Amiodarone

What it is

Amiodarone is a synthetic iodine-containing benzofuran taken as 200 mg tablets or given intravenously. It is classed as a class III antiarrhythmic but acts on sodium, potassium and calcium channels and on sympathetic receptors as well. It is highly fat-soluble and about 96% protein-bound, so it builds up in fat, liver, lung and other tissues. Its terminal elimination half-life averages about 58 days, so it stays in the body for months after the last dose.

What the research says

The evidence is that amiodarone suppresses arrhythmias but has not been shown to prolong life. A meta-analysis of individual data from 6,553 patients in 13 randomised trials after myocardial infarction or in heart failure found total mortality reduced by 13% (odds ratio 0.87) and arrhythmic or sudden death by 29%. But the largest single placebo-controlled trial in heart failure, SCD-HeFT (2,521 patients), found no survival benefit at all (hazard ratio 1.06). In out-of-hospital cardiac arrest a 3,026-patient placebo-controlled trial found no significant increase in survival to discharge. For atrial fibrillation, amiodarone roughly halves recurrence (Cochrane risk ratio 0.52) but Cochrane also found a 6.7-fold increase in withdrawals for adverse effects. The harms are the dominant fact about this drug: the FDA label reserves it for life-threatening arrhythmias.

Evidence grade: Well established.

How it works

Drug class: Class III antiarrhythmic (iodinated benzofuran) with electrophysiologic actions of all four Vaughan Williams classes

Amiodarone slows electrical signalling in the heart. It blocks potassium channels so each heartbeat's electrical recovery (the action potential) lasts longer, and it also blocks sodium and calcium channels and dampens the effect of adrenaline on the heart. Together these effects slow the sinus and AV nodes and make abnormal rhythms harder to sustain. Because the molecule is fat-soluble and contains iodine, it accumulates in tissues over weeks and leaves them over months. (Source 1)

Boxed warning

WARNING: PULMONARY, HEPATIC and CARDIAC TOXICITY Amiodarone hydrochloride is intended for use only in patients with the indicated life-threatening arrhythmias because its use is accompanied by substantial toxicity [see Indications and Usage (1) ]. Amiodarone hydrochloride can cause pulmonary toxicity (hypersensitivity pneumonitis or interstitial/alveolar pneumonitis) that has resulted in clinically manifest disease at rates as high as 17% in some series of patients. Pulmonary toxicity has been fatal about 10% of the time. Obtain a baseline chest X-ray and pulmonary-function tests, including diffusion capacity, when amiodarone hydrochloride therapy is initiated. Repeat history, physical exam, and chest X-ray every 3 to 6 months [see Warnings and Precautions 5.2) ]. Amiodarone hydrochloride can cause hepatoxicity, which can be fatal. Obtain baseline and periodic liver transaminases and discontinue or reduce dose if the increase exceeds three times normal, or doubles in a patient with an elevated baseline. Discontinue amiodarone hydrochloride if the patient experiences signs or symptoms of clinical liver injury [see Warnings and Precautions (5.3) ] . Amiodarone hydrochloride can exacerbate arrhythmias. Initiate amiodarone hydrochloride in a clinical setting where continuous electrocardiograms and cardiac resuscitation are available [see Warnings and Precautions (5.4) ].

(Source 2)

What it is used for

• This is the only indication the US tablet label carries, and the label itself says it is reserved for life-threatening arrhythmias because of substantial toxicity. Arrhythmia suppression is well documented, but no placebo-controlled trial has shown amiodarone prolongs life in this setting. Evidence: limited. (Source 2)
• A 3,026-patient double-blind trial found survival to hospital discharge of 24.4% with amiodarone versus 21.0% with placebo, a 3.2 percentage point difference that was not statistically significant (P=0.08). Neurologic outcome was similar. Evidence: disputed. (Source 3)
• A meta-analysis of 13 trials found a 13% reduction in total mortality and 29% in arrhythmic death, but the largest individual trial (SCD-HeFT, 2,521 patients) found no survival benefit, and EMIAT found no all-cause mortality difference. The evidence points to arrhythmia suppression without a reliable survival gain. Evidence: disputed. (Source 4)
• Cochrane found amiodarone the most effective drug at preventing recurrence (risk ratio 0.52), but with a 6.7-fold rise in withdrawals for adverse effects and no demonstrated benefit on mortality or stroke. In the US this use is not on the tablet label. Evidence: established. (Source 5)
• A meta-analysis of 14 randomised trials in 2,864 patients found amiodarone significantly reduced postoperative atrial fibrillation, with odds ratios between 0.44 and 0.58 depending on total dose. The authors said their dose and timing conclusions require confirmation in prospective trials. Evidence: limited. (Source 6)

