Can acetylcysteine (N-acetylcysteine) 20% be diluted in water?

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Last updated: November 17, 2025View editorial policy

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Can Acetylcysteine 20% Be Diluted in Water?

Yes, acetylcysteine 20% solution can be diluted in water—the FDA-approved drug label explicitly states that "the 20% solution may be diluted to a lesser concentration with either Sodium Chloride for Injection, Sodium Chloride for Inhalation, Sterile Water for Injection, or Sterile Water for Inhalation." 1

FDA-Approved Dilution Guidelines

The official FDA labeling provides clear direction on dilution practices:

  • The 20% acetylcysteine solution may be diluted with Sterile Water for Injection or Sterile Water for Inhalation to achieve lower concentrations 1
  • For oral administration as an acetaminophen antidote, the 20% solution should be diluted to a final concentration of 5% using diet cola or other diet soft drinks (though water may be used if administered via gastric or Miller-Abbott tube) 1
  • For nebulization/inhalation use, the 20% solution can be diluted with sterile water to appropriate concentrations 1

Specific Dilution Protocols by Route

Oral Administration (Acetaminophen Overdose)

  • Dilute 20% solution to 5% concentration using diet soft drinks as the preferred diluent, or water if using gastric tube administration 1
  • Freshly prepared dilutions should be utilized within one hour 1
  • Loading dose: 140 mg/kg, followed by maintenance doses of 70 mg/kg every 4 hours for 17 total doses 1

Inhalation/Nebulization Use

  • 1-10 mL of 20% solution (or 2-20 mL of 10% solution) may be given every 2-6 hours when nebulized 1
  • The solution may be diluted with sterile water, sodium chloride injection, or sodium chloride inhalation solution 1

Intravenous Preparation (Off-Label in US)

  • For IV use, 150 mL of 20% solution can be added to 1 L of 5% dextrose in water (D5W) to create a 2.6% solution 2
  • This preparation remains stable for at least 60 hours and is free from bacterial contamination 2
  • A simplified protocol uses 30 g in 1 L D5W with 150 mg/kg loading dose over 1 hour, followed by 14 mg/kg/hour for 20 hours 3

Important Stability and Storage Considerations

Acetylcysteine does not contain antimicrobial agents, requiring careful handling to minimize contamination 1:

  • Opened, undiluted vials can be refrigerated and used within 96 hours 1
  • Freshly prepared oral dilutions should be used within 1 hour 1
  • IV preparations in D5W remain stable for 60 hours at room temperature 2

Common Pitfalls and Caveats

  • Do not use reactive materials (iron, copper, rubber) in nebulization equipment; use glass, plastic, aluminum, or stainless steel instead 1
  • Acetylcysteine is NOT approved for parenteral injection in the United States—only oral and inhalation routes are FDA-approved 1
  • If activated charcoal has been given for acetaminophen overdose, lavage before administering acetylcysteine, as charcoal can adsorb up to 96% of the drug 1, 4
  • Water dilution for oral use is less palatable than diet soft drinks; Fresca has been shown to significantly reduce offensive odor and taste compared to water, chocolate milk, or cranberry juice 5

References

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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