Authors
Elsa-Grace Giardina, MD, MS
Peter J Zimetbaum, MD
Section Editor
Mark S Link, MD
Deputy Editor
Brian C Downey, MD, FACC
All topics are updated as new evidence becomes available
and our peer review process is complete.
Literature review current through: Sep 2014. | This topic
last updated: Sep 29, 2014.
INTRODUCTION — Amiodarone has multiple effects on
myocardial depolarization and repolarization that make it an extremely
effective antiarrhythmic drug. Its primary effect is to block the potassium
channels, but it can also block sodium and calcium channels and the beta and
alpha adrenergic receptors. (See "Myocardial action potential and action
of antiarrhythmic drugs".)
The approved clinical use of amiodarone has been limited
to refractory ventricular arrhythmias because of a relatively high incidence of
side effects that can range in severity from mild to potentially lethal (table
1) [1]. The use of lower doses (200 to 300 mg/day) may allow amiodarone to be
given safely and effectively in atrial arrhythmias such as atrial fibrillation
or flutter. However, as will be described below, even low doses of therapy are
associated with significant adverse effects, particularly thyroid, pulmonary,
neurologic, skin, ocular, and bradycardic events (table 1) [2]. Many of these
effects are due to the tissue accumulation of amiodarone with long-term oral
therapy and are not seen with short-term intravenous therapy.
Guidelines for the use of amiodarone were published by
the North American Society of Pacing and Electrophysiology (NASPE) in 2000 [3].
It was estimated that the prevalence of side effects was as high as 15 percent
in the first year and as high as 50 percent with long-term therapy. On the
other hand, the need to stop amiodarone because of serious adverse effects is
thought to be about 20 percent. In a meta-analysis of trials of low-dose
therapy, there was a significantly higher rate of drug discontinuation with
amiodarone compared to placebo (22.9 versus 15.4 percent) [2].
The major side effects of amiodarone will be reviewed
here. The clinical uses of amiodarone, including recommendations for its use in
the treatment of various arrhythmias, are discussed separately. (See "Clinical
uses of amiodarone" and "Antiarrhythmic drugs to maintain sinus
rhythm in patients with atrial fibrillation: Recommendations" and
"Supportive data for advanced cardiac life support in adults with sudden
cardiac arrest", section on 'Amiodarone'.)
INTRAVENOUS AMIODARONE — Intravenous amiodarone is
primarily given for short-term management of serious ventricular arrhythmias.
It has a different electrophysiologic and pharmacologic profile from oral
amiodarone. (See "Clinical uses of amiodarone".)
Many of the adverse effects associated with oral
amiodarone described below are due to tissue accumulation of the drug with
long-term therapy and are not seen with short-term use of intravenous
amiodarone [4]. A major problem noted with the intravenous preparation is
hypotension, which occurs in as many as 26 percent of patients and has been
attributed to the solvents used in the preparation [5,6]. Hypotension does not
appear to occur with a preparation of amiodarone that employs an aqueous base
[7].
In a review of the published literature and a report from
the Intravenous Amiodarone Multicenter Investigators Group of patients with
frequent life-threatening ventricular arrhythmias, proarrhythmia was noted in 2
to 3 percent of patients treated with intravenous amiodarone; it is usually
manifest as torsades de pointes but ventricular fibrillation can occur [4,5].
In the multicenter study in which six of 342 patients developed proarrhythmia,
all had an exacerbating factor such as acute ischemia or an electrolyte imbalance
[5].
Other cardiac side effects (bradycardia, asystole, heart
failure, and shock), nausea, vomiting, and abnormal liver function tests
occurred in 1 to 5 percent of patients each [4,5]. Acute respiratory distress
syndrome is a rare complication. When given through peripheral intravenous
lines, local phlebitis was most likely when the amiodarone concentration
exceeded 2 mg/mL.
PULMONARY DISEASE — Pulmonary involvement is the toxic
effect responsible for most deaths associated with amiodarone therapy. This
issue is discussed in detail separately. (See "Amiodarone pulmonary
toxicity".)
