Amiodarone Administration Considerations
Critical Administration Requirements
Amiodarone must be administered through a central venous catheter whenever possible, using a volumetric infusion pump with an in-line filter, and concentrations should not exceed 2 mg/mL for peripheral administration to prevent phlebitis. 1
Intravenous Dosing Protocol
Loading dose: Administer approximately 1000 mg over the first 24 hours using the following regimen: 150 mg over 10 minutes (rapid loading), followed by 1 mg/min for 6 hours (360 mg), then 0.5 mg/min for the remaining 18 hours 1
Maintenance infusion: Continue at 0.5 mg/min (720 mg per 24 hours) after the first 24 hours, which can be maintained for 2-3 weeks regardless of age, renal function, or left ventricular function 1
Do not exceed an initial infusion rate of 30 mg/min, as higher rates have resulted in hepatocellular necrosis, acute renal failure, and death 1, 2
Breakthrough arrhythmias: Administer 150 mg supplemental infusions mixed in 100 mL D5W over 10 minutes to minimize hypotension 1
Equipment and Solution Preparation
Use volumetric infusion pumps only - drop counter sets can underdose by up to 30% due to altered surface properties 1
Concentration limits: For infusions >1 hour, do not exceed 2 mg/mL unless using a central line; concentrations >3 mg/mL cause high rates of peripheral phlebitis 1
Container requirements: Use glass or polyolefin bottles with D5W for infusions exceeding 2 hours; avoid evacuated glass containers which cause precipitation 1
Tubing considerations: While amiodarone adsorbs to PVC tubing and leaches plasticizers (DEHP), all clinical experience uses PVC tubing at the recommended concentrations 1
Absolute Contraindications
Do not administer amiodarone in patients with second- or third-degree AV block or severe sinus node dysfunction without a functioning pacemaker, as drug-related bradycardia occurs in 4.9% of patients. 3, 4, 2
Heart transplant recipients should not receive amiodarone 4
Pre-excitation syndromes with atrial fibrillation are contraindicated for IV amiodarone, as it may accelerate ventricular response and precipitate ventricular fibrillation 4
Critical Drug Interactions Requiring Dose Adjustments
Warfarin Management
Reduce warfarin dose by 50% when initiating amiodarone, as it inhibits CYP2C9 and causes sudden, pronounced increases in INR 5
Monitor PT/INR at least weekly during the first 6 weeks, with peak interaction effects occurring at approximately 7 weeks 5
Digoxin Management
Reduce digoxin dose by 50% when starting amiodarone, as levels predictably double due to inhibition of renal tubular secretion and P-glycoprotein transport 5, 4
Monitor digoxin levels closely after coadministration 5
Other Significant Interactions
Beta-blockers and calcium channel blockers: Amiodarone inhibits CYP2D6 and CYP3A4, creating additive bradycardic effects; use extreme caution and monitor heart rate continuously 5, 3
Statins: Increased risk of myopathy and rhabdomyolysis due to CYP3A4 inhibition 4
Grapefruit juice: Absolutely prohibited during oral amiodarone therapy, as it inhibits CYP3A-mediated metabolism and increases plasma levels 5, 1
Mandatory Baseline Assessment
Before initiating amiodarone, obtain complete history and physical examination with specific attention to heart failure, arrhythmias, concomitant medications, plus baseline chest radiograph, thyroid studies (TSH, free T4), liver transaminases, pulmonary function tests with DLCO, and ophthalmologic examination if visual impairment exists. 5, 4
Continuous Monitoring During IV Administration
Cardiovascular Monitoring
Continuous ECG monitoring is mandatory for heart rate, AV conduction abnormalities, and QT prolongation 3, 4
Monitor for hypotension (occurs in 16% of patients); treat by slowing infusion rate, using vasopressors, positive inotropes, or volume expansion as needed 2
Monitor for bradycardia (occurs in 4.9%); treat by slowing or discontinuing infusion; have temporary pacemaker available for patients with predisposition to bradycardia or AV block 3, 2
QT Interval Monitoring
