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

N-Acetylcysteine Dosing for Hepatitis

Critical Distinction: Acetaminophen-Induced vs. Non-Acetaminophen Hepatitis

For acetaminophen-induced acute liver failure (the most common scenario requiring NAC), use the standard FDA-approved dosing regimen regardless of timing, as NAC reduces mortality from 80% to 52% even when started late. 1

Standard NAC Dosing for Acetaminophen Hepatotoxicity

Oral Regimen (FDA-approved):

• Loading dose: 140 mg/kg orally or via nasogastric tube, diluted to 5% solution 1, 2
• Maintenance dose: 70 mg/kg every 4 hours for 17 additional doses (total 72-hour protocol) 1, 2
• Dilute 20% NAC solution with diet cola or soft drinks to minimize nausea; if using gastric tube, water is acceptable 2

Intravenous Regimen (FDA-approved):

• Loading dose: 150 mg/kg in 5% dextrose over 15 minutes 1, 3, 4
• Second dose: 50 mg/kg over 4 hours 1, 3, 4
• Third dose: 100 mg/kg over 16 hours (total 21-hour protocol) 1, 3, 4

When to Initiate NAC in Hepatitis Cases

Start NAC immediately without waiting for confirmatory levels in these scenarios:

• Any acute liver failure where acetaminophen ingestion is suspected or possible, even with inadequate history 1, 3, 4
• Aminotransferases (AST/ALT) >3,500 IU/L, which are highly correlated with acetaminophen poisoning 3
• Detectable acetaminophen levels with unknown time of ingestion 3, 4
• Hepatotoxicity (AST/ALT >1,000 IU/L) with suspected acetaminophen exposure 3

Timing and Efficacy Considerations

The AASLD position paper establishes that NAC should be given as early as possible but may still provide value 48 hours or more after ingestion. 1

• Treatment within 8 hours: 2.9% develop severe hepatotoxicity 1, 3
• Treatment within 10 hours: 6.1% develop severe hepatotoxicity 1, 3
• Treatment 10-24 hours: 26.4-32% develop severe hepatotoxicity 1, 3
• Treatment >24 hours: Still beneficial for established hepatic failure, reducing mortality and cerebral edema 1, 3

Special Scenario: Fulminant Hepatic Failure

For patients with established fulminant hepatic failure from acetaminophen, NAC reduces mortality from 80% to 52%, cerebral edema from 68% to 40%, and need for inotropic support from 80% to 48%, regardless of time since ingestion. 1, 3

• Continue NAC until transaminases are declining and INR normalizes 3
• Do not discontinue NAC based on undetectable acetaminophen levels if hepatotoxicity is present 3

Non-Acetaminophen Acute Liver Failure

For non-acetaminophen drug-induced hepatic failure, use the same IV NAC regimen (150 mg/kg loading, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours), as it improves transplant-free survival from 30% to 41%. 5

• Greatest benefit occurs in early-stage hepatic encephalopathy (grades I-II) 5
• Meta-analysis shows overall survival improvement from 59% to 76% 5
• Liver transplant-free survival improves from 26% to 64% 5

Duration of Treatment Modifications

The standard 72-hour oral or 21-hour IV protocol may require extension in specific circumstances:

• Massive overdose (acetaminophen levels above the "300-line" on nomogram): Consider step-wise dose increases at 300-, 450-, and 600-lines 3, 6
• Extended-release formulations: Monitor for prolonged absorption and extend treatment accordingly 3, 4
• Persistently elevated acetaminophen levels: Continue NAC until levels are undetectable and transaminases normalizing 3, 7, 8
• Delayed presentation (>24 hours): Continue until clinical and laboratory improvement 3

Common Pitfalls to Avoid

• Never delay NAC while awaiting acetaminophen levels if hepatotoxicity is suspected—the AASLD explicitly states to begin NAC promptly even with inadequate knowledge of circumstances 1, 3
• Do not use the Rumack-Matthew nomogram for presentations >24 hours post-ingestion; base decisions on acetaminophen levels and liver function tests 3
• Do not stop NAC prematurely if any of these are present: detectable acetaminophen, rising transaminases, any coagulopathy, or AST/ALT above normal 3
• Activated charcoal (if given within 4 hours) should be administered just prior to NAC, not after, as charcoal adsorbs NAC 1, 3, 2

Adverse Effects Management

• Oral route: Nausea, vomiting (most common); can be mitigated by dilution with diet cola 1, 2
• IV route: Anaphylactoid reactions (discontinue temporarily, treat with antihistamines and epinephrine for bronchospasm, then resume) 1, 9
• If persistent vomiting prevents oral administration, switch to IV route 1

Monitoring During Treatment

Monitor these parameters throughout NAC therapy:

• AST, ALT, alkaline phosphatase, total bilirubin daily 1
• INR/PT, creatinine, BUN daily 1
• Acetaminophen levels until undetectable 3, 7
• Blood glucose, electrolytes 1