Summarized briefly:
●Pulmonary toxicity generally correlates more closely
with the total cumulative dose than with serum drug levels [8]. As a result,
pulmonary toxicity usually occurs several months to as late as several years
after the initiation of amiodarone therapy [8]. However, there are anecdotal
cases of severe pulmonary toxicity developing within two to three weeks of
therapy with low cumulative doses [9].
●Initial reports in which patients were usually treated
with amiodarone doses ≥400 mg/day noted a 5 to 15 percent incidence of
pulmonary toxicity [1,10,11]. However, the incidence is lower with lower
maintenance doses [2,8,11]. This was best illustrated in a meta-analysis of
four randomized trials of 1465 patients in whom low dose amiodarone (mean 150
to 330 mg/day given to patients with heart failure or post-myocardial
infarction) was compared to placebo for a minimum of one year [2]. There was a
nonsignificant trend toward an increased incidence of pulmonary toxicity with
amiodarone (1.9 versus 0.7 percent, odds ratio [OR] 2.2, 95 percent confidence
interval [CI] 0.9 to 5.3).
●There are several different types of pulmonary toxicity.
Chronic interstitial pneumonitis is most common; other manifestations include
organizing pneumonia, acute respiratory distress syndrome, and a solitary
pulmonary mass. One characteristic finding in all patients exposed to
amiodarone is the presence of numerous foamy macrophages in the air spaces
(picture 1). These cells are filled with amiodarone-phospholipid complexes.
●A nonproductive cough and dyspnea are present in 50 of
75 percent of affected individuals at presentation. Pleuritic pain, weight
loss, fever (33 to 50 percent of cases), and malaise can also occur. The
physical examination often reveals bilateral inspiratory crackles, while
clubbing is not seen.
●Serial lung function studies are not helpful for
predicting pulmonary toxicity. Although the DLCO is often decreased in patients
with pulmonary toxicity, there is usually no premonitory change in DLCO among
asymptomatic patients in whom symptomatic disease subsequently develops. As a
result, the DLCO is not useful as a predictive index [12,13]. In one report,
for example, most asymptomatic patients with a fall in DLCO of more than 20
percent did not develop pulmonary toxicity over the next year despite continued
amiodarone therapy [13].
●The diagnosis of amiodarone pulmonary toxicity is one of
exclusion. The differential diagnosis of pulmonary processes that can present
similarly to amiodarone toxicity includes heart failure, infectious pneumonia,
pulmonary embolism, and malignancy.
●Treatment of amiodarone pulmonary toxicity consists
primarily of stopping amiodarone. Corticosteroid therapy (prednisone 40 to 60
mg per day, with a taper over two to six months) can be life saving for severe
cases and for patients with less severe disease in whom withdrawal of
amiodarone is not desirable. Due to its accumulation in fatty tissues and long
elimination half-life (25 to 100 days), pulmonary toxicity may initially
progress despite drug discontinuation and may recur upon steroid withdrawal.
Preexisting pulmonary disease — An association between
preexisting lung disease and the development of amiodarone pulmonary toxicity
has been reported in some series. However, it is possible that these patients
merely have limited pulmonary reserve and thus become symptomatic earlier in
their course than other individuals. (See "Amiodarone pulmonary
toxicity", section on 'Risk factors'.)
THYROID DYSFUNCTION — Thyroid dysfunction (including both
hypothyroidism and hyperthyroidism) is a common complication of amiodarone
therapy. Although initial reports using higher doses noted hyperthyroidism or
hypothyroidism in up to 20 percent of patients, the risk is lower (about 3 to 4
percent) when lower doses are used (table 1) [2]. Underlying thyroid status and
iodine intake appear to influence the incidence and type of thyroid dysfunction
seen with amiodarone therapy [14]. (See "Amiodarone and thyroid
dysfunction".)
