Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia, ventricular fibrillation, and wide complex tachycardia, atrial fibrillation, and paroxysmal supraventricular tachycardia. Evidence of benefit for cardiac arrest is poor. It can be given by mouth, intravenously, or intraosseously. When used by mouth, it can take a few weeks for effects to begin.
Common side effects include feeling tired, tremor, nausea, and constipation. As amiodarone can have serious side effects, it is mainly recommended only for significant ventricular arrhythmias. Serious side effects include lung toxicity such as interstitial pneumonitis, liver problems, heart arrhythmias, vision problems, thyroid problems, and death. If taken during pregnancy or breastfeeding it can cause problems in the fetus or the infant. It is a class III antiarrhythmic medication. It works partly by increasing the time before a heart cell can contract again.
Amiodarone was first made in 1961 and came into medical use in 1962 for chest pain believed to be related to the heart. It was pulled from the market in 1967 due to side effects. In 1974 it was found to be useful for arrhythmias and reintroduced. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2023, it was the 218th most commonly prescribed medication in the United States, with more than 1million prescriptions.
Medical uses Amiodarone has been used both in the treatment of acute life-threatening arrhythmias as well as the long-term suppression of arrhythmias. Amiodarone is commonly used to treat different types of abnormal heart rhythms, such as atrial arrhythmias (supraventricular arrhythmias) and ventricular arrhythmias.
Atrial arrhythmias and supraventricular arrhythmias are terms often used interchangeably to refer to abnormal heart rhythms originating from the upper chambers of the heart, known as the atria. These types of arrhythmias include conditions such as atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia. They are collectively referred to as supraventricular or atrial arrhythmias because they occur above (supra) the ventricles in the electrical conduction system of the heart.
Ventricular arrhythmias are abnormal heart rhythms that originate in the ventricles, which are the lower chambers of the heart. These arrhythmias can be potentially life-threatening and may disrupt the heart's ability to pump blood effectively.
Amiodarone can be effective in treating conditions like ventricular fibrillation (a rapid and irregular heartbeat), ventricular tachycardia (fast heartbeat originating from the lower chambers), and cardiac arrest due to shock-resistant ventricular fibrillation.
In cases where a patient is experiencing shock-resistant ventricular arrhythmias including stable ventricular tachycardia or unstable ventricular fibrillation, amiodarone may be used. A 2017 randomized study suggests that procainamide may be more effective than amiodarone in terminating ventricular tachycardia and may be associated with fewer short-term adverse effects. However, there is no strong evidence of improved survival, and data in patients requiring multiple shocks are limited, with amiodarone remaining the preferred treatment in this setting.
While early trial data showed that amiodarone plus beta-blockers significantly reduces ICD shocks, recent evidence suggests this combination lacks a consistent survival advantage and may not be more effective than beta-blocker monotherapy in general practice. Amiodarone is also linked to increased mortality and serious toxicities, such as thyroid and pulmonary issues. Therefore, routine use is not recommended; treatment must be individualized by weighing shock reduction against significant safety and survival risks.
Cardiac arrest Defibrillation is the treatment of choice for ventricular fibrillation and pulseless ventricular tachycardia resulting in cardiac arrest. Current evidence does not show a clear benefit of amiodarone on survival or neurological outcomes in cardiac arrest, and its effectiveness remains uncertain due to limitations in the available data.
Although amiodarone does not appear to improve survival in those who had a cardiac arrest in-hospital, some studies suggested that early administration of amiodarone was associated with better survival and positive outcomes for people who had a cardiac arrest out-of-hospital.
Ventricular tachycardia Amiodarone may be used in the treatment of ventricular tachycardia in certain instances. Individuals with hemodynamically unstable ventricular tachycardia should not initially receive amiodarone. These individuals should be cardioverted.
Amiodarone can be used in individuals with hemodynamically stable ventricular tachycardia. In these cases, amiodarone can be used regardless of the individual's underlying heart function and the type of ventricular tachycardia; it can be used in individuals with monomorphic ventricular tachycardia, but is contraindicated in individuals with polymorphic ventricular tachycardia as it is associated with a prolonged QT interval which will be made worse with anti-arrhythmic drugs.
Atrial fibrillation Individuals who have undergone open heart surgery are at an increased risk of developing atrial fibrillation (or AF) in the first few days post-procedure. In the ARCH trial, intravenous amiodarone (2 g administered over 2 d) has been shown to reduce the incidence of atrial fibrillation after open heart surgery when compared to placebo. However, clinical studies have failed to demonstrate long-term efficacy and have shown potentially fatal side effects such as pulmonary toxicities. While amiodarone is not approved for AF by the US Food and Drug Administration (FDA), it is a commonly prescribed off-label treatment due to the lack of equally effective treatment alternatives.
