What is the maximum administration rate for amiodarone intravenously and orally?

Amiodarone Maximum Administration Rates

Intravenous Administration

For life-threatening ventricular arrhythmias, the maximum safe infusion rate is 150 mg over 10 minutes for the initial bolus, followed by 1 mg/min for 6 hours, then 0.5 mg/min for 18 hours, not exceeding 2.2 g in 24 hours. 1, 2, 3

Standard IV Loading Protocol

• Initial bolus: 150 mg IV over 10 minutes minimum (diluted in 100 mL D5W) 2, 3
• Early maintenance: 1 mg/min for 6 hours (total 360 mg) 1, 2, 3
• Late maintenance: 0.5 mg/min for 18 hours (total 540 mg) 1, 2, 3
• Maximum 24-hour dose: 2.2 g total 1, 2, 3

Alternative Rapid Loading (Cardiac Arrest)

• Cardiac arrest bolus: 5 mg/kg (approximately 300 mg) IV/IO rapid push, may repeat once to maximum 15 mg/kg daily 1
• Pediatric cardiac arrest: 5 mg/kg rapid bolus (maximum 300 mg), may repeat up to total daily dose of 15 mg/kg 1

Alternative Loading for Stable Arrhythmias

• Weight-based loading: 5-7 mg/kg over 30-60 minutes, followed by continuous infusion 1, 2, 4
• Pediatric stable arrhythmias: 5 mg/kg (maximum 300 mg) over 20-60 minutes, may follow with infusion of 5 mcg/kg per min, increased to maximum 10 mcg/kg per min 1

Critical Safety Considerations for IV Rate

• Never exceed 10-minute infusion time for the 150 mg bolus – faster administration dramatically increases hypotension risk 2, 3
• Concentrations >2 mg/mL require central venous access – peripheral administration at higher concentrations causes severe phlebitis 3
• Infusions >1 hour must not exceed 2 mg/mL concentration unless given via central line 3
• Hypotension occurs in approximately 16% of patients receiving IV amiodarone, requiring blood pressure monitoring and readiness to reduce infusion rate or add vasopressors 2, 3

Supplemental Boluses

• Breakthrough arrhythmias: Additional 150 mg boluses over 10 minutes may be given while maintenance infusion continues, but total 24-hour dose must not exceed 2.2 g 2, 3

---

Oral Administration

For oral loading, the maximum safe dose is 1600 mg/day in divided doses, though most protocols use 600-800 mg/day to minimize toxicity. 1, 5, 2, 4

Standard Oral Loading Regimens

Ventricular arrhythmias:

• Loading: 800-1600 mg/day in divided doses until 10 g total (typically 1-2 weeks) 1, 5, 2, 4
• Maintenance: 200-400 mg/day 1, 5, 2, 4

Atrial fibrillation:

• Loading: 600-800 mg/day in divided doses until 10 g total 1, 5, 2, 4
• Maintenance: 200 mg/day 1, 5, 2, 4

Higher-Dose Oral Loading (Inpatient Only)

• Up to 1200 mg/day may be used in monitored inpatient settings, but this increases adverse effect risk 5, 2
• Single-dose loading: 30 mg/kg as a single oral dose has been used in some protocols 1

Oral Administration Timing

• Conversion typically occurs after 6-8 hours of therapy, not within 1-2 hours 1, 2
• Full antiarrhythmic effect may require days to weeks despite therapeutic serum levels due to extremely long half-life (26-107 days) 5, 2, 6, 7, 8

---

Transition from IV to Oral Dosing

The oral dose after IV therapy is duration-dependent to account for tissue drug accumulation:

• IV <1 week: Start oral 800-1600 mg/day 5, 2, 4, 3
• IV 1-3 weeks: Start oral 600-800 mg/day 5, 2, 4, 3
• IV >3 weeks: Start oral 400 mg/day 5, 2, 4, 3

Continue IV infusion at 0.5 mg/min for 24 hours after first oral dose, then discontinue 2

---

Critical Pitfalls and Monitoring

Rate-Related Toxicity

• Exceeding the 2.2 g/24-hour IV limit has resulted in hepatocellular necrosis, acute renal failure, and death 3
• Infusing the 150 mg bolus faster than 10 minutes markedly increases hypotension and bradycardia risk 2, 3

Mandatory Monitoring During Loading

• Continuous ECG monitoring for bradycardia, AV block, and QT prolongation 1, 2, 4
• Blood pressure checks every 4-6 hours initially, with readiness to reduce rate or add vasopressors 2, 4
• Daily 12-lead ECG – hold therapy if QT >500 ms or new heart block appears 2, 4
• Continuous telemetry for ≥24 hours after IV discontinuation 2

Drug Interactions Requiring Immediate Dose Adjustment

• Reduce digoxin by 50% immediately when starting amiodarone (amiodarone doubles digoxin levels) 5, 2, 4
• Reduce warfarin by 30-50% and check INR in 3-5 days (amiodarone markedly increases INR) 5, 2, 4
• Reduce or discontinue beta-blockers and calcium-channel blockers as amiodarone's rate-control effect develops 2

Contraindications to Rapid Loading

• Severe sinus node dysfunction, second- or third-degree AV block without pacemaker 1, 4
• Baseline QT prolongation with history of torsades de pointes 4
• Severe liver dysfunction 4

Special Population Considerations

• Heart failure/reduced ejection fraction: Amiodarone is preferred over Class I agents (which are contraindicated in structural heart disease), but use caution due to potential negative inotropic effects 2
• Wolff-Parkinson-White with atrial fibrillation: Amiodarone is Class IIa for rate control; avoid beta-blockers, digoxin, adenosine, and calcium-channel blockers as they can precipitate ventricular fibrillation 2
• Renal impairment: No dose adjustment required (hepatically metabolized) 2
• Significant pulmonary disease: Relatively contraindicated; if no alternative exists, use lowest effective dose for shortest duration 2