In patients taking amiodarone who are also being treated
with warfarin, the consequences of amiodarone-induced thyroid dysfunction
include a significant influence on warfarin response. The effect of warfarin is
potentiated by thyrotoxicosis and attenuated in hypothyroidism [15]. In any
patient with amiodarone-induced thyroid dysfunction who is also taking warfarin,
the International Normalized Ratio (INR) should be monitored closely and
appropriate adjustments in warfarin dosing made. (See 'Drug interactions'
below.)
CARDIAC TOXICITY
Sinus bradycardia — Amiodarone can directly cause both
sinus bradycardia and AV nodal block, due primarily to its calcium channel
blocking activity. The overall incidence of bradycardic events has been about 5
percent (table 1) [3]. In the meta-analysis cited above of chronic low-dose
amiodarone (mean 150 to 330 mg/day), the incidence of bradycardic events was
significantly greater than with placebo (3.3 versus 1.4 percent, OR 2.2, 95 CI
1.1 to 4.3) [2].
Bradycardia requiring a permanent pacemaker with
amiodarone therapy appears to be a particular concern with amiodarone in
elderly patients with atrial fibrillation who have had a myocardial infarction
[16], and may also be of greater concern in women than in men [17]. Pacing to
maintain continuous and homogeneous activation of the atria in such patients
also may reduce the frequency of AF recurrence. (See "The role of
pacemakers in the prevention of atrial fibrillation".)
Ventricular arrhythmias — Of greater potential concern is
amiodarone-induced prolongation of repolarization and the QT interval due to
blockade of the potassium channels. Ventricular arrhythmias may arise in this
setting due to early afterdepolarization-dependent triggered activity. However,
the incidence of proarrhythmia is very low with amiodarone, with an incidence
of torsades de pointes below 1 percent [18]. In the meta-analysis of low-dose
therapy, there were no cases of torsades de pointes in the 738 patients treated
with amiodarone for at least one year [2].
However, amiodarone has much less of this proarrhythmic
effect than other class III drugs, such as sotalol, ibutilide, and dofetilide,
particularly when given in lower doses (table 1) [1,2,6]. Several factors
contribute to the rarity of TdP with amiodarone: lack of reverse use
dependence; concurrent blockade of the L-type calcium channels; and less heterogeneity
of ventricular repolarization (less QT dispersion). However, the exact
electrophysiologic mechanisms responsible for the low proarrhythmic activity of
amiodarone are incompletely understood [19,20].
Torsades de pointes associated with amiodarone therapy is
more likely to occur in women and is much more likely to occur with other
factors that can cause QT prolongation such as hypokalemia, hypomagnesemia, and
certain antiarrhythmic drugs, such as quinidine and procainamide [21]. Female
preponderance with torsades de pointes has also been noted with other
antiarrhythmic drugs, with noncardiac drugs, and with congenital long QT
syndrome. (See "Acquired long QT syndrome", section on 'Risk factors'
and "Clinical features of congenital long QT syndrome", section on
'Genotype'.)
Amiodarone does not worsen left ventricular systolic
function and can be used to treat ventricular arrhythmias in selected patients
with heart failure. (See "Ventricular arrhythmias in heart failure and
cardiomyopathy".)
Interaction with ICDs — Amiodarone may have important
interactions with implantable cardioverter-defibrillators (ICDs). It may slow
the ventricular tachycardia rate, possibly precluding its recognition by the
device, and its major metabolite desethylamiodarone increases the
defibrillation threshold in a dose-dependent fashion; this effect is seen with
monophasic and biphasic waveforms [22-25]. The NASPE guidelines for amiodarone
therapy recommend that, whenever amiodarone is initiated in a patient with an
ICD, a noninvasive ICD evaluation or an electrophysiology study should be
performed to test for adverse drug-device interactions once loading is complete
[3]. (See "General principles of the implantable
cardioverter-defibrillator", section on 'Antiarrhythmic drugs'.)
