22.9% in the amiodarone group and 15.4% in the placebo group. The odds of discontinuing
the drug in the amiodarone group was approximately 1.5 times that of the placebo group
(OR 1.52, 95% CI 1.2 to 1.9) (p = 0.003).
Compared with placebo, there is a higher likelihood of experiencing several amiodarone-related
adverse effects with exposure to low daily doses of the drug. Thus, although low dose
amiodarone may be well tolerated, it is not free of adverse effects.