Interactions

• Grapefruit juice (pharmacokinetic study): Grapefruit juice blocks the CYP3A enzyme that converts amiodarone to its main metabolite. In eleven healthy volunteers it completely stopped that conversion and raised amiodarone blood exposure by 50% and peak concentration by 84%. The label tells patients to avoid it. (Source 7)
• St John's wort (Hypericum perforatum) (label): St John's wort induces CYP3A and the label lists it as a CYP450 inducer that reduces amiodarone blood levels, which could let the arrhythmia return. The label instructs that patients be told to avoid it. We found no published human pharmacokinetic study of this specific pair. (Source 8)
• Food, especially a high-fat meal (pharmacokinetic study): Taking amiodarone with food markedly increases how much is absorbed. In 30 healthy subjects a single 600 mg dose after a high-fat meal gave 2.3 times the total exposure and 3.8 times the peak concentration seen after an overnight fast, which is why the label says to take it consistently with regard to meals. (Source 9)
• Cholestyramine (a bile-acid binding resin) (label): Cholestyramine interrupts the recirculation of amiodarone through the gut and liver, speeding its removal and lowering blood levels and half-life. (Source 10)

Stopping it

• There is no withdrawal syndrome and no tapering schedule in the literature we searched, but the opposite problem exists: because amiodarone's half-life is 15 to 142 days and its active metabolite's 14 to 75 days, both its effects and its interactions carry on for weeks after the last tablet. (Source 11)
• After chronic oral therapy stops, blood levels fall in two phases: roughly half is gone in 2.5 to 10 days, then a very slow terminal phase with a half-life averaging about 53 days, because the drug leaves poorly perfused tissues such as fat only slowly. (Source 12)
• Some toxicities partly reverse after stopping. The label states corneal microdeposits are reversible on dose reduction or stopping, and that some of the blue-gray skin discoloration may reverse after the drug is discontinued. (Source 13)

What goes wrong

The same meta-analysis found an excess of pulmonary toxicity of 1% per year on amiodarone compared with control. (Source 4)

• Meta-analysis, Moderate certainty.
• Size: 6,553 patients across 13 trials.
• Who: post-myocardial-infarction and congestive heart failure patients.
• How long: pooled trial follow-up.
• Result: excess (amiodarone minus control) risk of pulmonary toxicity 1% per year.
• Funding: not stated.

The excess (amiodarone minus control) risk of pulmonary toxicity was 1% per year.

In the same Cochrane review, amiodarone increased withdrawals for adverse effects nearly sevenfold, on evidence the review itself rated low-certainty. (Source 14)

• Systematic review, Low certainty.
• Size: 59 RCTs, 20,981 participants in the review; amiodarone withdrawal estimate pooled from its amiodarone trials.
• Who: adults who had recovered sinus rhythm after atrial fibrillation (postoperative atrial fibrillation excluded)
• How long: mean follow-up 10.2 months.
• Result: Withdrawals due to adverse effects, amiodarone RR 6.70 (95% CI 1.91 to 23.45); the review rated the certainty of this outcome low for amiodarone.
• Funding: independent (Cochrane review)

All analysed drugs increased withdrawals due to adverse effects compared to placebo or no treatment (quinidine: RR 1.56, 95% CI 0.87 to 2.78; disopyramide: RR 3.68, 95% CI 0.95 to 14.24; propafenone: RR 1.62, 95% CI 1.07 to 2.46; flecainide: RR 15.41, 95% CI 0.91 to 260.19; metoprolol: RR 3.47, 95% CI 1.48 to 8.15; amiodarone: RR 6.70, 95% CI 1.91 to 23.45; dofetilide: RR 1.77, 95% CI 0.75 to 4.18; dronedarone: RR 1.58, 95% CI 1.34 to 1.85; sotalol: RR 1.95, 95% CI 1.23 to 3.11). Certainty of the evidence for this outcome was low for disopyramide, amiodarone, dofetilide and flecainide; moderate to high for the remaining drugs.