Toxicity in patients without an ICD — Since not all
patients at risk for sudden cardiac arrest (SCA) are eligible for, or have
access to implantable cardioverter defibrillators (ICD), the efficacy and
safety of amiodaronefor the prevention of SCA has been considered. A
meta-analysis of all randomized controlled trials examining the use of
amiodarone versus placebo/control for the prevention of SCD revealed that
amiodarone reduces the risk of SCA by 29 percent and cardiovascular death by 18
percent and is a viable alternative in patients who are not eligible for or who
do not have access to ICD therapy for the prevention of SCA. However,
amiodarone therapy is associated with a two- and fivefold increased risk of
pulmonary and thyroid toxicity respectively in this population [26].
Mortality — Amiodarone has not been thought to increase
mortality, even in patients with underlying heart failure or coronary heart
disease [27,28]. However, a significant increase in mortality has been
suggested in patients with New York Heart Association class III heart failure
who were treated with amiodarone. This possible effect was noted in a subset
analysis from the SCD-HeFT trial of patients with New York Heart Association
class II or III HF and a left ventricular ejection fraction ≤35 percent and, in
a preliminary post hoc analysis, from the VALIANT trial comparing valsartan and
captopril in patients with HF occurring within 10 days after an acute
myocardial infarction [28,29]. (See "Ventricular arrhythmias in heart failure
and cardiomyopathy", section on 'Type of arrhythmia' and "Angiotensin
converting enzyme inhibitors and receptor blockers in acute myocardial
infarction: Clinical trials".)
HEPATOTOXICITY — A transient rise in serum
aminotransferase concentrations occurs in approximately 25 percent (range 15 to
50 percent) of patients soon after amiodarone is begun [30]. The patients are
usually asymptomatic, but the drug should be discontinued if there is more than
a two-fold elevation [3]. Symptomatic hepatitis occurs in less than 3 percent
of patients; potential complications include cirrhosis and hepatic failure
[30,31]. As a result, it is recommended that liver function tests be monitored
at baseline and every six months [3].
Jaundice is an unusual side effect that may be due to
intrahepatic cholestasis [32,33]. Serum bilirubin concentrations may first
increase or continue to increase for a period of time after the drug is
discontinued [32,33]. These findings are consistent with the long half-life of
amiodarone (25 to 100 days).
The histopathologic features of amiodarone-induced
hepatotoxicity include Mallory bodies, steatosis, intralobular inflammatory
infiltrates, fibrosis, and phospholipidosis [30,34-37]. These changes are
similar to those in alcoholic liver disease. The presence of phospholipid-laden
lysosomal lamellar bodies on electron microscopy may help distinguish
amiodarone hepatotoxicity from alcoholic liver disease [35,36]. (See
"Clinical manifestations and diagnosis of alcoholic fatty liver disease
and alcoholic cirrhosis".)
Both direct hepatotoxicity and metabolic idiosyncrasy are
thought to contribute to amiodarone-induced hepatic injury [30,37].
●The phospholipidosis is thought to reflect an
interaction between phospholipid and amiodarone, leading to the formation of a
complex that prevents degradation of phospholipid molecules.
●Metabolic idiosyncrasy refers to the propensity of a
patient to produce toxic metabolites from a compound to a greater degree than
other individuals. The site of abnormal drug metabolism is probably the
hepatocyte. (See "Drugs and the liver: Metabolism and mechanisms of
injury", section on 'Metabolic'.)
Although the relation of hepatotoxicity to cumulative
dose and duration of therapy is uncertain, it is likely that cumulative dose
correlates with overall toxicity and, therefore, that maintenance doses should
be kept as low as possible. In the meta-analysis cited above of chronic
low-dose amiodarone (mean 150 to 330 mg/day), the incidence of hepatotoxicity
was low and not significantly different from placebo (1.2 versus 0.8 percent,
OR 1.2, 95 CI 0.4 to 3.3) [2].
OCULAR CHANGES
Corneal microdeposits — Corneal microdeposits occur in
most patients receiving long-term amiodarone therapy, while some patients also
develop lenticular opacities [38-40]. The corneal microdeposits are caused by
the secretion of amiodarone by the lacrimal gland with accumulation on the
corneal surface. They are identifiable on ophthalmologic examination as a
brownish whorl at the juncture of the lower 1/3 and upper 2/3 of the cornea and
have been described as resembling a cat's whiskers [38]. The formation of
microdeposits is dose-dependent; the changes are reversible within seven months
after amiodarone is discontinued [39].
