What is the basic NAC regimen for acetaminophen overdose (common two- or three-phase protocol)?

What is the basic NAC regimen for acetaminophen overdose (common two- or three-phase protocol)?

• A. 150 mg/kg IV over 60 min, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours
• B. 150 mg/kg IV over 60 min, then 100 mg/kg over 16 hours, then 50 mg/kg over 4 hours
• C. 75 mg/kg over 60 min, then 75 mg/kg over 4 h, then 50 mg/kg over 16 h
• D. 300 mg/kg bolus followed by 100 mg/kg over 8 hours

Answer: (A)

The basic idea is to rapidly replenish glutathione stores so the toxic metabolite of acetaminophen (NAPQI) can be safely detoxified. The standard intravenous N-acetylcysteine regimen does this in three phases: a loading dose of 150 mg/kg given over 60 minutes, followed by 50 mg/kg given over 4 hours, then 100 mg/kg given over 16 hours. This sequence quickly raises NAC levels to support glutathione synthesis and then sustains them to continue detoxification during the critical early period after overdose. The total dose matches the goal of maximizing protection while balancing safety, and the specific order and durations are based on achieving rapid, then maintained, NAC exposure. Other regimens either change the order and amounts of the phases or use a very different approach (for example, a large single bolus or substantially different phase dosing), which are not the standard, evidence-supported protocol.

The basic idea is to rapidly replenish glutathione stores so the toxic metabolite of acetaminophen (NAPQI) can be safely detoxified. The standard intravenous N-acetylcysteine regimen does this in three phases: a loading dose of 150 mg/kg given over 60 minutes, followed by 50 mg/kg given over 4 hours, then 100 mg/kg given over 16 hours. This sequence quickly raises NAC levels to support glutathione synthesis and then sustains them to continue detoxification during the critical early period after overdose.

The total dose matches the goal of maximizing protection while balancing safety, and the specific order and durations are based on achieving rapid, then maintained, NAC exposure. Other regimens either change the order and amounts of the phases or use a very different approach (for example, a large single bolus or substantially different phase dosing), which are not the standard, evidence-supported protocol.