Why and how do we dilute 1 gm of azithromycin for intravenous (IV) administration?

IV Azithromycin Dilution: Why and How for 1 Gram Dose

Azithromycin 1 gram IV must be diluted to prevent severe infusion site reactions, and should be reconstituted with 4.8 mL sterile water to create a 100 mg/mL solution, then further diluted to either 1 mg/mL (in 500 mL diluent) or 2 mg/mL (in 250 mL diluent) before infusion. 1

Why Dilution is Necessary

The primary reason for dilution is prevention of infusion site reactions:

• Infusion site reactions increase dramatically in both incidence and severity at concentrations of 4-5 mg/mL, with the most frequent reactions being tenderness and erythema 2
• Concentrations up to 2 mg/mL are well tolerated when administered over 1 hour, but higher concentrations cause significant local tissue irritation 2
• Azithromycin should never be given as a bolus or intramuscular injection due to the risk of severe local reactions 1

Step-by-Step Dilution Protocol for 1 Gram

Step 1: Reconstitution

• Add exactly 4.8 mL of Sterile Water for Injection to the 500 mg vial 1
• Use a standard 5 mL non-automated syringe (not an automated dispenser) to ensure precise measurement, as the vial is under vacuum 1
• Shake until all drug is dissolved, creating a 100 mg/mL solution 1
• This reconstituted solution is stable for 24 hours at temperatures below 30°C (86°F) 1

Step 2: Further Dilution

• Transfer 5 mL of the 100 mg/mL solution into an appropriate diluent 1
• Choose one of two concentration options:
  • 1 mg/mL concentration: Add to 500 mL of diluent, infuse over 3 hours 1
  • 2 mg/mL concentration: Add to 250 mL of diluent, infuse over 1 hour 1

Step 3: Compatible Diluents

Acceptable diluents include 1:

• Normal Saline (0.9% sodium chloride)
• 5% Dextrose in Water
• Lactated Ringer's Solution
• 1/2 Normal Saline (0.45% sodium chloride)
• 5% Dextrose in 1/2 Normal Saline with 20 mEq KCl
• Multiple other dextrose/saline combinations

Infusion Rate Requirements

• Minimum infusion time is 60 minutes for the 2 mg/mL concentration 1
• The 1 mg/mL concentration should be infused over 3 hours 1
• Never administer faster than these rates to avoid infusion site reactions 1, 2

Critical Safety Considerations

• Do not mix with other medications: No other IV substances, additives, or medications should be added to azithromycin or infused simultaneously through the same IV line 1
• Inspect for particulate matter: If any particulate matter is visible in the reconstituted fluid, discard the solution 1
• The final diluted solution is stable for 24 hours at room temperature (≤30°C) or 7 days if refrigerated at 5°C 1

Common Pitfalls to Avoid

• Using automated syringes for reconstitution: The vacuum in the vial requires a standard 5 mL syringe for accurate measurement 1
• Exceeding 2 mg/mL concentration: Higher concentrations cause unacceptable infusion site reactions 2
• Infusing too rapidly: Always respect the minimum 1-hour infusion time for 2 mg/mL or 3-hour time for 1 mg/mL 1
• Attempting IM or bolus administration: These routes are contraindicated and will cause severe local reactions 1

Clinical Context

• The recommended IV dose for community-acquired pneumonia is 500 mg daily for at least 2 days, followed by oral therapy 1
• For pelvic inflammatory disease, 500 mg IV daily for 1-2 days is recommended, followed by oral therapy 1
• The low serum concentrations achieved with azithromycin (approximately 0.4 mg/L after 500 mg oral dose) are compensated by extensive tissue penetration, with tissue concentrations exceeding 3 mg/kg in many sites 3