What is the recommended dose of N-acetyl cysteine (NAC) for the treatment of hepatitis?

N-acetylcysteine (NAC) Dosing for Hepatitis

For treatment of acetaminophen-induced hepatitis, N-acetylcysteine should be administered orally with a loading dose of 140 mg/kg followed by maintenance doses of 70 mg/kg every 4 hours for 17 doses, or intravenously with a loading dose of 150 mg/kg over 15-60 minutes, followed by 50 mg/kg over 4 hours and 100 mg/kg over 16 hours. 1

Oral Administration Protocol

1. Loading dose: 140 mg/kg body weight

   • Dilute to a 5% solution using diet cola or other diet soft drinks 2
   • If administered via gastric tube, water may be used as diluent

2. Maintenance dose: 70 mg/kg body weight every 4 hours

   • Continue for a total of 17 doses (72 hours total treatment)
   • If patient vomits within 1 hour of administration, repeat that dose 2

Intravenous Administration Protocol

1. Loading dose: 150 mg/kg over 15-60 minutes
2. First maintenance dose: 50 mg/kg over 4 hours
3. Second maintenance dose: 100 mg/kg over 16 hours 1

Treatment Duration Considerations

The standard treatment duration is 72 hours (17 doses) for oral administration or 20-21 hours for IV administration. However, treatment duration may need to be extended in certain circumstances:

• Patients with very high initial acetaminophen levels (above the "300-line" on the Rumack-Matthew nomogram) 3
• Persistent elevation of acetaminophen levels during treatment
• Extended-release formulation overdoses
• Patients who already have evidence of hepatotoxicity

Monitoring During Treatment

• Daily monitoring of serum bilirubin, INR, serum creatinine, and serum sodium 1
• Monitor liver function tests (AST/ALT) to assess treatment response
• Monitor for adverse effects of NAC:
  • Nausea and vomiting (common)
  • Hypersensitivity reactions (10-15% of patients)
  • Skin rash (<5%)
  • Transient bronchospasm (1-2%) 1

Special Considerations

• Treatment should be initiated as soon as possible after acetaminophen overdose, ideally within 8 hours of ingestion for maximum efficacy 4
• For patients with unknown time of ingestion or presenting >24 hours post-ingestion, NAC should still be administered if acetaminophen toxicity is suspected 5
• For patients with evidence of hepatotoxicity (elevated transaminases) but without hepatic failure, NAC should be considered even in the absence of controlled studies demonstrating efficacy in this specific scenario 5

Treatment Efficacy

NAC is most effective when administered early (within 8-10 hours of acetaminophen ingestion). When administered within this timeframe, NAC can prevent or significantly reduce hepatotoxicity in most patients 4. However, even when administered later, NAC may still provide benefit by reducing disease progression in patients with established hepatic injury 5.

Potential Pitfalls

1. Delayed administration: Efficacy decreases significantly when NAC is administered more than 8-10 hours after acetaminophen ingestion
2. Premature discontinuation: Some patients may require extended treatment beyond the standard regimen
3. Inadequate dosing: Patients with very high acetaminophen levels may require higher NAC doses
4. Management of adverse reactions: Temporary discontinuation of infusion may be necessary for hypersensitivity reactions, followed by restarting at a slower rate

Remember that NAC works by maintaining or restoring glutathione levels or by acting as an alternate substrate for conjugation with the reactive metabolite of acetaminophen 6. This mechanism is critical for preventing or reducing hepatic injury following acetaminophen overdose.