Why does an amiodarone (antiarrhythmic medication) intravenous (IV) drip form bubbles or foam?

Why Amiodarone IV Drip Forms Bubbles/Foam

Amiodarone IV drip forms bubbles or foam primarily due to the polysorbate 80 component in its formulation, which acts as a surfactant and alters the surface properties of the solution. 1

Mechanism of Bubble Formation

The FDA drug label for intravenous amiodarone specifically addresses this phenomenon:

1. Surface Property Alteration: The surface properties of solutions containing injectable amiodarone are altered, which can affect drop size and potentially lead to underdosage if drop counter infusion sets are used 1

2. Polysorbate 80 Effect: Amiodarone contains polysorbate 80, which:

   • Acts as a surfactant (reduces surface tension)
   • Creates a tendency for bubble/foam formation
   • Can leach plasticizers like DEHP from PVC tubing 1

3. Concentration Effects: Higher concentrations of amiodarone (particularly >2 mg/mL) increase the likelihood of these surface property changes and subsequent bubble formation 1

Clinical Implications

This foaming characteristic has important clinical implications:

• Dosing Accuracy: The reduction in drop size can lead to underdosage by up to 30% if drop counter infusion sets are used 1
• Administration Requirements: Amiodarone must be delivered by a volumetric infusion pump rather than gravity drip sets 1
• Vein Irritation: Concentrations greater than 3 mg/mL have been associated with a high incidence of peripheral vein phlebitis 1

Administration Recommendations

To minimize foaming and ensure proper dosing:

• Use volumetric infusion pumps (never drop counters) 1
• Use in-line filters during administration 1
• Administer through a central venous catheter when possible, especially for concentrations >2 mg/mL 1
• For infusions >2 hours, use glass or polyolefin bottles containing D5W (not evacuated glass containers) 1
• Keep concentration ≤2 mg/mL for peripheral administration to reduce irritation 1

Formulation Considerations

The standard formulation of IV amiodarone contains vasoactive solvents (polysorbate 80 and benzyl alcohol) that contribute to both the foaming properties and hypotensive side effects 2. A newer aqueous formulation (Amio-Aqueous) was developed that doesn't contain these vasoactive excipients, potentially reducing both foaming and hypotension risk 2.

Practical Tips for Clinicians

• Expect some degree of foaming with standard amiodarone formulations
• Do not attempt to eliminate bubbles by vigorous shaking (this worsens the problem)
• Ensure proper setup with volumetric pumps and appropriate tubing
• Be aware that the foaming does not indicate medication degradation or contamination
• Monitor patients closely during administration, particularly for hypotension

By understanding the inherent properties of amiodarone that lead to foam formation, clinicians can ensure proper administration while minimizing complications related to this unique characteristic of the medication.