Even at daily doses of 400 mg or less, amiodarone significantly raised the odds of thyroid, neurologic, skin, eye and bradycardic adverse effects compared with placebo, and of stopping the drug. (Source 15)

• Meta-analysis, Moderate certainty.
• Size: 1,465 patients in four double-blind placebo-controlled trials (738 amiodarone, 727 placebo)
• Who: adults in placebo-controlled trials with mean amiodarone dose 152 to 330 mg per day.
• How long: mean follow-up at least 12 months.
• Result: thyroid OR 4.2 (95% CI 2.0 to 8.7); neurologic OR 2.0 (1.1 to 3.7); skin OR 2.5 (1.1 to 6.2); ocular OR 3.4 (1.2 to 9.6); bradycardia OR 2.2 (1.1 to 4.3); discontinuation 22.9% amiodarone versus 15.4% placebo, OR 1.52 (1.2 to 1.9), p = 0.003.
• Funding: not stated.

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

In a nationwide Icelandic cohort of everyone starting amiodarone in one year, nearly 40% developed thyroid dysfunction within five years. (Source 16)

• Cohort study, Moderate certainty.
• Size: 262 euthyroid patients who filled a first amiodarone prescription in Iceland in 2014.
• Who: all new amiodarone users in Iceland in 2014, euthyroid at baseline.
• How long: up to 5 years, with death as a competing risk.
• Result: 5-year cumulative incidence: thyrotoxicosis 19.0% (95% CI 11.9-25.5), hypothyroidism 21.8% (14.7-28.2), any thyroid dysfunction 38.5% (30.4-45.7). Complications of thyrotoxicosis included hospitalisation 36%, thyroidectomy 8%, death 4%.
• Funding: not stated.

Limit of this finding: The recorded passage from this paper gives the same peak figure, 9.8%, for two different things - the worst year for amiodarone-induced thyrotoxicosis (the third year of treatment) and the worst year for amiodarone-induced hypothyroidism (the first year). Two different conditions peaking at an identical value is the shape a copying slip takes, and the paper's full text is behind a paywall so it could not be checked against its own tables. Treat the two yearly peaks as unconfirmed. The figures this finding actually rests on - the five-year cumulative incidences of 19.0%, 21.8% and 38.5% - are reported separately and are not affected.

the 5-year cumulative incidence in the same order was 19.0% (95% CI: 11.9%-25.5%), 21.8% (95% CI: 14.7%-28.2%), and 38.5% (95% CI: 30.4%-45.7%)

The FDA label records, as a boxed warning, that clinically manifest pulmonary toxicity has been reported at rates as high as 17% and has been fatal about 10% of the time. (Source 2)

• Official position, Certainty not rated.
• Size: not stated - case series cited in the label.
• Who: patients treated with oral amiodarone.
• How long: not stated.
• Result: pulmonary toxicity rates as high as 17% in some series; fatal in about 10% of cases.
• Funding: regulatory label (manufacturer-authored, FDA-approved), revised 2/2026.

can cause pulmonary toxicity (hypersensitivity pneumonitis or interstitial/alveolar pneumonitis) that has resulted in clinically manifest disease at rates as high as 17% in some series of patients. Pulmonary toxicity has been fatal about 10% of the time.

The label states that amiodarone causes hypothyroidism in up to 10% of patients and hyperthyroidism in about 2%, and that corneal microdeposits appear in the majority of adults treated. (Source 13)

• Official position, Certainty not rated.
• Size: not stated.
• Who: adults treated with oral amiodarone.
• How long: long-term treatment.
• Result: hypothyroidism up to 10%; hyperthyroidism about 2%; corneal microdeposits in the majority, with visual halos or blurred vision in as many as 10%.
• Funding: regulatory label, revised 2/2026.

Amiodarone hydrochloride can cause either hypothyroidism (reported in up to 10% of patients) or hyperthyroidism (occurring in about 2% of patients).

The label states amiodarone causes photosensitisation in about 10% of patients and that a blue-gray discoloration of exposed skin may develop with long-term use. (Source 17)

• Official position, Certainty not rated.
• Size: not stated.
• Who: adults on long-term oral amiodarone.
• How long: long-term treatment.
• Result: photosensitisation in about 10%; blue-gray skin discoloration with long-term treatment, partly reversible on stopping.
• Funding: regulatory label, revised 2/2026.

Amiodarone hydrochloride induces photosensitization in about 10% of patients; some protection may be afforded sun-barrier creams or protective clothing. During long-term treatment, a blue-gray discoloration of the exposed skin may occur.

The label states amiodarone can exacerbate the presenting arrhythmia in about 2 to 5% of patients and can cause life-threatening hepatic injury. (Source 18)

• Official position, Certainty not rated.
• Size: not stated.
• Who: adults treated with oral amiodarone.
• How long: not stated.
• Result: asymptomatic hepatic enzyme elevations frequent; life-threatening hepatic injury possible, histology resembling alcoholic hepatitis or cirrhosis.
• Funding: regulatory label, revised 2/2026.

