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

N-Acetylcysteine (NAC) Dosing Recommendations

For acetaminophen overdose, N-acetylcysteine should be administered orally at a loading dose of 140 mg/kg followed by 70 mg/kg every 4 hours for 17 doses (72-hour protocol), or intravenously at 150 mg/kg over 15 minutes, followed by 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours. 1, 2

Oral Administration Protocol for Acetaminophen Overdose

• Loading dose: 140 mg/kg by mouth or nasogastric tube diluted to 5% solution 1, 2
• Maintenance dose: 70 mg/kg by mouth every 4 hours for 17 doses (total treatment duration of 72 hours) 1, 2, 3
• NAC should be initiated as soon as possible after acetaminophen overdose, ideally within 8-10 hours of ingestion for maximum efficacy 1, 3
• Treatment may still provide benefit when started up to 24 hours after ingestion, though efficacy decreases with time 1, 3

Intravenous Administration Protocol for Acetaminophen Overdose

• Loading dose: 150 mg/kg in 5% dextrose over 15 minutes 4, 1
• First maintenance dose: 50 mg/kg over 4 hours 4, 1
• Second maintenance dose: 100 mg/kg over 16 hours 4, 1
• Total treatment duration: 20-21 hours 1

Dosing Considerations Based on Patient Weight

• For patients weighing less than 20 kg (usually patients younger than 6 years), calculate the dose of acetylcysteine based on the exact weight 2
• Each mL of 20% acetylcysteine solution contains 200 mg of acetylcysteine 2
• For oral administration, three (3) mL of diluent should be added to each mL of 20% acetylcysteine solution to create a 5% solution 2

Special Clinical Scenarios

• For patients with repeated supratherapeutic ingestions (>4g per 24 hours), the standard 72-hour oral protocol or 21-hour IV protocol is still recommended 1
• For extended-release acetaminophen preparations, the standard dosing regimen applies, though monitoring may need to be extended 5, 1
• For patients with very high acetaminophen concentrations (above the "300-line" on the Rumack-Matthew nomogram), higher NAC doses may be considered 6
• For patients with acute liver failure where acetaminophen ingestion is suspected or possible, even without confirmatory history, NAC should be administered using the standard dosing protocol 5, 1

Monitoring During Treatment

• Liver function tests, including AST, ALT, alkaline phosphatase, and total bilirubin, should be monitored during NAC treatment 4
• Coagulation parameters, including INR and PT, should be monitored during NAC treatment 4
• Adverse reactions, particularly allergic reactions, should be monitored and managed promptly 4, 2

Efficacy and Safety Considerations

• When given within eight hours of acetaminophen ingestion, NAC is protective regardless of the initial plasma acetaminophen concentration 3
• There is no difference in outcome whether NAC is started zero to four or four to eight hours after ingestion, but efficacy decreases with further delay 3
• Some evidence suggests that shorter treatment courses (24-36 hours) may be effective for patients who present early and do not develop hepatotoxicity, but this approach should be used with caution and is not standard practice 7, 8
• The 72-hour oral NAC regimen has been shown to be as effective as the 20-hour intravenous regimen, and may be superior when treatment is delayed 3

Common Pitfalls and Caveats

• Do not delay NAC administration while awaiting confirmatory acetaminophen levels if there is strong suspicion of significant overdose 5, 1
• Activated charcoal may be given just prior to starting NAC for patients with known or suspected acetaminophen overdose within 4 hours of presentation 5
• NAC administration should not be delayed even if activated charcoal has been given 5
• Patients at increased risk for acetaminophen toxicity, such as alcoholics or fasting patients, may develop toxicity at lower doses and should receive NAC even if acetaminophen levels are below the typical treatment threshold 1