Corneal microdeposits do not reduce visual acuity.
However, ocular symptoms occur in a small number of patients [38,39]. These
include halo vision (colored rings around lights), particularly at night, photophobia,
and blurred vision. The incidence was 6 percent in an early study compared to
only 1.5 percent in a later meta-analysis of trials of chronic low-dose
amiodarone (mean dose 150 to 330 mg/day) [2,39]. This value was still
significantly greater than seen with placebo (0.1 percent, OR 3.4, 95 CI 1.2 to
9.6).
The presence of microdeposits is not considered a
contraindication to continued amiodarone therapy, since visual acuity is rarely
affected [38,39]. In any patient with visual symptoms who is taking amiodarone,
other common factors (a change in refractive correction, progression of
age-related cataract, or increased intraocular pressure) should be considered
before attributing the change to the drug.
Optic neuropathy — Amiodarone has been reported to cause
optic nerve injury, with unilateral or bilateral visual loss that can progress
to permanent blindness [38,41]. The prevalence of this finding may be as high
as 1 to 2 percent after 10 years of therapy [38]. Histopathologic studies have
demonstrated lamellar inclusions in the large axons of the retrobulbar optic
nerve, suggesting a drug-induced lipidosis [42]. However, a causal relationship
to amiodarone use has not been clearly established. (See "Nonarteritic
anterior ischemic optic neuropathy: Epidemiology, pathogenesis, and
etiologies".)
Cessation of amiodarone or dose reduction is recommended
unless the arrhythmia is life-threatening and an alternative antiarrhythmic
drug is not available [38].
OTHER — Amiodarone has a number of other toxic effects
(table 1).
Skin reactions — Skin reactions are common with long-term
amiodarone therapy. These include photosensitivity, which can be treated with
avoidance of sun exposure and the use of sunblock, and a bluish-slate gray
discoloration of the skin (so-called "blue man syndrome"), which is
usually most prominent on the face (picture 2).
The NASPE guidelines suggested that photosensitivity
occurred in 25 to 75 percent of patients and skin discoloration in less than 10
percent (table 1) [3]. However, a much lower rate of 2.3 percent was noted in
the meta-analysis of trials of chronic low-dose amiodarone therapy (mean dose
150 to 300 mg/day) [2]. This value was still significantly greater than seen
with placebo (0.7 percent, OR 2.5, 95 CI 1.1 to 6.2).
The bluish-slate gray discoloration of the skin occurs in
1 to 3 percent of patients on chronic amiodarone therapy and appears to be due
to the deposition of lipofuscin in the dermis [43-45]. There may be a tissue
threshold for amiodarone in individual patients above which skin discoloration
appears and below which it fades [46]. Thus, patients disturbed by skin
pigmentation who are taking large doses (more than 400 mg/day)may notice
improvement in skin discoloration by reducing the dose.
There is no specific therapy for the skin discoloration,
but affected patients are advised to avoid sun exposure. Complete resolution
after cessation of amiodarone therapy may take one year or more [47].
Gastrointestinal side effects — Gastrointestinal side
effects associated with amiodarone therapy include nausea, vomiting, anorexia,
diarrhea, and constipation [2,3]. They have been described in up to 30 percent
of patients (table 1), mostly during the initial loading phase of therapy [3].
In the meta-analysis of trials of chronic low-dose amiodarone therapy,
gastrointestinal side effects were not significantly more frequent than with
placebo (4.2 versus 3.3 percent, OR 1.1, 95 CI 0.6 to 1.9) [2].
