Why is amiodarone mixed with dextrose (intravenous solution)?

Why Amiodarone is Mixed in Dextrose

Amiodarone is mixed in dextrose (D5W) because it forms precipitates when mixed with normal saline or other solutions, which could lead to underdosing, vascular complications, or treatment failure. 1

Compatibility and Stability Considerations

Amiodarone's formulation requirements are specifically outlined in FDA labeling:

• Amiodarone must be diluted in D5W (5% dextrose in water) for intravenous administration
• The drug forms precipitates when mixed with other solutions (including normal saline)
• For infusions longer than 1 hour, concentrations should not exceed 2 mg/mL unless a central venous catheter is used 1
• Amiodarone infusions exceeding 2 hours must be administered in glass or polyolefin bottles containing D5W 1

Administration Requirements

When administering intravenous amiodarone:

• Use a volumetric infusion pump (drop counter infusion sets may lead to underdosing by up to 30%) 1
• Administer through a central venous catheter whenever possible
• Use an in-line filter during administration
• Do not exceed an initial infusion rate of 30 mg/min 1

Important Precautions

Concentration and Rate Limitations

• Concentrations greater than 3 mg/mL in D5W are associated with high incidence of peripheral vein phlebitis 1
• Concentrations of 2.5 mg/mL or less appear less irritating
• Rapid infusions at high concentrations have resulted in serious adverse events including:
  • Hepatocellular necrosis
  • Acute renal failure
  • Death 1

Material Compatibility Issues

• Amiodarone adsorbs to polyvinyl chloride (PVC) tubing
• The drug leaches plasticizers (including DEHP) from intravenous tubing
• Polysorbate 80, a component of amiodarone hydrochloride injection, also leaches DEHP from PVC 1
• Do not use evacuated glass containers for admixing due to potential incompatibility with container buffers 1

Hemodynamic Considerations

The dextrose solution also helps manage amiodarone's hemodynamic effects:

• Intravenous amiodarone can cause hypotension in 16% of patients 2
• Patients with left ventricular ejection fraction less than 0.35 may experience a 20% decrease in cardiac index and elevation of right heart pressures after acute bolus administration 3
• The dextrose solution provides a more stable delivery medium for the drug, helping to minimize these effects

Drug Interactions and Incompatibilities

Amiodarone in D5W forms precipitates with several drugs, requiring separate intravenous administration lines when coadministration is necessary 1. This incompatibility further necessitates the specific dextrose formulation.

Clinical Implications

Understanding amiodarone's formulation requirements is essential for safe administration:

• Always inspect solution for particulate matter and discoloration before administration
• Solution should be clear
• Do not use plastic containers in series connections (risk of air embolism) 1
• When changing from IV to oral amiodarone, clinical monitoring is recommended, particularly for elderly patients 1

By adhering to these specific formulation and administration requirements, clinicians can maximize the efficacy of amiodarone while minimizing the risk of adverse events.