What volume of fluid is recommended for admixture with atezolizumab (Tecentriq) and bevacizumab (Avastin)?

Recommended Fluid Volume for Atezolizumab and Bevacizumab Admixture

Atezolizumab should be diluted in 0.9% Sodium Chloride Injection to a final concentration between 3.2 mg/mL and 16.8 mg/mL, while bevacizumab is typically administered in its standard volume without additional dilution requirements. 1

Atezolizumab Preparation Guidelines

Dilution Requirements

• Atezolizumab must be diluted in a polyvinyl chloride (PVC), polyethylene (PE), or polyolefin (PO) infusion bag containing only 0.9% Sodium Chloride Injection, USP 1
• The final concentration must be between 3.2 mg/mL and 16.8 mg/mL 1
• For the standard 1200 mg dose, this typically requires:
  • Minimum dilution volume: ~71 mL (to achieve 16.8 mg/mL concentration)
  • Maximum dilution volume: ~375 mL (to achieve 3.2 mg/mL concentration)
  • Common practice: 250 mL total volume

Administration Process

1. Visually inspect the drug product for particulate matter and discoloration
2. Select appropriate vial(s) based on prescribed dose (typically 1200 mg every 3 weeks for HCC) 2
3. Withdraw required volume using sterile needle and syringe
4. Dilute to appropriate concentration in the infusion bag
5. Mix diluted solution by gentle inversion (do not shake) 1

Bevacizumab Preparation Guidelines

Standard Dosing

• Bevacizumab is typically administered at 15 mg/kg IV every 3 weeks when used in combination with atezolizumab for HCC 2
• Unlike atezolizumab, bevacizumab does not require specific dilution to a target concentration range
• It is typically administered in its standard volume as provided by the manufacturer

Administration Considerations

Infusion Duration

• For atezolizumab: Administer initial infusion over 60 minutes; if tolerated, subsequent infusions may be delivered over 30 minutes 1
• For bevacizumab: First dose typically administered over 90 minutes; subsequent doses in 30-60 minutes if well-tolerated 2

Storage of Prepared Solutions

• If not used immediately, atezolizumab solution can be stored:
  • At room temperature for up to 6 hours from preparation time (including infusion time)
  • Under refrigeration (2°C to 8°C) for up to 24 hours 1
• Do not freeze or shake the prepared solution 1

Important Precautions

Infusion Reactions

• Infusion reactions with atezolizumab occur in 1-2% of patients 2
• Bevacizumab-associated infusion reactions occur in <3% during first infusion, with severe reactions in <1% 2
• For grade 1-2 reactions: slow or stop infusion and provide symptomatic treatment
• For grade 3-4 reactions: permanently discontinue the drug 2, 1

Pre-Treatment Requirements

• Before initiating atezolizumab plus bevacizumab for HCC, patients must undergo endoscopic evaluation and treatment for esophageal varices within approximately 6 months due to risk of bleeding with bevacizumab 2, 3

Common Pitfalls to Avoid

• Using solutions other than 0.9% Sodium Chloride for dilution of atezolizumab
• Diluting atezolizumab outside the recommended concentration range
• Administering as an IV push or bolus (both drugs require infusion)
• Co-administering other drugs through the same intravenous line
• Failing to perform endoscopic evaluation before treatment initiation in HCC patients
• Shaking the vials or prepared solutions (can lead to protein denaturation)

By following these specific guidelines for admixture preparation, you can ensure proper administration of atezolizumab and bevacizumab while minimizing the risk of infusion-related reactions and maintaining drug efficacy.