What are the side effects of Amiodarone (antiarrhythmic medication)?

From the Guidelines

Amiodarone can cause numerous side effects, including gastrointestinal upset, constipation, hypothyroidism, hyperthyroidism, pulmonary fibrosis, hepatic toxicity, corneal deposits, optic neuritis, peripheral neuropathy, photosensitivity, and adult respiratory distress syndrome, as reported in the 2016 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia 1. The side effects of amiodarone can be categorized into several groups, including:

• Gastrointestinal effects, such as nausea, vomiting, and constipation
• Thyroid dysfunction, including hypothyroidism and hyperthyroidism, which requires regular monitoring of thyroid function
• Pulmonary toxicity, which can manifest as shortness of breath, cough, or chest pain, and may develop gradually or suddenly
• Hepatic effects, including liver problems and increased risk of hepatic toxicity
• Ocular effects, such as corneal microdeposits and optic neuritis
• Neurological effects, including tremors, coordination problems, and sleep disturbances
• Dermatological effects, such as photosensitivity and skin discoloration (blue-gray) with long-term use According to the 2022 review by the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy, amiodarone can also cause cognitive impairment, and its use should be cautious in patients with structural heart disease or those taking QT-prolonging drugs 1. It is essential to monitor patients taking amiodarone regularly, including their thyroid, liver, lung, and eye function, and to report any new symptoms promptly to their healthcare provider, as recommended in the 2003 guidelines for use and monitoring of amiodarone 1.

From the FDA Drug Label

ADVERSE REACTIONS In a total of 1836 patients in controlled and uncontrolled clinical trials, 14% of patients received amiodarone HCl injection for at least one week, 5% received it for at least 2 weeks, 2% received it for at least 3 weeks, and 1% received it for more than 3 weeks, without an increased incidence of severe adverse reactions. The mean duration of therapy in these studies was 5. 6 days; median exposure was 3. 7 days. The most important treatment-emergent adverse effects were hypotension, asystole/cardiac arrest/ electromechanical dissociation (EMD), cardiogenic shock, congestive heart failure, bradycardia, liver function test abnormalities, VT, and AV block. Overall, treatment was discontinued for about 9% of the patients because of adverse effects The most common adverse effects leading to discontinuation of amiodarone HCl injection therapy were hypotension (1.6%), asystole/cardiac arrest/EMD (1.2%), VT (1. 1%), and cardiogenic shock (1%). The following table lists the most common (incidence ≥ 2%) treatment-emergent adverse events during amiodarone HCl injection therapy considered at least possibly drug-related. Other treatment-emergent possibly drug-related adverse events reported in less than 2% of patients receiving amiodarone HCl injection in controlled and uncontrolled studies included the following: abnormal kidney function, atrial fibrillation, diarrhea, increased ALT, increased AST, lung edema, nodal arrhythmia, prolonged QT interval, respiratory disorder, shock, sinus bradycardia, Stevens-Johnson syndrome, thrombocytopenia, VF, and vomiting (sometimes fatal) (including shock) y fatal respiratory disorders (including distress, failure, arrest, and ARDS), bronchiolitis obliterans organizing pneumonia (possibly fatal), fever, dyspnea, cough, hemoptysis, wheezing, hypoxia, pulmonary infiltrates and/or mass, pleuritis, pseudotumor cerebri, syndrome of inappropriate antidiuretic hormone secretion (SIADH), thyroid nodules/thyroid cancer, toxic epidermal necrolysis (sometimes fatal), erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, skin cancer, vasculitis, pruritus, hemolytic anemia, aplastic anemia, pancytopenia, neutropenia, thrombocytopenia, agranulocytosis, granuloma, myopathy, muscle weakness, rhabdomyolysis, hallucination, confusional state, disorientation, delirium, epididymitis, and impotence also have been reported with amiodarone therapy

The side effects of amiodarone include:

• Cardiovascular: hypotension, asystole, cardiogenic shock, congestive heart failure, bradycardia, AV block, VT
• Hepatic: liver function test abnormalities
• Respiratory: lung edema, respiratory disorder, fatal respiratory disorders
• Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, skin cancer
• Hematologic: thrombocytopenia, hemolytic anemia, aplastic anemia, pancytopenia, neutropenia, agranulocytosis
• Neurologic: hallucination, confusional state, disorientation, delirium
• Other: diarrhea, increased ALT, increased AST, nodal arrhythmia, prolonged QT interval, shock, sinus bradycardia, vomiting, fever, dyspnea, cough, hemoptysis, wheezing, hypoxia, pulmonary infiltrates and/or mass, pleuritis, pseudotumor cerebri, syndrome of inappropriate antidiuretic hormone secretion (SIADH), thyroid nodules/thyroid cancer, vasculitis, pruritus, myopathy, muscle weakness, rhabdomyolysis, epididymitis, and impotence 2

From the Research

Side Effects of Amiodarone

The side effects of amiodarone are numerous and can affect various organ systems. Some of the common side effects include:

• Thyroid abnormalities, such as hypothyroidism and hyperthyroidism 3, 4, 5
• Pulmonary fibrosis and interstitial pulmonary lesions 6, 4
• Transaminitis and liver dysfunction 6, 5
• Corneal deposits and eye changes, such as colored halos and slate-gray skin pigmentation 5
• Neurological abnormalities, such as tremor and sleeplessness 5
• Photosensitivity and skin lesions 5

Serious Side Effects

Some of the serious side effects of amiodarone include:

• Amiodarone-induced thyrotoxicosis (AIT) and hypothyroidism, which can be challenging to diagnose and manage 3
• Pulmonary fibrosis and pneumonitis, which can be life-threatening 4
• Liver dysfunction and hepatitis, which can be severe and require discontinuation of the drug 6, 5

Monitoring and Management

Regular monitoring of patients taking amiodarone is essential to detect potential side effects early on. This includes:

• Routine thyroid function tests to detect thyroid abnormalities 3
• Liver function tests to detect liver dysfunction 6, 5
• Pulmonary function tests to detect pulmonary fibrosis and pneumonitis 4
• Ophthalmologic examinations to detect corneal deposits and eye changes 5
• Neurological examinations to detect neurological abnormalities, such as tremor and sleeplessness 5