What is the recommended dose of N-acetyl cysteine (NAC) in drug-induced hepatic failure?

N-Acetylcysteine Dosing in Drug-Induced Hepatic Failure

For drug-induced hepatic failure, N-acetylcysteine should be administered intravenously at a loading dose of 150 mg/kg over 15 minutes, followed by 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours. 1, 2

Intravenous Administration Protocol

• The recommended IV NAC regimen for drug-induced hepatic failure consists of a 150 mg/kg loading dose administered over 15 minutes, followed by 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours 1, 2
• Treatment should be initiated as soon as possible after suspected drug-induced liver injury, regardless of the causative agent 3
• NAC therapy should be started without waiting for confirmatory laboratory results when drug-induced hepatic failure is suspected 3

Oral Administration Alternative

• If intravenous administration is not possible, oral NAC can be administered at a loading dose of 140 mg/kg followed by 70 mg/kg every 4 hours for 17 doses 4
• For oral administration, the 20% solution should be diluted with diet cola or other soft drinks to a final concentration of 5% to improve palatability 4
• If the patient vomits within 1 hour of administration, the dose should be repeated 4

Efficacy in Non-Acetaminophen Drug-Induced Liver Injury

• NAC has shown benefit in non-acetaminophen-related acute liver failure, with improved transplant-free survival (41% versus 30%, OR = 1.61,95% CI 1.11–2.34, P = 0.01) 3
• A meta-analysis of adult patients demonstrated improvements in overall survival (76% versus 59%, OR = 2.30,95% CI 1.54–3.45 P <0.0001) and liver transplant-free survival (64% versus 26%, OR = 4.81,95% CI 3.22–7.18, P < 0.0001) 3
• NAC should be initiated early in the course of drug-induced hepatic failure, as its beneficial effects appear to be greater in patients with early-stage hepatic encephalopathy (grades I-II) 3

Monitoring During Treatment

• Monitor liver function tests including AST, ALT, alkaline phosphatase, and total bilirubin during NAC therapy 2
• Track coagulation parameters including INR and PT during treatment to assess effectiveness 2
• Monitor for adverse effects, which may include nausea, vomiting, diarrhea, skin rash (< 5%), or transient bronchospasm (1-2%) 3

Special Considerations

• Patients with chronic liver disease may have altered NAC pharmacokinetics, with increased area under the curve and reduced clearance, potentially requiring dose adjustment 5
• In patients with very high aminotransferases, NAC should be administered even without confirmatory history of drug exposure 1
• The duration of treatment may be adjusted based on clinical response and laboratory parameters, with some evidence suggesting that shorter courses (31 hours median duration) may be effective in certain cases 6

Common Pitfalls and Caveats

• Delaying NAC administration while awaiting laboratory confirmation can reduce its efficacy; treatment should be initiated promptly when drug-induced hepatic failure is suspected 3
• Activated charcoal may adsorb NAC if administered orally; if activated charcoal has been given, consider intravenous NAC administration 4
• NAC may cause anaphylactoid reactions, particularly with the intravenous route; monitor closely during administration, especially in patients with chronic liver disease who may have higher plasma NAC concentrations 5