So-called 'acute onset atrial fibrillation', defined by the North American Society of Pacing and Electrophysiology (NASPE) in 2003, responds well to short-duration treatment with amiodarone. This has been demonstrated in seventeen randomized controlled trials, of which five included a placebo arm. The incidence of severe side effects in this group is low.
Amiodarone is an effective, antiarrhythmic-of-choice in achieving cardioversion to sinus rhythm in critical care populations with new onset atrial fibrillation (NOAF). However, other anti-arrhythmic agents may exert superior rhythm control, rate control and lower mortality rate which may be more favorable than amiodarone in specific cases.
Contraindications Women who are pregnant or may become pregnant are strongly advised not to take amiodarone. Since amiodarone can be expressed in breast milk, women taking the drug are advised to stop nursing.
It is contraindicated in individuals with sinus nodal bradycardia, atrioventricular block, and second or third-degree heart block who do not have an artificial pacemaker.
Individuals with baseline depressed lung function should be monitored closely if amiodarone therapy is to be initiated.
Formulations of amiodarone that contain benzyl alcohol should not be given to neonates, because the benzyl alcohol may cause the potentially fatal "gasping syndrome".
Amiodarone can worsen the cardiac arrhythmia brought on by digitalis toxicity.
Contraindications of amiodarone also include: hypersensitivity to amiodarone or any of its components; severe hepatic impairment; sinus node dysfunction, including severe sinus bradycardia or sinoatrial block, since amiodarone can cause significant bradycardia and sinus nodal arrest; second- or third-degree atrioventricular (AV) block, due to its negative chronotropic (affecting the heart rate) and dromotropic (affecting the conductivity) effects on the AV conduction system, unless a pacemaker is implanted; thyrotoxicosis that cannot be controlled by conventional means, such as Graves' disease.
There are no specific guidelines for endurance or high-intensity exercise while taking amiodarone. However, since amiodarone may cause bradycardia and QTc prolongation which can affect exercise capacity and increase the risk of arrhythmias during intense exercise, it would generally be advisable for patients taking this medication to consult their healthcare provider before engaging in high-intensity physical activities such as strenuous endurance exercises.
Side effects Amiodarone is a medication that takes time to build up in the body before it starts working properly. For this reason, patients are usually started on a higher and more frequent dosage for a short period (eg 1 to 2 weeks), followed by a lower daily maintenance dose. Adverse effects may not manifest until the maintenance stage is reached.
At a lower daily dose (<400mg daily), especially with long-term use. Amiodarone may have adverse effect include thyroid problems, vision changes, nerve-related symptoms (such as tingling or unsteadiness), skin reactions, and a slow heart rate.Higher daily dose (>400mg daily) and longer duration of use is associated with more pulmonary toxicity. The overall exposure to amiodarone over time is an important factor in adverse effects. Therefore, regular blood tests and ongoing check-ups with a GP or Cardiologist are important to monitor for side effects while taking amiodarone.
Allergic reactions to amiodarone may occur. Most individuals administered amiodarone on a chronic basis will experience at least one side effect. In some people, daily use of amiodarone at 100 mg oral doses can be effective for arrhythmia control with no or minimal side effects.
Some common side effects include: nausea and vomiting; taste disturbances (changes in taste perception, often described as a metallic or bitter taste in the mouth); photosensitivity of the skin, also known as photodermatitis, where exposure to sunlight or ultraviolet radiation may lead to skin reactions such as rashes or sunburn-like symptoms; corneal microdeposits (deposits may accumulate on the cornea over time, resulting in blurred vision or visual halosbright circles or rings around a light source, such as headlights; still, these corneal deposits typically do not affect vision significantly); thyroid dysfunction (in approximately 15-20% of patients, amiodarone treatment results in thyroid dysfunction, either amiodarone-induced hypothyroidism or amiodarone-induced thyrotoxicosis; the drug can lead to both hypo- and hyperthyroidism); pulmonary toxicity (lung problems such as pulmonary fibrosis or interstitial lung disease may occur rarely but have the potential for serious consequences if left untreated); liver abnormalities (liver damage, including elevated liver enzymes (AST/ALT) and hepatotoxicity, although severe cases are rare); bradycardia and heart block (since it slows down heart rate by affecting the sinus node function and AV conduction system, it can increase the risk of heart block); QT Interval prolongation.
Amiodarone can potentially cause renal toxicity, but solid studies on whether amiodarone may be toxic to the kidneys are lacking.
Lung
Side effects of oral amiodarone at doses of 400 mg or higher include various pulmonary effects. The most serious reaction is interstitial lung disease. Risk factors include high cumulative dose, more than 400 milligrams per day, duration over two months, increased age, and preexisting pulmonary disease. Some individuals were noted to develop pulmonary fibrosis after a week of treatment, while others did not develop it after years of continuous use. Common practice is to avoid the agent if possible in individuals with decreased lung function.
The most specific test of pulmonary toxicity due to amiodarone is a dramatically decreased DLCO noted on pulmonary function testing.
Thyroid