Neurologic dysfunction — Neurologic toxicity may take
many forms including tremor, ataxia, peripheral neuropathy with paresthesias,
and sleep disturbances [2,3]. These effects, which have been described in 3 to
30 percent of patients (table 1), appear to be dose-related, being more common
during initial loading or in patients requiring higher doses. In the
meta-analysis of trials of chronic low-dose amiodarone therapy (mean dose 150
to 330 mg/day), neurologic side effects were much less common than what was
reported in early studies that utilized higher doses of amiodarone, but still
significantly more frequent than with placebo (4.6 versus 1.9 percent, OR 2.0,
95% CI 1.1-3.7) [2]. A retrospective study of 707 patients in Olmsted County
treated with amiodarone arrived at a similar conclusion [48].
Genitourinary effects — Sterile epididymitis with pain or
swelling in the scrotum and sexual dysfunction has been described in a small
number of patients treated with amiodarone [49,50]. Among patients with
epididymitis, reducing the amiodarone dose can prevent unnecessary antibiotic
therapy and invasive urologic procedures.
Changes in serum lipids — Alterations in serum lipid
concentrations have been noted in some amiodarone-treated patients. Amiodarone
increases serum cholesterol and triglyceride concentrations, but also raises
serum high density lipoprotein cholesterol [51,52]. Given these
counterbalancing effects, it is uncertain if amiodarone has an adverse effect
on coronary risk.
How these changes occur is uncertain. The changes in
serum cholesterol and triglycerides resemble those seen in hypothyroidism,
suggesting that the reductions in plasma and tissue T3 may contribute. (See
"Lipid abnormalities in thyroid disease".)
USE IN PREGNANCY — Amiodarone may cause toxicity in
either the mother or the fetus. Its use in pregnancy is discussed elsewhere. (See
"Clinical uses of amiodarone", section on 'Use in pregnancy'.)
DRUG INTERACTIONS — Amiodarone can interfere with the
hepatic metabolism of several antiarrhythmic drugs (such as quinidine,
procainamide, and digoxin), possibly leading to supratherapeutic plasma
concentrations if the dose is not reduced. It also predictably interferes with
the metabolism of warfarin, often requiring at least a 25 percent reduction in
warfarin dose [53]. These interactions are particularly worrisome because they
may persist for as long as three months after the cessation of therapy due to
the long elimination half-life of amiodarone (25 to 100 days). (See
Lexi-Interact™ program included with UpToDate for additional information
including specific dose adjustments [or limits] and management suggestions).
The interaction between amiodarone and warfarin is
further complicated by the potential effects of amiodarone on thyroid function.
The effect of warfarin is potentiated by thyrotoxicosis and attenuated in
hypothyroidism [15]. Thyroid function should be reassessed in any patient on a
stable warfarin and amiodarone regimen if the International Normalized Ratio
(INR) changes unexpectedly. (See 'Thyroid dysfunction' above.)
FOLLOW-UP AND MONITORING — The long half-life of amiodarone
(25 to 100 days) and the potential severity of some of the adverse effects make
early recognition important. As a result, careful monitoring of patients taking
amiodarone is essential.
Oral amiodarone — The recommendations from the NASPE
guidelines, including routine laboratory testing, are summarized in the table
(table 2) [3].
Intravenous amiodarone — IV amiodarone is generally used
in the management of life-threatening ventricular arrhythmias or in critically
ill patients with AF. Thus, most patients receiving IV amiodarone are on
continuous electrocardiographic monitoring with frequent assessment of vital
signs. Such monitoring is appropriate in all patients due to the potential for
hypotension and arrhythmias (eg, torsades de pointes or bradycardia due to AV
block or conversion to sinus rhythm with sinus bradycardia). In addition, the
usual baseline laboratories should be obtained (table 2).
SUMMARY
●Intravenous amiodarone is primarily given for short-term
management of serious ventricular arrhythmias and has a different
electrophysiologic and pharmacologic profile from oral amiodarone. The one
common problem noted with intravenous amiodarone is hypotension, which can
occur in up to 26 percent of patients. However, many of the adverse effects
associated with oral amiodarone described below are due to tissue accumulation
of the drug with long-term therapy and are not seen with short-term use of
intravenous amiodarone. (See 'Intravenous amiodarone' above.)
