N-Acetylcysteine (NAC) Treatment Regimen for Acetaminophen Overdose
The standard recommended dosing regimen for N-acetylcysteine (NAC) in acetaminophen overdose is a total dose of 300 mg/kg administered intravenously over 21 hours in three sequential infusions: 150 mg/kg loading dose over 15-60 minutes, followed by 50 mg/kg over 4 hours, and then 100 mg/kg over 16 hours. 1
Intravenous (IV) Administration Protocol
Standard 21-Hour Protocol
- Loading dose: 150 mg/kg over 15-60 minutes
- Second dose: 50 mg/kg over 4 hours
- Third dose: 100 mg/kg over 16 hours
This protocol is recommended by the FDA for treatment of acetaminophen overdose to prevent or lessen hepatic injury 1.
Oral Administration Protocol
If IV administration is not available, oral NAC can be administered as follows:
- Loading dose: 140 mg/kg (diluted to 5% solution)
- Maintenance dose: 70 mg/kg every 4 hours for 17 doses 2
The total oral treatment duration is typically 72 hours, though research suggests that shorter courses may be effective in certain situations 3.
Treatment Duration Considerations
Standard Fixed Duration
- Complete the full 21-hour IV protocol or 72-hour oral protocol for acute overdoses
Patient-Tailored Duration
Research suggests that treatment duration can be individualized based on:
- Acetaminophen concentration falling below 10 mg/L
- Normalization of liver enzymes (AST <40 IU/L) 4
A study by Tsai et al. found that a patient-tailored approach resulted in treatment durations of:
- 22 hours (mean) for patients without hepatotoxicity
- 97 hours (mean) for patients who developed hepatotoxicity 4
Special Circumstances
Massive Acetaminophen Overdose
For patients with extremely high acetaminophen levels:
- Consider increasing NAC dosing for concentrations above the "300-line" on the Rumack-Matthew nomogram
- Further dose increases may be warranted at the 450-line and 600-line 5
Delayed Presentation
- NAC should be started immediately without waiting for acetaminophen concentration results if presentation is delayed
- Treatment is most effective when started within 8 hours of ingestion but is still indicated up to 24 hours after ingestion 6
Repeated Supratherapeutic Ingestion
- The Rumack-Matthew nomogram does not apply
- Obtain acetaminophen concentration and liver function tests to guide treatment 1
- Treatment is recommended for serum acetaminophen concentrations ≥10 mg/L or elevated aminotransferases (AST or ALT >50 IU/L) 7
Monitoring During Treatment
- Monitor for hypersensitivity reactions (occurs in 10-15% of patients)
- Common side effects include nausea, vomiting, and rarely urticaria or bronchospasm
- If serious hypersensitivity reactions occur, immediately discontinue infusion and initiate appropriate treatment 1
- NAC infusion may be carefully restarted after treatment of hypersensitivity has been initiated
Treatment Response Assessment
- Treatment response is usually rapid in acetaminophen-induced liver failure
- Clinical response typically occurs within 1 week 2
- If there is no response after approximately 1 week of NAC therapy, consideration for hepatic transplantation should be initiated
Common Pitfalls and Caveats
Delayed treatment: Efficacy decreases with delay. Treatment should ideally be started within 8 hours of ingestion, but is still beneficial up to 24 hours 6.
Fluid overload: Total volume administered should be reduced for patients weighing less than 40 kg and for those requiring fluid restriction 1.
Hypersensitivity reactions: Observe patients during and after infusion. Reactions can be managed with antihistamines and slowing the infusion rate 2.
Extended-release preparations: Limited data exists regarding risk stratification. Treatment decisions must be made on a case-by-case basis 7.
Inadequate duration: Discontinuing treatment prematurely can result in hepatotoxicity. Complete the full treatment course unless using a patient-tailored approach with appropriate monitoring 4, 3.