What are the side effects and monitoring requirements for amiodarone (antiarrhythmic medication)?

Amiodarone Side Effects and Monitoring Requirements

Amiodarone requires rigorous monitoring every six months for thyroid function, liver enzymes, and pulmonary status due to its numerous potentially harmful adverse effects and drug interactions. 1

Major Side Effects

Pulmonary Toxicity

• Pulmonary toxicity is one of the most serious adverse effects, manifesting as interstitial pneumonitis that can be potentially fatal 1, 2
• Baseline chest radiograph and pulmonary function tests should be performed, with follow-up testing if any suspected pulmonary toxicity develops 1, 3
• Symptoms include progressive dyspnea, cough, and sometimes fever 4

Thyroid Dysfunction

• Both hypothyroidism and hyperthyroidism can occur due to amiodarone's high iodine content 1, 3
• Thyroid function tests should be performed at baseline and every six months 1, 3
• Approximately 27% of patients may develop elevated thyroid hormone levels, though clinical hyperthyroidism is less common 5

Hepatic Effects

• Liver enzyme elevations are common and can progress to hepatitis in some cases 1, 2
• Liver transaminase levels should be monitored at baseline and every six months 1, 3
• Consider discontinuation if enzyme levels exceed three times normal, unless the patient is at high risk for life-threatening arrhythmia recurrence 3

Cardiac Effects

• Can cause bradycardia and heart block in 1-3% of patients 3
• Intravenous administration may cause hypotension (16% of patients) and heart block (4.9%) 6
• QT interval prolongation can occur, potentially leading to torsades de pointes 1, 4

Ocular Effects

• Corneal microdeposits develop in virtually all patients on long-term therapy 7
• Visual symptoms occur in approximately 60% of patients 7
• Ophthalmologic examination is recommended if visual symptoms develop 1

Dermatologic Effects

• Photosensitivity occurs in about 31% of patients 5
• Skin hyperpigmentation, especially on sun-exposed areas 7, 5
• Patients should use sun protection and avoid excessive sun exposure 4

Neurological Effects

• Tremor, ataxia, and peripheral neuropathy are common 7
• Neurological side effects occur in approximately 74% of patients on higher doses 7

Gastrointestinal Effects

• Constipation is the most common gastrointestinal side effect 7
• Nausea, vomiting, and anorexia may also occur 4

Monitoring Requirements

Baseline Assessment

• Complete history and physical examination with special attention to heart failure and concomitant medications 1
• Thyroid function tests and liver transaminase levels 1
• Chest radiograph and pulmonary function tests 1
• Eye examination if preexisting visual impairment 1

Follow-up Monitoring

• Every six months:
  • Thyroid function tests and liver transaminase levels 1
  • History and physical examination focused on detecting adverse effects 1
  • Digoxin levels if patient is taking digoxin 1
• Additional monitoring:
  • Chest radiograph and pulmonary function tests if pulmonary toxicity is suspected 1
  • Eye examination if visual symptoms develop 1
  • Prothrombin time/INR at least weekly for the first 6 weeks if taking warfarin 1, 3

Drug Interactions

Warfarin

• Amiodarone reduces warfarin clearance, leading to sudden and pronounced increases in INR 1
• Peak effects of interaction occur approximately 7 weeks after initiation of therapy 1
• Close monitoring of prothrombin time/INR at least weekly during first 6 weeks 1

Digoxin

• Digoxin levels typically double after coadministration with amiodarone 1
• Reduce digoxin dosage by 50% when starting amiodarone 1, 3
• Monitor plasma digoxin levels closely 1

Statins

• Limit simvastatin to 20 mg daily when used with amiodarone due to increased risk of myopathy 3
• Similar caution with other statins metabolized by CYP3A4 4

Other Interactions

• Avoid grapefruit juice as it can inhibit amiodarone metabolism 1
• Caution with beta blockers, calcium channel blockers, and other medications that affect cardiac conduction 4
• Amiodarone inhibits multiple cytochrome P450 pathways (CYP 2C9, CYP 2D6, CYP 3A4) 1

Important Clinical Considerations

• Amiodarone has an unusually long half-life (average 58 days), which can complicate management if adverse effects occur 1, 3
• Side effects are dose-dependent; maintain the lowest effective dose 1, 7
• At maintenance doses of 600 mg daily, virtually all patients develop side effects; lower maintenance doses are recommended 7
• Due to its complex pharmacokinetics and side effect profile, amiodarone should be reserved for patients with refractory arrhythmias or those at high risk 2, 4