What are the side effects of Amiodarone?

From the Guidelines

Amiodarone has numerous side effects, including bradycardia, QT prolongation, torsades de pointes, 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 2015 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:

• Cardiovascular effects: bradycardia, QT prolongation, torsades de pointes
• Gastrointestinal effects: gastrointestinal upset, constipation
• Endocrine effects: hypothyroidism, hyperthyroidism
• Pulmonary effects: pulmonary fibrosis, adult respiratory distress syndrome
• Hepatic effects: hepatic toxicity
• Ocular effects: corneal deposits, optic neuritis
• Neurological effects: peripheral neuropathy, photosensitivity It is essential to monitor patients on amiodarone regularly for these potential side effects, as they can have a significant impact on morbidity, mortality, and quality of life. According to a more recent study published in 2022, amiodarone can also cause gastrointestinal, ocular, hyper/hypothyroidism, pulmonary fibrosis, cutaneous, neurological, hepatic, renal impairment, and muscle weakness 1. The maintenance dose of amiodarone should be maximized at 200 mg/day to minimize long-term adverse effects, as recommended by the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy 1. Regular monitoring of the ECG, BP, and serum K+ and Mg2+ is crucial for patients on amiodarone, and doses should be individualized according to the QTc interval, renal function, and serum K+ and Mg2+. Patients should be advised to report any new symptoms promptly to their healthcare provider, and regular monitoring of thyroid, liver, lung, and eye function is necessary to minimize the risk of adverse effects.

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, cardiac arrest, cardiogenic shock, congestive heart failure, bradycardia, AV block, VT
• Hepatic: liver function test abnormalities
• Respiratory: lung edema, respiratory disorder, fatal respiratory disorders
• Hematologic: thrombocytopenia, hemolytic anemia, aplastic anemia, pancytopenia, neutropenia, agranulocytosis
• Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, skin cancer, vasculitis, pruritus
• Neurologic: hallucination, confusional state, disorientation, delirium
• Gastrointestinal: diarrhea, vomiting
• Renal: abnormal kidney function
• Endocrine: thyroid nodules/thyroid cancer, syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• Musculoskeletal: myopathy, muscle weakness, rhabdomyolysis
• Other: fever, dyspnea, cough, hemoptysis, wheezing, hypoxia, pulmonary infiltrates and/or mass, pleuritis, pseudotumor cerebri, epididymitis, 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:

• Gastrointestinal side effects, such as constipation, which occurred in 56 patients in a study published in the Journal of the American College of Cardiology 3
• Corneal microdeposits, which developed in all but one patient in the same study 3
• Neurologic side effects, including tremor and ataxia, which occurred in 52 patients 3
• Thyroid dysfunction, which occurred in 3 patients 3
• Cutaneous abnormalities, which occurred in 32 patients 3
• Pulmonary side effects, including symptomatic pulmonary toxicity, which occurred in 7 patients 3

Organ-Specific Side Effects

Amiodarone can cause side effects in various organs, including:

• Thyroid gland: Amiodarone can cause thyroid abnormalities, including hyperthyroidism and hypothyroidism, as reported in a study published in Wiener klinische Wochenschrift 4
• Liver: Amiodarone can cause hepatotoxicity, although no cases were reported in the study published in Wiener klinische Wochenschrift 4
• Lungs: Amiodarone can cause pulmonary fibrosis, as reported in a study published in American journal of cardiovascular drugs : drugs, devices, and other interventions 5
• Skin: Amiodarone can cause phototoxicity and hyperpigmentation, as reported in the study published in Wiener klinische Wochenschrift 4

Management of Side Effects

To minimize the risk of side effects, it is essential to:

• Use the lowest effective dosage of Amiodarone, as suggested in a study published in Progress in cardiovascular diseases 6
• Monitor patients regularly for signs of toxicity, as recommended in the study published in American heart journal 7
• Reduce the dosage or discontinue the medication if severe side effects occur, as reported in the study published in Journal of the American College of Cardiology 3