Asymptomatic elevations of hepatic enzyme levels are seen frequently, but amiodarone hydrochloride can cause life-threatening hepatic injury. Histology has resembled that of alcoholic hepatitis or cirrhosis.

The FDA label lists thyroid, cardiac, gastrointestinal, skin, neurologic, eye, liver and lung reactions as common on amiodarone, but gives only frequency words and no percentages for any of them. (Source 19)

• Official position, Certainty not rated.
• Size: a retrospective study of 241 patients cited in the label.
• Who: patients treated with oral amiodarone for 2 to 1,515 days (mean 441.3 days)
• How long: mean 441.3 days of treatment.
• Result: The label's table gives frequency categories only: nausea and vomiting as 'Very common', and hypothyroidism, hyperthyroidism, congestive heart failure, cardiac arrhythmias, SA node dysfunction, constipation, anorexia, abdominal pain, solar dermatitis/photosensitivity, malaise and fatigue, tremor, ataxia, dizziness, paraesthesias, decreased libido, insomnia, headache, sleep disturbance, visual disturbance, abnormal liver-function tests and pulmonary inflammation or fibrosis as 'Common'. No percentage is attached to any entry.
• Funding: regulatory label (manufacturer-authored, FDA-approved), revised 2/2026.

Limit of this finding: This part of the label is headed 'side-effect rates' but gives no rates. It sorts reactions into 'Very common' and 'Common' without saying what percentage either word stands for, and there was no untreated comparison group, so nothing here tells you how often these problems happen on amiodarone compared with not taking it. For actual percentages, see the placebo-controlled meta-analysis and the Icelandic thyroid cohort recorded separately here.

The following side-effect rates are based on a retrospective study of 241 patients treated for 2 to 1,515 days (mean 441.3 days): Thyroid Common: Hypothyroidism, hyperthyroidism.

What the evidence supports

In a meta-analysis of individual patient data from 13 randomised trials after myocardial infarction or in congestive heart failure, prophylactic amiodarone reduced total mortality by 13% and arrhythmic or sudden death by 29%. (Source 4)

• Meta-analysis, Moderate certainty.
• Size: 6,553 patients randomised across 13 trials (8 post-MI, 5 CHF)
• Who: adults with recent myocardial infarction or congestive heart failure; mean left-ventricular ejection fraction 31%.
• How long: trial follow-up varied; individual patient data pooled.
• Result: Total mortality odds ratio 0.87 (95% CI 0.78-0.99), p = 0.030 fixed-effects; 0.85 (0.71-1.02), p = 0.081 random-effects. Arrhythmic/sudden death 0.71 (0.59-0.85), p = 0.0003. No effect on non-arrhythmic death (1.02, 0.87-1.19, p = 0.84).
• Funding: not stated.

Total mortality was reduced by 13% (odds ratio 0.87 [95% CI 0.78-0.99], p = 0.030) based on classic fixed-effects meta-analysis and by 15% (0.85 [0.71-1.02], p = 0.081) with the more conservative random-effects approach. Arrhythmic/sudden death was reduced by 29% (0.71 [0.59-0.85], p = 0.0003).

In survivors of myocardial infarction with frequent ventricular premature depolarisations, amiodarone cut resuscitated ventricular fibrillation or arrhythmic death from 6.9% to 4.5%. (Source 20)

• Randomized trial, Moderate certainty.
• Size: 1,202 patients (606 amiodarone, 596 placebo)
• Who: myocardial infarction survivors with 10 or more ventricular premature depolarisations per hour or a run of ventricular tachycardia.
• How long: mean follow-up 1.79 years (SD 0.44)
• Result: efficacy analysis 39 (6.9%) placebo versus 25 (4.5%) amiodarone, relative-risk reduction 48.5% (95% CI 4.5 to 72.2), p = 0.016; intention-to-treat 38.2% (95% CI -2.1 to 62.6), p = 0.029 - an absolute difference of about 2.4 percentage points.
• Funding: not stated.

In the efficacy analysis, resuscitated ventricular fibrillation or arrhythmic death occurred in 39 (6.9%) [corrected] patients in the placebo group and in 25 (4.5%) [corrected] in the amiodarone group (relative-risk reduction 48.5% [95% CI 4.5 to 72.2], p = 0.016).

