What are the absolute and relative contraindications to amiodarone?

Contraindications of Amiodarone

Absolute Contraindications

Amiodarone is absolutely contraindicated in patients with cardiogenic shock, marked sinus bradycardia, and second- or third-degree AV block unless a functioning pacemaker is in place. 1

Additional absolute contraindications include:

• Known hypersensitivity to amiodarone or any of its components, including iodine 1
• Severe sinus node dysfunction without a pacemaker 2
• Heart transplant patients should not receive amiodarone 2

Relative Contraindications and High-Risk Situations

Cardiovascular Conditions Requiring Extreme Caution

• Baseline bradycardia (heart rate <60 bpm) represents a relative contraindication; amiodarone should only be used if the arrhythmia is immediately life-threatening and no safer alternatives exist 2, 3
• Systolic blood pressure <100 mmHg increases risk of further hemodynamic compromise during therapy 2, 3
• Moderate or severe left ventricular dysfunction or heart failure requires careful consideration, though amiodarone may be safer than class I agents in this population 2, 3
• Pre-excitation syndromes (e.g., Wolff-Parkinson-White) with atrial fibrillation - IV amiodarone can accelerate ventricular response and potentially trigger ventricular fibrillation 2

Pulmonary Considerations

• Pre-existing pulmonary disease or inflammatory lung disease significantly increases the risk of potentially fatal pulmonary toxicity 2, 4
• Severe chronic obstructive pulmonary disease warrants caution 2

Hepatic and Metabolic Concerns

• Severe hepatic dysfunction increases toxicity risk; discontinue if liver enzymes exceed three times normal unless the patient faces life-threatening arrhythmia recurrence 2
• Insulin-dependent diabetes requires additional monitoring 2

QT Interval and Proarrhythmic Risk

• Prolonged QT interval - While amiodarone commonly prolongs QT, it has lower torsades de pointes risk than pure potassium channel blockers 2
• QTc >500 ms should prompt dose reduction or discontinuation 2
• Concomitant use with other QT-prolonging medications (procainamide, sotalol) requires expert consultation 2
• Risk factors that amplify concern: female sex, marked LV hypertrophy, severe bradycardia, renal dysfunction, hypokalemia, or hypomagnesemia 2

Special Populations

• Pregnancy, especially first trimester - amiodarone is category D and should be avoided due to congenital malformation risk 2, 5
• Breastfeeding women - contraindicated 5
• Elderly patients (≥75 years) require heightened vigilance for adverse effects 4

Critical Drug Interactions

• Warfarin: Reduce dose by 33-50% when starting amiodarone and monitor INR weekly for 6 weeks 2, 3
• Digoxin: Reduce dose by 50% as amiodarone predictably doubles digoxin levels 2, 3
• Statins: Increased risk of myopathy and rhabdomyolysis 2
• Beta-blockers, calcium channel blockers: Additive bradycardic and hypotensive effects 3
• Grapefruit juice: Absolutely avoid as it inhibits CYP3A metabolism and increases plasma levels 3

Administration-Specific Contraindications

Intravenous Formulation

• Peripheral vein administration at concentrations >2 mg/mL causes frequent phlebitis; use central venous catheter whenever possible 2, 3
• Must be diluted in 5% dextrose (D5W) - normal saline or lactated Ringer's causes precipitation 3
• Rapid infusion rates dramatically increase hypotension risk (occurs in 16% of patients) 4

Common Pitfalls to Avoid

• Failing to recognize bradycardia risk: Drug-related bradycardia occurs in 4.9% of IV amiodarone patients regardless of dose 3, 4
• Inadequate monitoring: Continuous ECG monitoring is mandatory during IV administration; measure baseline and serial QTc, PR interval, and QRS duration 2, 3
• Overlooking electrolyte abnormalities: Correct hypokalemia and hypomagnesemia before initiating therapy to minimize torsades risk 2
• Ignoring the long half-life: With an average half-life of 58 days (range 15-100 days), drug interactions and adverse effects persist long after discontinuation 3, 6
• Using in permanent atrial fibrillation for rate control: Dronedarone (related compound) increases stroke, MI, and cardiovascular death risk in this setting 2