What is the appropriate loading regimen for amiodarone (intravenous and oral) for acute arrhythmia and elective rhythm control?

Amiodarone Loading Regimens

Intravenous Loading for Acute Arrhythmias

For life-threatening ventricular arrhythmias requiring immediate treatment, administer 150 mg IV over 10 minutes, followed by 1 mg/min for 6 hours (360 mg), then 0.5 mg/min for 18 hours (540 mg), with a maximum total dose of 2.2 g over 24 hours. 1, 2, 3

Acute IV Protocol Details

• Initial bolus: 150 mg in 100 mL D5W infused over 10 minutes 1, 2, 3
• Early maintenance: 1 mg/min for 6 hours (delivers 360 mg) 1, 2, 3
• Late maintenance: 0.5 mg/min for 18 hours (delivers 540 mg) 1, 2, 3
• Breakthrough episodes: Repeat the 150 mg bolus for recurrent VF or hemodynamically unstable VT 3

Administration Requirements

• Must use a volumetric infusion pump, not drop counters (which can underdose by up to 30%) 4
• Administer through a central venous catheter whenever possible 4
• Use an in-line filter during administration 4
• For infusions >1 hour, concentrations should not exceed 2 mg/mL unless using a central line (peripheral concentrations >3 mg/mL cause high rates of phlebitis) 4
• Infusions >2 hours must be in glass or polyolefin bottles, not evacuated glass containers 4

Critical Monitoring During IV Administration

• Continuous cardiac monitoring for hypotension (occurs in 16% of patients), bradycardia, and AV block 1, 2
• Blood pressure monitoring with readiness to slow infusion or add vasopressors if hypotension develops 1, 3
• Daily ECG to assess QT interval and detect heart block 5
• Caution: Patients with ejection fraction <0.35 can experience a 20% decrease in cardiac index with IV bolus administration 6

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Oral Loading for Elective Rhythm Control

For elective rhythm control, initiate oral amiodarone at 600-800 mg daily in divided doses (e.g., 300 mg twice daily) until a cumulative dose of approximately 10 grams is reached, typically requiring 1-2 weeks, then reduce to maintenance dosing of 200-400 mg daily. 1, 5, 2, 7

Oral Loading Regimens by Indication

Ventricular arrhythmias:

• Loading: 800-1600 mg/day in divided doses until 10 g total delivered 1, 2, 7
• Maintenance: 200-400 mg/day 1, 2, 7

Atrial fibrillation:

• Loading: 600-800 mg/day in divided doses until 10 g total delivered 1, 2, 7
• Maintenance: 200 mg/day 1, 2, 7
• Higher initial doses (up to 1200 mg daily) may be used in monitored inpatient settings, though this increases adverse effect risk 7

Pharmacological Cardioversion Expectations

• Most conversions to sinus rhythm occur after 6-8 hours of therapy 2, 8
• Conversion rates: 34-69% with bolus-only IV regimens, 55-95% with bolus plus continuous infusion 2, 8
• Higher doses (>1500 mg/day total) are superior to placebo 8
• Important: The full antiarrhythmic effect may take days to weeks despite adequate serum levels due to amiodarone's extremely long half-life (oral: 26-107 days) 2, 7

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Transition from IV to Oral Therapy

Begin oral amiodarone while the IV infusion continues at 0.5 mg/min, using a duration-based dosing strategy that accounts for tissue drug already accumulated during IV therapy. 5, 4

Duration-Based Conversion Protocol

After <1 week of IV amiodarone:

• Start 800-1600 mg oral daily 5, 7

After 1-3 weeks of IV amiodarone:

• Start 600-800 mg oral daily 5, 7, 4

After >3 weeks of IV amiodarone:

• Start 400 mg oral daily 7

Transition Strategy

• Continue IV infusion at 0.5 mg/min for 24 hours after first oral dose, then discontinue 5
• Continue oral loading until cumulative 10 g total is reached 5, 7
• After completing 10 g load, reduce to maintenance 200-400 mg daily (some patients require only 100-200 mg daily) 5, 7

Mandatory Drug Interaction Management During Transition

Digoxin:

• Reduce dose by 50% immediately when starting amiodarone (amiodarone doubles digoxin levels) 5

Warfarin:

• Reduce dose by 30-50% and check INR within 3-5 days (amiodarone significantly increases INR) 1, 5

Other rate-control agents:

• Reduce or discontinue beta-blockers and calcium channel blockers as amiodarone's rate-control effect develops 5

Monitoring During Transition

• Daily 12-lead ECG to assess QT interval (hold if QT >500 ms) and detect new heart block 5
• Heart rate every 4-6 hours initially, then at least daily 5
• Continuous telemetry for at least 24 hours after IV discontinuation 5
• Blood pressure monitoring for persistent hypotension 5
• Watch for bradycardia (occurs in 1-3% on oral therapy, 4.9% on IV therapy) and AV block 5

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Special Populations and Contraindications

Absolute Contraindications to IV Amiodarone

• Cardiogenic shock 3
• Marked sinus bradycardia 3
• Second- or third-degree AV block without functioning pacemaker 3
• Known hypersensitivity to amiodarone or iodine 3

Wolff-Parkinson-White Syndrome

• Never use beta-blockers, digoxin, adenosine, lidocaine, or calcium channel blockers in WPW with AF (they facilitate accessory pathway conduction and can cause VF) 1
• Amiodarone is Class IIa for rate control in WPW patients with accessory pathways 1

Heart Failure Patients

• Amiodarone is the preferred antiarrhythmic in patients with heart failure or reduced ejection fraction (Class IC agents are contraindicated with structural heart disease) 2, 8
• Use with caution in moderate-to-severe LV dysfunction due to negative inotropic effects 2

Renal Impairment

• No dose adjustment needed (amiodarone undergoes hepatic metabolism, not renal excretion) 2

Pulmonary Disease

• Relatively contraindicated in significant lung disease; if no alternative exists, use lowest effective dose and shortest duration 2

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Long-Term Efficacy and Maintenance

• With appropriate loading, approximately 62% of patients remain in sinus rhythm at 1 year (versus 23% with Class I agents) 5
• Median time to AF recurrence: 487 days with amiodarone versus 74 days with sotalol 5
• Virtually all patients develop side effects at maintenance doses of 600 mg daily; use 200-400 mg daily for maintenance 9
• Most adverse effects are dose- and duration-dependent 2, 9, 10