For maintaining sinus rhythm after cardioversion of atrial fibrillation, Cochrane found amiodarone roughly halved the recurrence of atrial fibrillation, on moderate- to high-certainty evidence. (Source 5)

• Systematic review, Moderate certainty.
• Size: 59 randomised trials, 20,981 participants across nine drugs.
• Who: adults who had recovered sinus rhythm after atrial fibrillation (postoperative atrial fibrillation excluded)
• How long: mean follow-up 10.2 months.
• Result: Recurrence of atrial fibrillation with amiodarone: RR 0.52 (95% CI 0.46 to 0.58). Despite the reduction, atrial fibrillation still recurred in 43% to 67% of people treated with antiarrhythmics.
• Funding: independent (Cochrane review)

Moderate- to high-certainty evidence, with the exception of disopyramide which was low-certainty evidence, showed that all analysed drugs, including metoprolol, reduced recurrence of atrial fibrillation

Amiodarone given around cardiac surgery reduced the incidence of postoperative atrial fibrillation. (Source 6)

• Meta-analysis, Low certainty.
• Size: 14 randomised controlled trials, 2,864 patients.
• Who: adults undergoing cardiac surgery.
• How long: postoperative period.
• Result: Pooled across dose bands defined by the paper as low (< 3000 mg), medium (3000-5000 mg) and high (> 5000 mg) total administered amiodarone: low OR 0.58 (95% CI 0.44-0.77), medium OR 0.45 (0.30-0.69), high OR 0.44 (0.33-0.58), with no significant difference between the bands (p=0.238). The authors concluded total doses of 3000 mg or higher may be more effective than lower doses, and that these findings require confirmation in prospective, randomized trials.
• Funding: not stated.

The incidence of postoperative atrial fibrillation was significantly reduced by amiodarone compared with placebo (p<0.001).

What the evidence does not support

In the largest placebo-controlled trial in heart failure, amiodarone did not reduce death from any cause. (Source 21)

• Randomized trial, High certainty.
• Size: 2,521 patients (845 amiodarone, 847 placebo, 829 ICD)
• Who: NYHA class II or III congestive heart failure with left ventricular ejection fraction 35 percent or less.
• How long: median follow-up 45.5 months.
• Result: 244 deaths (29 percent) on placebo versus 240 (28 percent) on amiodarone; hazard ratio 1.06 (97.5% CI 0.86 to 1.30), P=0.53. ICD reduced death by 23% (0.77, 0.62-0.96) with an absolute 7.2 percentage point mortality reduction at five years.
• Funding: not stated in the abstract (publicly funded trial with industry drug supply)

As compared with placebo, amiodarone was associated with a similar risk of death (hazard ratio, 1.06; 97.5 percent confidence interval, 0.86 to 1.30; P=0.53)

The Cochrane review found that antiarrhythmic drugs reduce atrial fibrillation recurrence but with no demonstrated benefit on other clinical outcomes compared with placebo or no treatment. (Source 5)

• Systematic review, Moderate certainty.
• Size: 59 RCTs, 20,981 participants.
• Who: adults in sinus rhythm after atrial fibrillation.
• How long: mean 10.2 months.
• Result: no evidence of benefit on clinical outcomes other than recurrence; adverse and proarrhythmic events increased across the drug class.
• Funding: independent (Cochrane review)

Conversely, although they reduce recurrences of atrial fibrillation, there is no evidence of any benefit on other clinical outcomes, compared with placebo or no treatment.

In out-of-hospital cardiac arrest with shock-refractory ventricular fibrillation, amiodarone did not significantly improve survival to hospital discharge compared with placebo. (Source 3)

• Randomized trial, High certainty.
• Size: 3,026 patients in the per-protocol population (974 amiodarone, 993 lidocaine, 1,059 placebo)
• Who: adults with non-traumatic out-of-hospital cardiac arrest and shock-refractory ventricular fibrillation or pulseless ventricular tachycardia.
• How long: to hospital discharge.
• Result: survival to discharge 24.4% amiodarone versus 21.0% placebo; difference 3.2 percentage points (95% CI -0.4 to 7.0; P=0.08). More amiodarone recipients required temporary cardiac pacing.
• Funding: Funded by the National Heart, Lung, and Blood Institute and others.

