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

N-acetylcysteine (NAC) Dosing for Acetaminophen Overdose

The recommended dosage of N-acetylcysteine (NAC) for acetaminophen overdose is a loading dose of 140 mg/kg orally, followed by maintenance doses of 70 mg/kg every 4 hours for 17 doses (72-hour protocol). 1, 2

Administration Routes and Dosing Protocols

Oral Administration (FDA-approved protocol)

• Loading dose: 140 mg/kg body weight
• Maintenance dose: 70 mg/kg every 4 hours for 17 doses
• Dilute the 20% solution with diet cola or other diet soft drinks to a final concentration of 5%
• If administered via gastric tube, water may be used as diluent 2
• If patient vomits within 1 hour of administration, repeat the dose 2

Intravenous Administration

• Loading dose: 150 mg/kg over 15-60 minutes
• Maintenance doses: 50 mg/kg over 4 hours, followed by 100 mg/kg over 16 hours 1

Treatment Decision Algorithm

1. Initiate NAC immediately if:

   • 24 hours or less have elapsed since ingestion
   • Acetaminophen level is at or above the "possible toxicity" line (≥100 mg/L at 4 hours post-ingestion)
   • Time of ingestion is unknown with suspicion of overdose 1, 2

2. Laboratory monitoring:

   • Draw blood for pre-treatment acetaminophen plasma assay
   • Baseline SGOT, SGPT, bilirubin, prothrombin time, creatinine, BUN, blood sugar, and electrolytes 2
   • Use Rumack-Matthew nomogram to determine risk of hepatotoxicity

3. Determine subsequent action based on pre-treatment plasma acetaminophen level:

   • If level is in toxic range: Continue with maintenance doses
   • If level could not be obtained: Continue with maintenance doses
   • If level is clearly in non-toxic range and overdose occurred ≥4 hours before assay: Discontinue NAC
   • If level is in non-toxic range but time of ingestion unknown or <4 hours: Obtain second plasma level 2

Special Considerations

Massive Overdose (>30g or >500 mg/kg)

• Consider increased NAC dosing
• Continue NAC beyond standard protocol if evidence of ongoing liver injury 1
• For acetaminophen concentrations above the "300-line," higher rates of hepatotoxicity occur, suggesting benefit from increased dosing 3

Timing of Treatment

• Early NAC treatment (within 8-10 hours) is most effective in preventing hepatotoxicity
• Late NAC treatment (10-24 hours) is still beneficial but less effective 1
• Hepatotoxicity developed in only 6.1% of patients when NAC was started within 10 hours, compared to 26.4% when started 10-24 hours after ingestion 4

Weight Considerations

• For patients weighing >100 kg, clinical practice often uses actual weight rather than capped weight
• In a study of patients >100 kg, median dosing was 140 mg/kg for oral NAC and 150 mg/kg for IV NAC 5

Duration of Treatment

• Traditional protocols recommend 72 hours for oral administration
• Some evidence suggests shorter courses (24-36 hours) may be effective in patients without evidence of developing hepatotoxicity 6
• Continue treatment until clinical improvement, normalization of acid-base status, and resolution of organ dysfunction 1

Monitoring and Adverse Effects

• Monitor for NAC-related adverse effects (10-15% of patients):

  • Hypersensitivity reactions
  • Nausea and vomiting
  • Urticaria or bronchospasm (rare) 1

• If adverse reactions occur:

  • Temporarily discontinue infusion
  • Administer antihistamines if needed
  • Restart at a slower rate 1

• Continue laboratory monitoring:

  • Serial acetaminophen levels
  • Liver function tests
  • Coagulation parameters
  • Renal function 1

Important Caveats

1. Do not delay NAC administration while awaiting acetaminophen level results if overdose is suspected and <24 hours have elapsed since ingestion.

2. Activated charcoal adsorbs NAC and may reduce its effectiveness. If activated charcoal has been administered, perform lavage before administering NAC 2.

3. Persistent vomiting may require duodenal intubation for NAC administration or switching to intravenous route 2.

4. NAC efficacy decreases with time - there is no difference in outcome when started 0-4 or 4-8 hours after ingestion, but efficacy decreases significantly with further delay 4.