Amiodarone Therapy Side Effects and Monitoring

Introduction to Side Effects

Amiodarone has numerous potentially harmful side effects affecting multiple organ systems, with pulmonary toxicity being the most serious adverse effect requiring regular monitoring and prompt intervention 1, 2

The American Academy of Family Physicians notes that pulmonary toxicity is the most serious potential adverse effect of amiodarone therapy, presenting as subacute cough and progressive dyspnea with patchy interstitial infiltrates on chest radiographs 2
Reduced diffusing capacity on pulmonary function tests is a common finding in patients with pulmonary toxicity 2
Any report of worsening dyspnea or cough should prompt immediate assessment 3
Treatment involves withdrawal of amiodarone, supportive care, and sometimes corticosteroids 2
Thyroid dysfunction occurs in 2-24% of patients receiving long-term amiodarone therapy, and can cause both hyperthyroidism and hypothyroidism 2
Regular monitoring of thyroid function tests is mandatory, according to the American Academy of Family Physicians 1
Liver toxicity is manifested by elevation of liver transaminase levels, and occurs at a rate of 0.6% annually 2
If liver enzyme levels exceed three times normal, amiodarone should be discontinued unless patient is at high risk for recurrence of life-threatening arrhythmia 2

Bradycardia and heart block occur in 1-3% of patients, and amiodarone-induced proarrhythmia occurs at an annual rate of <1% 2
QT interval prolongation is common, but torsades de pointes is rare 2
Contraindicated in patients with second- or third-degree heart block without a pacemaker 2
IV administration can cause hypotension (16% of patients) 4

Neurologic toxicity includes ataxia, paresthesias, and tremor, and is often dosage-related 2
Peripheral neuropathy occurs at a rate of 0.3% annually 2
Photosensitivity is common, and patients should use sunblock and cover exposed skin outdoors 2
Corneal microdeposits are visible on slit-lamp examination in nearly all patients, but rarely affect vision or require discontinuation 2
Optic neuropathy and optic neuritis have been reported in rare cases 2

Baseline assessment should include complete history and physical examination, chest radiograph, thyroid studies, liver transaminase levels, and pulmonary function tests 4
Regular monitoring should include thyroid studies and liver transaminase levels every six months, and history and physical examination directed at detecting adverse effects 1, 4

Amiodarone inhibits metabolism of several drugs through cytochrome P450 pathways, and close monitoring of digoxin levels and prothrombin time is necessary 1, 4
Effects of interaction with warfarin and digoxin peak seven weeks after initiation 1
Grapefruit juice can inhibit amiodarone metabolism and lead to elevated drug levels 1

Keep amiodarone dosage at the lowest effective level to minimize side effects, as recommended by the American Academy of Family Physicians 1
The long half-life (average 58 days) means adverse effects may persist after discontinuation 1
Due to high lipid solubility, amiodarone is stored in fat, muscle, liver, lungs, and skin 1