The difference in survival rate for amiodarone versus placebo was 3.2 percentage points (95% confidence interval [CI], -0.4 to 7.0; P=0.08)

In the same meta-analysis, hepatic and gastrointestinal adverse effects at low dose were no more common than on placebo, and the increase in pulmonary toxicity did not reach statistical significance. (Source 15)

• Meta-analysis, Moderate certainty.
• Size: 1,465 patients in four trials.
• Who: adults on 400 mg per day or less.
• How long: at least 12 months.
• Result: hepatic and gastrointestinal odds similar to placebo; pulmonary toxicity OR 2.0 (95% CI 0.9 to 5.3), p = 0.07.
• Funding: not stated.

resulted in odds similar to those of placebo for hepatic and gastrointestinal adverse effects

Where the evidence is mixed

In survivors of myocardial infarction with ejection fraction 40% or less, amiodarone did not reduce all-cause or cardiac mortality, though arrhythmic deaths fell. (Source 22)

• Randomized trial, High certainty.
• Size: 1,486 patients (743 amiodarone, 743 placebo)
• Who: survivors of myocardial infarction with left-ventricular ejection fraction 40% or less.
• How long: median follow-up 21 months.
• Result: 103 deaths on amiodarone versus 102 on placebo; 35% risk reduction in arrhythmic deaths (95% CI 0-58, p = 0.05)
• Funding: not stated.

All-cause mortality (103 deaths in the amiodarone group, 102 in the placebo group) and cardiac mortality did not differ between the two groups. However, in the amiodarone group, there was a 35% risk reduction (95% CI 0-58, p = 0.05) in arrhythmic deaths.

The same review's all-cause mortality estimate for amiodarone came from two small trials and was too imprecise to show either benefit or harm. (Source 14)

• Systematic review, Moderate certainty.
• Size: 2 RCTs, 444 participants, within a review of 59 RCTs and 20,981 participants.
• Who: adults who had recovered sinus rhythm after atrial fibrillation.
• How long: mean follow-up 10.2 months.
• Result: All-cause mortality RR 1.66 (95% CI 0.55 to 4.99), which the review describes as an increased risk ratio with very wide confidence intervals.
• Funding: independent (Cochrane review)

Limit of this finding: This mortality number does not show that amiodarone causes deaths. The range around it runs from 0.55 to 4.99 - that is, from roughly half the death rate seen on placebo to about five times it - so the result is equally consistent with fewer deaths, no difference, or many more. It rests on two trials and 444 people in total. Read it as too uncertain to judge, not as evidence of harm.

Moderate-certainty evidence showed increased RR for mortality but with very wide CIs for metoprolol (RR 2.02, 95% CI 0.37 to 11.05, 2 RCTs, participants = 562) and amiodarone (RR 1.66, 95% CI 0.55 to 4.99, 2 RCTs, participants = 444), compared with placebo.

Where the research disagrees

Whether amiodarone reduces mortality in people at high risk of sudden death

• Amiodarone Trials Meta-Analysis Investigators (1997), meta-analysis of individual patient data from 13 randomised trials, 6,553 patients: Prophylactic amiodarone reduces the rate of arrhythmic/sudden death in high-risk patients with recent MI or CHF and this effect results in an overall reduction of 13% in total mortality. (Source 4)
• SCD-HeFT investigators (2005), randomised double-blind placebo-controlled trial, 2,521 patients, median 45.5 months: In patients with NYHA class II or III CHF and LVEF of 35 percent or less, amiodarone has no favorable effect on survival (Source 21)

How much

• Reference intake: Dosing is set by the prescriber, not by the reader. As a position, the FDA label (revised 2/2026) gives a loading dose of 800 to 1600 mg/day until initial response (usually 1 to 3 weeks), then 600 to 800 mg/day for a month, then a maintenance dose usually of 400 mg/day. (Source 23)
• Upper limit: No tolerable upper intake level exists for a prescription antiarrhythmic. The label's highest stated dose is the 1600 mg/day loading range, and it directs that doses of 1000 mg/day or more be divided and given with meals. (Source 23)
• Studied: CAMIAT gave a loading dose of 10 mg/kg daily for 2 weeks, then 300-400 mg daily for 3.5 months, 200-300 mg daily for 4 months, and 200 mg for 5-7 days per week for 16 months. (Source 20)
• Studied: The four placebo-controlled trials pooled in the low-dose adverse-effect meta-analysis used mean amiodarone doses of 152 to 330 mg per day. (Source 15)

A common belief, and what the research shows

The belief: Amiodarone is the safe antiarrhythmic, the one you use when the others are too risky.

What the research shows: It is effective at suppressing arrhythmias, and it is less proarrhythmic than some alternatives, but it is not safe in the ordinary sense. The FDA label opens with the sentence that it is "intended for use only in patients with the indicated life-threatening arrhythmias because its use is accompanied by substantial toxicity", and the boxed warning records pulmonary toxicity rates as high as 17%, fatal about 10% of the time. Even at 400 mg a day or less, a meta-analysis of placebo-controlled trials found the odds of thyroid problems multiplied by 4.2 and of eye problems by 3.4, and 22.9% of amiodarone patients stopped the drug versus 15.4% on placebo.

