What are the potential side effects of amiodarone and how are they managed in patients taking this medication?

Amiodarone Side Effects and Management

Amiodarone causes side effects in virtually all patients, with pulmonary toxicity being the most serious and potentially life-threatening complication, requiring systematic monitoring of thyroid, liver, pulmonary, neurologic, dermatologic, and cardiovascular systems. 1

Most Serious Side Effect: Pulmonary Toxicity

Pulmonary toxicity is the most dangerous adverse effect and can be fatal. 1

• Presents as subacute cough and progressive dyspnea with interstitial infiltrates on chest radiograph and reduced diffusing capacity 1
• Incidence ranges from 1-17%, with more recent data showing approximately 1% annually in patients receiving ≤300 mg daily 1
• Higher maintenance doses (>400 mg/day) increase risk 2
• Any new dyspnea or cough requires immediate evaluation with chest radiograph and pulmonary function tests 3, 1
• Improves with drug withdrawal, with or without corticosteroid treatment 2

Thyroid Dysfunction

Both hypothyroidism (more common) and hyperthyroidism occur due to amiodarone's high iodine content. 1

• Hypothyroidism is 2-4 times more common than hyperthyroidism 1
• Hypothyroid patients can continue amiodarone with thyroid hormone supplementation if clinically indicated 1
• Hyperthyroid patients typically require amiodarone discontinuation 3
• Monitor thyroid studies at baseline and every 6 months 3, 1

Hepatotoxicity

• Manifested primarily by elevated liver transaminase levels 1
• Occurs at approximately 0.6% annually in patients on long-term therapy 1
• Monitor liver function tests at baseline and every 6 months 3, 1
• Hepatotoxicity can occur with overdose 4

Dermatologic Effects

All patients must use broad-spectrum sunblock (SPF ≥30) and cover exposed skin when outdoors. 5

• Photosensitivity occurs in over 50% of patients, presenting as burning, tingling sensation with redness in sun-exposed areas including the face 5
• 1-2% develop distinctive blue-grey or slate-grey pigmentation on sun-exposed sites with continued exposure over months to years 5
• Patients should seek shade, particularly around midday, and remember UV radiation is stronger when reflected by water, sand, or snow 5
• Dosage reduction may help reduce photosensitivity if clinically feasible 5

Neurologic Toxicity

Neurologic effects are dosage-related and improve with dose reduction. 3

• Includes ataxia, paresthesias, and tremor 3, 1
• Peripheral neuropathy occurs at 0.3% annually 3, 1
• Monitor clinically at baseline, during loading, and every 6 months 3

Cardiovascular Adverse Effects

Bradycardia and heart block occur in 1-3% of oral therapy patients and 4.9% with IV administration. 3

• Amiodarone is contraindicated in patients with second- or third-degree heart block without a pacemaker 3
• Proarrhythmia occurs at <1% annually 3
• Although QT prolongation occurs in almost all patients, torsades de pointes is rare 3
• IV amiodarone causes hypotension in 16% of patients 3
• If bradycardia, heart block, or hypotension occur with IV administration, discontinue infusion or reduce rate 3
• Close heart rate surveillance required, especially during first week of treatment 3

Ocular Effects

• Corneal microdeposits develop in virtually all patients on chronic therapy 6
• Ophthalmologic examination recommended at baseline if preexisting visual impairment, and if visual symptoms develop during therapy 3

Critical Drug Interactions

Amiodarone inhibits multiple cytochrome P450 pathways (CYP1A2, CYP2C9, CYP2D6, CYP3A4) and p-glycoprotein, causing numerous clinically significant interactions. 4

Warfarin Interaction (Most Important)

• Increases prothrombin time by 100% after 3-4 days 4
• Reduce warfarin dose by one-third to one-half when starting amiodarone 4
• Monitor PT/INR at least weekly during first 6 weeks 3, 4
• Peak interaction effects occur at approximately 7 weeks 3

Digoxin Interaction

• Digoxin levels predictably double after coadministration 3
• Reduce digoxin dose by approximately 50% or discontinue 4
• Monitor digoxin levels closely and observe for clinical toxicity 3, 4

Statin Interaction

• Simvastatin with amiodarone associated with myopathy/rhabdomyolysis 4

Other Antiarrhythmics

• Reduce quinidine and procainamide doses by one-third 4
• Adjust flecainide dosage when coadministered 4
• Increases phenytoin levels 4

Beta-Blockers and Calcium Channel Blockers

• Use with caution due to possible potentiation of bradycardia, sinus arrest, and AV block 4
• May require pacemaker insertion if severe bradycardia develops 4

Comprehensive Monitoring Protocol

Baseline Assessment 3, 1

• Complete history and physical examination (focus on heart failure, arrhythmia symptoms, concomitant medications)
• Chest radiograph
• Thyroid studies and liver transaminase levels
• Pulmonary function tests including DLCO
• Digoxin level, PT/INR when appropriate
• Ophthalmologic examination if preexisting visual impairment

During Outpatient Loading 3

• Close heart rate surveillance, especially during first week
• History and physical examination for anticipated adverse effects

Every 6 Months 3, 1

• Thyroid studies and liver transaminase levels
• Digoxin level as appropriate
• History and physical examination for adverse effects
• Chest radiograph and pulmonary function tests if suspected pulmonary toxicity
• Ophthalmologic examination if visual symptoms develop

Special Monitoring Situations 3

• PT/INR at least weekly during first 6 weeks of warfarin cotherapy
• Digoxin level if toxicity suspected

Common Pitfalls to Avoid

• Do not use maintenance doses >400 mg/day routinely, as this increases pulmonary toxicity risk 2
• Do not dismiss dermatologic symptoms as trivial—they occur alongside other serious adverse effects 5
• Do not forget that amiodarone effects persist for weeks to months after discontinuation due to long half-life 7
• Do not administer IV amiodarone to patients with bradycardia or heart block without a pacemaker 3
• Do not overlook drug interactions—review all concomitant medications before initiating therapy 4