Document baseline QTc before initiation and monitor at least every 8 hours during infusion 4
Consider dose reduction or discontinuation if QTc exceeds 500 ms 4
Despite frequent QT prolongation, torsades de pointes occurs in <2% of patients, making amiodarone safer than pure potassium channel blockers 4, 2
Regular Follow-Up Monitoring Schedule
After the loading phase, monitor every 6 months with: history and physical directed at adverse effects, heart rate surveillance, thyroid studies, liver transaminases, and chest radiograph if pulmonary symptoms develop. 5
Specific Monitoring Parameters
Thyroid function: Check TSH and free T4 every 6 months, as both hypothyroidism and thyrotoxicosis can occur 5, 4
Liver enzymes: Monitor ALT, AST, and GGT every 6 months; discontinue if levels exceed 3 times normal unless patient has life-threatening arrhythmia 5, 4
Pulmonary assessment: Obtain chest radiograph and PFTs with DLCO at baseline and if any respiratory symptoms develop (cough, dyspnea, fever) 5, 4
Ophthalmologic: Monitor for visual symptoms; corneal microdeposits occur in nearly all patients but are usually asymptomatic 5
High-Risk Clinical Scenarios
Bradycardia Management
Use extreme caution in patients with heart rate <60 bpm; amiodarone is relatively contraindicated unless a pacemaker is in place or the situation is immediately life-threatening 3
If heart rate decreases by 10 bpm during infusion, reduce the infusion rate immediately 3
Consider alternative rate control agents (beta-blockers, calcium channel blockers) first in stable patients 3
Pulmonary Toxicity Warning
Early-onset pulmonary toxicity (days to weeks) has been reported with IV amiodarone, presenting as pulmonary infiltrates, bronchospasm, wheezing, fever, dyspnea, or hypoxia 2
Adult respiratory distress syndrome (ARDS) occurs in 2% of patients during 48-hour therapy; postoperative patients are at particular risk 2
Pulmonary toxicity is the most serious adverse effect and can be fatal; maintain high suspicion for new respiratory symptoms 4, 2
Hepatotoxicity Risk
Acute centrolobular hepatocellular necrosis leading to hepatic coma and death has occurred with excessively rapid loading infusions 1, 2
Approximately 54% of patients have baseline liver enzyme elevations; this is not a contraindication, but requires close monitoring 2
Transition to Oral Therapy
When switching from IV to oral amiodarone, the dose depends on duration of IV therapy and accounts for 50% oral bioavailability; clinical monitoring is particularly important in elderly patients. 1
- After <1 week IV: Start 800-1600 mg oral daily
- After 1-3 weeks IV: Start 600-800 mg oral daily
- After >3 weeks IV: Start 400 mg oral daily 1
Special Population Considerations
Patients with Structural Heart Disease
Amiodarone can be safely used in patients with left ventricular dysfunction, heart failure, or post-myocardial infarction, unlike many other antiarrhythmics 4, 6
Minimal negative inotropic activity makes it preferred in patients with reduced ejection fraction 6, 7
Hemodialysis Patients
No dose adjustment required for chronic kidney disease or dialysis patients 4
Use standard loading and maintenance doses as amiodarone is not renally cleared 4
All other monitoring requirements remain the same 4
Pregnancy
- Amiodarone is category D and should be avoided, especially in the first trimester, due to risk of congenital malformations 4, 7
Common Pitfalls to Avoid
Never use drop counter infusion sets - they underdose by up to 30% 1
Never exceed 2 mg/mL concentration for peripheral administration >1 hour 1
Never use evacuated glass containers for admixing - causes precipitation 1
Never administer with incompatible drugs through the same IV line (aminophylline, cefazolin, heparin, sodium bicarbonate) - use separate lines 1
Never forget to reduce warfarin and digoxin doses by 50% when starting amiodarone 5, 4
Never ignore new respiratory symptoms - pulmonary toxicity can be rapidly progressive and fatal 2
The effects and toxicities of amiodarone persist for weeks after discontinuation due to its long half-life 8