Questions and answers

What is it?

Amiodarone is a prescription antiarrhythmic tablet (and injection) that contains iodine. It is classed as a class III antiarrhythmic but in fact has the electrophysiological actions of all four antiarrhythmic classes. It is very fat-soluble, so it builds up in fat, lung, liver and other tissues and clears extremely slowly. (Source 1)

What does it do in the body?

It lengthens the electrical recovery time of heart muscle cells by blocking potassium channels, blocks sodium channels at fast heart rates, blocks calcium channels and blunts adrenaline's effect on the heart. The result is slower conduction through the sinus and AV nodes and a longer refractory period, which makes fast abnormal rhythms harder to sustain. (Source 1)

Is it good or bad for you?

It depends entirely on how dangerous the arrhythmia is. For someone with a life-threatening ventricular arrhythmia the trade-off can be worth it; as prevention in people who are not in immediate danger it is not, because the toxicity is real and the survival benefit is disputed. SCD-HeFT, the largest placebo-controlled trial in heart failure, found a hazard ratio for death of 1.06 - no benefit - while a meta-analysis of 13 trials found a 13% reduction in total mortality. Meanwhile even low doses significantly raise thyroid, eye, skin, nerve and bradycardia problems. (Source 15)

How do you get more of it?

Amiodarone is prescription-only; there is no food or supplement source and no way to raise your level outside a prescriber's dosing decision. Two things do raise blood levels for a given dose: taking it with food, which raised exposure 2.3-fold and peak levels 3.8-fold in 30 healthy subjects, and grapefruit juice, which raised exposure by 50%. Neither is a way to self-adjust; both are reasons the label asks for consistency with meals and avoidance of grapefruit. (Source 9)

If it is harmful, what reduces it?

Stopping the drug is the only route, and it is slow. Half the drug in blood goes in 2.5 to 10 days, then a terminal phase with a half-life averaging about 53 days follows as it leaves fat and other poorly perfused tissue. Cholestyramine interrupts the gut-liver recycling of amiodarone and shortens its half-life, which is why it has been used to speed removal. Effects and interactions persist for weeks after the last dose. (Source 10)

Why might someone be low in it or missing it?

This is a medicine, not a nutrient, so no one is 'low' in it. Blood levels can be lower than expected if it is taken fasting rather than with food, if an enzyme inducer such as St John's wort or rifampicin is also being taken, or if cholestyramine is taken alongside it. The label lists St John's wort as a CYP450 inducer that reduces amiodarone serum levels and tells patients to avoid it. (Source 8)

Which whole foods contain it or feed it?

No food contains amiodarone. Food matters only because it changes absorption: a high-fat meal raised total exposure 2.3-fold and peak concentration 3.8-fold in a 30-subject study, and grapefruit juice raised exposure 50% in eleven volunteers by blocking the enzyme that breaks the drug down. One related point is iodine: amiodarone is an iodine-containing molecule and the label lists known hypersensitivity to iodine as a contraindication. (Source 10)

What happens if you do not have it?

What happens without it depends on the arrhythmia. In the placebo arms of the trials, risk was real but not uniform: in CAMIAT, 6.9% of placebo patients had resuscitated ventricular fibrillation or arrhythmic death over about 1.8 years versus 4.5% on amiodarone; in SCD-HeFT, 29% of placebo patients died over a median 45.5 months versus 28% on amiodarone. For maintaining sinus rhythm after atrial fibrillation, without a drug recurrence is common, and even on antiarrhythmics atrial fibrillation still recurred in 43% to 67% of people. (Source 5)

How can you test for it?

There is no useful self-test, and plasma concentration monitoring is not how amiodarone is managed; the label notes considerable inter-subject variation and uncertainty about which body compartment matters for the drug's effect. What is monitored is its toxicity: baseline and periodic liver transaminases, thyroid function tests, chest X-ray and pulmonary function tests including diffusion capacity, and slit-lamp eye examination. The Icelandic cohort suggests thyroid testing matters most in the first and third treatment years. (Source 16)

