Amiodarone


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 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 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, ventricular tachycardia, 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 recent study suggested that another antiarrhythmic, procainamide, may be more effective in stopping ventricular tachycardia – with less side effects and a higher survival rate in patients requiring multiple shocks. However, due to a small sample size and lack of statistical significance, more evidence is required, and amiodarone remains the drug of choice in ventricular arrhythmias.
Amiodarone is also commonly used as the first-line therapy for patients who receive shocks from implantable cardioverter defibrillators caused by ventricular arrhythmias. Combining amiodarone with beta-blockers has been shown to reduce the likelihood of experiencing inappropriate shocks from implantable cardioverter defibrillators.

Cardiac arrest

is the treatment of choice for ventricular fibrillation and pulseless ventricular tachycardia resulting in cardiac arrest. While amiodarone has been used in shock-refractory cases, evidence of benefit is poor. 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 in the first few days post-procedure. In the ARCH trial, intravenous amiodarone 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, 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 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. However, other anti-arrhythmic agents may exert superior rhythm control, rate control and lower mortality rate which may be more favourable 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:
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

At oral doses of 400 mg per day or higher, amiodarone can have serious, varied side effects, including toxicity to the thyroid gland, liver, lung, and retinal functions, requiring clinical surveillance and regular laboratory testing. 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 ;
  • 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 ;
  • thyroid dysfunction ;
  • pulmonary toxicity ;
  • liver abnormalities ;
  • bradycardia and 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

Induced abnormalities in thyroid function are common. In approximately 15-20% of patients, amiodarone treatment results in thyroid dysfunction, either amiodarone-induced hypothyroidism or amiodarone-induced thyrotoxicosis. Both under- and overactivity of the thyroid may occur.
Amiodarone is structurally similar to thyroxine and also contains iodine. Both of these factors contribute to the effects of amiodarone on thyroid function. Amiodarone also causes an anti-thyroid action, via Plummer and Wolff–Chaikoff effects, due its large amount of iodine in its molecule, which causes a particular "cardiac hypothyroidism" with bradycardia and arrhythmia.
Thyroid function should be checked at least every six months.
  • Hypothyroidism occurs frequently; in the SAFE trial, which compared amiodarone with other medications for the treatment of atrial fibrillation, biochemical hypothyroidism occurred in 25.8% of the amiodarone-treated group as opposed to 6.6% of the control group. Overt hypothyroidism occurred at 5.0% compared to 0.3%; most of these were detected within the first six months of amiodarone treatment.
  • Amiodarone induced thyrotoxicosis, can be caused due to the high iodine content in the drug via the Jod-Basedow effect. This is known as Type 1 AIT, and usually occurs in patients with an underlying predisposition to hyperthyroidism such as Graves' disease, within weeks to months after starting amiodarone. Type 1 AIT is usually treated with anti-thyroid drugs or thyroidectomy. Type 2 AIT is caused by a destructive thyroiditis due to a direct toxic effect of amiodarone on thyroid follicular epithelial cells. Type 2 AIT can occur even years after starting amiodarone, is usually self-limited and responds to anti-inflammatory treatment such as corticosteroids. In practice, often the type of AIT is undetermined or presumed as mixed with both treatments combined. Thyroid uptake measurements, which are used to differentiate causes of hyperthyroidism, are generally unreliable in patients who have been taking amiodarone. Because of the high iodine content of amiodarone, the thyroid gland is effectively saturated, thus preventing further uptake of isotopes of iodine. However, positive radioactive iodine can be used to rule in type 1AIT.