N-acetylcysteine (NAC) Dosing for Paracetamol (Acetaminophen) Poisoning
For paracetamol poisoning, N-acetylcysteine (NAC) should be administered intravenously with a loading dose of 150 mg/kg over 15-60 minutes, followed by 50 mg/kg over 4 hours, and then 100 mg/kg over 16 hours. 1
Indications for NAC Treatment
NAC is indicated in the following scenarios:
- Acetaminophen level at or above the "possible toxicity" line (≥100 mg/L at 4 hours post-ingestion) on the Rumack-Matthew nomogram 1, 2
- Unknown time of ingestion with suspicion of overdose
- Presentation >8 hours after ingestion with known overdose
- Massive overdose (>30g or >500 mg/kg) 1
IV NAC Dosing Regimen (Preferred)
The current recommended two-bag IV regimen is:
- Loading dose: 150 mg/kg over 15-60 minutes
- Maintenance dose 1: 50 mg/kg over 4 hours
- Maintenance dose 2: 100 mg/kg over 16 hours
- Total dose: 300 mg/kg over approximately 21 hours 1
This two-bag regimen has similar efficacy but significantly fewer adverse reactions compared to the older three-bag regimen 3.
Oral NAC Dosing Regimen (Alternative)
If IV administration is not possible:
- Loading dose: 140 mg/kg (diluted to 5% solution)
- Maintenance dose: 70 mg/kg every 4 hours for 17 doses 1
Special Dosing Considerations
Massive Overdose
For patients with massive overdose (>30g or >500 mg/kg) or with acetaminophen concentrations more than double the nomogram line:
- Consider increased NAC dosing beyond the standard protocol 1
- Continue NAC beyond the standard 21-hour protocol if there is evidence of ongoing liver injury 1
Extended-Release Formulations
- All potentially toxic modified-release paracetamol ingestions (≥10g or ≥200 mg/kg, whichever is less) should receive a full course of acetylcysteine 4
- For extended-release formulations, obtain a second acetaminophen concentration 8-10 hours after ingestion if the 4-hour level is below the toxicity line 2
Monitoring During Treatment
- Monitor for hypersensitivity reactions (occurs in 10-15% of patients) 1
- Common side effects include nausea and vomiting; rare effects include urticaria or bronchospasm 1
- For adverse reactions: temporarily discontinue infusion, administer antihistamines, and restart at a slower rate 1
- Daily monitoring of liver function tests (serum bilirubin, INR), renal function, and electrolytes 1
Duration of Treatment
- Standard duration is 21 hours for IV protocol 1, 3
- Continue NAC beyond standard protocol if:
- Acetaminophen is still detectable in serum
- Evidence of ongoing liver injury (rising transaminases, coagulopathy)
- Severe acidosis persists 1
Common Pitfalls to Avoid
Delayed treatment: NAC is most effective when started within 8-10 hours of ingestion; efficacy diminishes progressively after 8 hours 1, 2
Underestimating risk: The nomogram may underestimate hepatotoxicity risk in patients with chronic alcoholism, malnutrition, or those taking CYP2E1 enzyme-inducing drugs (e.g., isoniazid) 2
Premature discontinuation: Do not stop NAC therapy early in patients with evidence of hepatotoxicity or detectable acetaminophen levels 1
Inadequate monitoring: Failure to monitor for adverse reactions to NAC, which can be managed with temporary discontinuation and antihistamines 1
The SNAP regimen (100 mg/kg over 2 hours followed by 200 mg/kg over 10 hours) has shown similar efficacy with fewer adverse reactions compared to the standard 21-hour regimen in recent research 3, but current guidelines still recommend the standard dosing protocol described above.