What is the recommended N-acetylcysteine (NAC) dose for acetaminophen overdose?

N-acetylcysteine (NAC) Dosing for Acetaminophen Overdose

The standard intravenous NAC regimen for acetaminophen overdose consists of a total dose of 300 mg/kg, with a loading dose of 150 mg/kg over 15-60 minutes, followed by maintenance doses of 50 mg/kg over 4 hours and 100 mg/kg over 16 hours. 1

Oral NAC Regimen

If intravenous administration is not possible, NAC can be administered orally with:

• Loading dose: 140 mg/kg (diluted to 5% solution)
• Maintenance dose: 70 mg/kg every 4 hours for 17 doses 2, 1

Treatment Initiation and Duration

When to Start NAC

• Begin NAC immediately in any case of suspected acetaminophen overdose without waiting for serum acetaminophen levels 1
• NAC should be given as early as possible, ideally within 8 hours of ingestion, but may still be beneficial 48 hours or more after ingestion 2
• NAC is indicated when:
  • Serum acetaminophen ≥10 mg/mL
  • Elevated aminotransferase levels (AST or ALT >50 IU/L)
  • Any case where acetaminophen overdose is suspected or possible 2, 1

Treatment Duration

While the traditional protocol calls for a fixed duration (72 hours for oral, 20-21 hours for IV), evidence suggests that treatment duration can be guided by clinical and laboratory parameters:

• Continue NAC beyond the initial protocol if:
  • Elevated liver enzymes persist
  • INR >2.0
  • Patient remains clinically unstable 1
• Treatment can be discontinued when:
  • Acetaminophen concentration is <10 mg/L
  • Liver enzymes have normalized 3

Special Considerations

High-Risk Populations

Consider lower treatment thresholds for patients with:

• Chronic alcoholism
• Malnutrition
• Use of CYP2E1 inducers 1

Managing Adverse Reactions

• Monitor for hypersensitivity reactions (10-15% of patients)
• Common side effects include nausea, vomiting, and rare urticaria or bronchospasm
• Allergic reactions can be managed with antihistamines and epinephrine if necessary 2, 1

Treatment Efficacy

NAC significantly reduces:

• Hepatotoxicity (18% vs 58%)
• Mortality (0.7% vs 6%)
• Progression to severe encephalopathy (51% vs 75%)
• Need for vasopressors (48% vs 80%) 1

Practical Considerations

• For oral administration, NAC should be diluted to a 5% solution to improve palatability 2
• In patients with ALF, oral administration may be precluded by active gastrointestinal bleeding or worsening mental status, making IV administration necessary 2
• For patients presenting within 4 hours of ingestion, activated charcoal should be administered just prior to starting NAC 2

NAC is highly effective in preventing hepatotoxicity when administered promptly, with benefits still observed even with delayed administration. The dosing regimen should be followed completely, with continuation beyond the standard duration if clinical and laboratory parameters indicate ongoing liver injury.