References

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2. DailyMed, U.S. National Library of Medicine (label of Aurobindo Pharma USA, repackaged by RemedyRepack Inc.). AMIODARONE HYDROCHLORIDE TABLET - FDA prescribing information (SPL), revised 2/2026 - Boxed Warning. 2026. Read the source
3. The New England journal of medicine. Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest.. 2016. PMID 27043165, DOI 10.1056/nejmoa1514204. Read the source
4. Lancet (London, England). Effect of prophylactic amiodarone on mortality after acute myocardial infarction and in congestive heart failure: meta-analysis of individual data from 6500 patients in randomised trials. Amiodarone Trials Meta-Analysis Investigators.. 1997. PMID 9371164. Read the source
5. The Cochrane database of systematic reviews. Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation. - Main results: recurrence of atrial fibrillation; Authors' conclusions. 2019. PMID 31483500, DOI 10.1002/14651858.cd005049.pub5. Read the source
6. Pharmacotherapy. Amiodarone prophylaxis for atrial fibrillation after cardiac surgery: meta-analysis of dose response and timing of initiation.. 2007. PMID 17316148, DOI 10.1592/phco.27.3.360. Read the source
7. British journal of clinical pharmacology. Dramatic inhibition of amiodarone metabolism induced by grapefruit juice.. 2000. PMID 10759694, DOI 10.1046/j.1365-2125.2000.00163.x. Read the source
8. DailyMed, U.S. National Library of Medicine (label of Aurobindo Pharma USA, repackaged by RemedyRepack Inc.). AMIODARONE HYDROCHLORIDE TABLET - FDA prescribing information (SPL), revised 2/2026 - Patient Counseling Information 17. 2026. Read the source
9. DailyMed, U.S. National Library of Medicine (label of Aurobindo Pharma USA, repackaged by RemedyRepack Inc.). AMIODARONE HYDROCHLORIDE TABLET - FDA prescribing information (SPL), revised 2/2026 - Clinical Pharmacology 12.3, Absorption. 2026. Read the source
10. DailyMed, U.S. National Library of Medicine (label of Aurobindo Pharma USA, repackaged by RemedyRepack Inc.). AMIODARONE HYDROCHLORIDE TABLET - FDA prescribing information (SPL), revised 2/2026 - Clinical Pharmacology 12.3, Drug Interactions. 2026. Read the source
11. DailyMed, U.S. National Library of Medicine (label of Aurobindo Pharma USA, repackaged by RemedyRepack Inc.). AMIODARONE HYDROCHLORIDE TABLET - FDA prescribing information (SPL), revised 2/2026 - Warnings and Precautions 5.1-5.2. 2026. Read the source
12. DailyMed, U.S. National Library of Medicine (label of Aurobindo Pharma USA, repackaged by RemedyRepack Inc.). AMIODARONE HYDROCHLORIDE TABLET - FDA prescribing information (SPL), revised 2/2026 - Clinical Pharmacology 12.3, Elimination. 2026. Read the source
13. DailyMed, U.S. National Library of Medicine (label of Aurobindo Pharma USA, repackaged by RemedyRepack Inc.). AMIODARONE HYDROCHLORIDE TABLET - FDA prescribing information (SPL), revised 2/2026 - Warnings and Precautions 5.5-5.6. 2026. Read the source
14. The Cochrane database of systematic reviews. Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation. - Main results: all-cause mortality and withdrawals due to adverse events. 2019. PMID 31483500, DOI 10.1002/14651858.cd005049.pub5. Read the source
15. Journal of the American College of Cardiology. Adverse effects of low dose amiodarone: a meta-analysis.. 1997. PMID 9283542, DOI 10.1016/s0735-1097(97)00220-9. Read the source
16. Journal of internal medicine. Amiodarone induced thyroid dysfunction: A high cumulative incidence in a nationwide cohort study in Iceland.. 2025. PMID 40637127, DOI 10.1111/joim.20115. Read the source
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18. DailyMed, U.S. National Library of Medicine (label of Aurobindo Pharma USA, repackaged by RemedyRepack Inc.). AMIODARONE HYDROCHLORIDE TABLET - FDA prescribing information (SPL), revised 2/2026 - Warnings and Precautions 5.3-5.4. 2026. Read the source
19. DailyMed, U.S. National Library of Medicine (label of Aurobindo Pharma USA, repackaged by RemedyRepack Inc.). AMIODARONE HYDROCHLORIDE TABLET - FDA prescribing information (SPL), revised 2/2026 - Adverse Reactions 6.1. 2026. Read the source
20. Lancet (London, England). Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators.. 1997. PMID 9078198, DOI 10.1016/s0140-6736(96)08171-8. Read the source
21. The New England journal of medicine. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure.. 2005. PMID 15659722, DOI 10.1056/nejmoa043399. Read the source
22. Lancet (London, England). Randomised trial of effect of amiodarone on mortality in patients with left-ventricular dysfunction after recent myocardial infarction: EMIAT. European Myocardial Infarct Amiodarone Trial Investigators.. 1997. PMID 9078197, DOI 10.1016/s0140-6736(96)09145-3. Read the source
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