●Pulmonary toxicity generally correlates more closely
with the total cumulative dose than with serum drug levels, usually occurring
months to years after the initiation of amiodarone therapy. Several different
types of pulmonary toxicity may result from chronic amiodarone use, including
chronic interstitial pneumonitis (the most common), organizing pneumonia, acute
respiratory distress syndrome, and a solitary pulmonary mass. A nonproductive
cough and dyspnea are present in the majority of affected individuals at
presentation, and pleuritic pain, weight loss, fever (33 to 50 percent of
cases), and malaise can also occur. The physical examination often reveals
bilateral inspiratory crackles. The diagnosis of amiodarone pulmonary toxicity
is one of exclusion. Treatment consists primarily of stopping amiodarone, with
corticosteroid therapy administered in patients with symptomatic pulmonary
toxicity. (See 'Pulmonary disease' above and "Amiodarone pulmonary toxicity".)
●Thyroid dysfunction (including both hypothyroidism and
hyperthyroidism) is a common complication of amiodarone therapy, occurring in
about 3 to 4 percent of patients when lower doses (<400 mg/day) are used
(table 1). Underlying thyroid status and iodine intake appear to influence the
incidence and type of thyroid dysfunction seen with amiodarone therapy. (See
'Thyroid dysfunction' above and "Amiodarone and thyroid
dysfunction".)
●In up to 5 percent of patients, amiodarone can directly
cause both sinus bradycardia and AV nodal block, due primarily to its calcium
channel blocking activity. (See 'Sinus bradycardia' above.)
●There is a theoretical concern for proarrhythmia with
the use of amiodarone because of its prolongation of repolarization and the QT
interval due to blockade of the potassium channels. However, the incidence of
proarrhythmia is very low with amiodarone, with an incidence of torsades de
pointes below 1 percent per year. When torsades de pointes does occurs with the
use of amiodarone, it is much more likely to occur with other factors that can
cause QT prolongation such as hypokalemia, hypomagnesemia, and concomitant use
of certain other antiarrhythmic drugs. (See 'Ventricular arrhythmias' above.)
●A transient rise in serum aminotransferase
concentrations occurs in approximately 25 percent (range 15 to 50 percent) of
patients soon after amiodarone is begun. However, symptomatic hepatitis occurs
in less than 3 percent of patients, and potential complications such as
cirrhosis and hepatic failure occur very infrequently. Although the relation of
hepatotoxicity to cumulative dose and duration of therapy is uncertain, it is
likely that cumulative dose correlates with overall toxicity. While patients
are usually asymptomatic, the drug should be discontinued if there is more than
a twofold elevation in serum aminotransferases. (See'Hepatotoxicity' above.)
●Corneal microdeposits occur in most patients receiving
long-term amiodarone therapy, while some patients also develop lenticular opacities.
While corneal microdeposits do not reduce visual acuity, ocular symptoms may
occur, including halo vision (colored rings around lights), photophobia, and
blurred vision. The presence of microdeposits is not considered a
contraindication to continued amiodarone therapy since visual acuity is rarely
affected. (See 'Corneal microdeposits' above.)
●A variety of other side effects can manifest with the
chronic use of amiodarone, including dermatologic (photosensitivity and skin
discoloration), gastrointestinal (nausea, vomiting, anorexia, diarrhea,
constipation), neurologic (tremor, ataxia), genitourinary (epididymitis), and
altered lipid concentrations. (See 'Other' above.)
●Amiodarone can interfere with the hepatic metabolism of
several antiarrhythmic drugs (such as quinidine, procainamide, and digoxin),
possibly leading to supratherapeutic plasma concentrations if the dose is not
reduced. It also predictably interferes with the metabolism of warfarin, often
requiring at least a 25 percent reduction in warfarin dose. (See 'Drug
interactions' above.)
●The long half-life of amiodarone (25 to 100 days) and
the potential severity of some of the adverse effects make early recognition
important. As a result, careful monitoring of patients taking amiodarone is
essential (table 2). (See 'Follow-up and monitoring' above.)
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