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

N-Acetylcysteine (NAC) Dosing Recommendations

The recommended dose of N-acetylcysteine (NAC) for acetaminophen overdose is a loading dose of 140 mg/kg orally, followed by 70 mg/kg every 4 hours for 17 doses, or intravenously as 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

• 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 72-hour treatment) 1, 2, 3
• For patients weighing less than 20 kg (usually under 6 years), calculate the dose specifically - each mL of 20% acetylcysteine solution contains 200 mg of acetylcysteine 2
• Three (3) mL of diluent should be added to each mL of 20% acetylcysteine solution; do not decrease the proportion of diluent 2

Intravenous Administration Protocol

• 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

Treatment Duration Considerations

• The standard protocol for acetaminophen overdose is 72 hours of oral therapy or 20-24 hours of IV therapy 5, 3
• Treatment should be initiated as soon as possible after acetaminophen overdose, ideally within 8-10 hours of ingestion 1, 3
• NAC may still provide benefit when started up to 24 hours after ingestion, though efficacy decreases with time 1, 3
• Some evidence suggests that shorter courses (24-36 hours) may be effective for patients who do not show evidence of hepatotoxicity within that timeframe 5, 6

Special Considerations

• For massive acetaminophen overdoses with levels above the "300-line" on the Rumack-Matthew nomogram, higher doses of NAC may be necessary 7
• Patients at increased risk for acetaminophen toxicity (alcoholics, fasting patients) may develop toxicity at lower doses and should receive NAC even if acetaminophen levels are below typical treatment thresholds 1
• For traumatic liver injury, the same dosing protocol applies as for acetaminophen overdose 4
• NAC can also be administered via nebulization for respiratory conditions: 1-10 mL of 20% solution or 2-20 mL of 10% solution every 2-6 hours; recommended dose for most patients is 3-5 mL of 20% solution or 6-10 mL of 10% solution three to four times daily 2

Monitoring During Treatment

• Liver function tests (AST, ALT, alkaline phosphatase, total bilirubin) should be monitored during treatment 4
• Coagulation parameters (INR, PT) should be monitored during treatment 4
• Monitor for adverse reactions, particularly allergic reactions, which may require discontinuation of infusion and administration of antihistamines 4, 2
• Common adverse effects include stomatitis, nausea, vomiting, fever, rhinorrhea, drowsiness, chest tightness, and rarely bronchospasm 2

Administration Considerations

• NAC solution does not contain antimicrobial agents; minimize contamination of sterile solution 2
• If only a portion of the solution in a vial is used, store the remainder in a refrigerator and use for inhalation only within 96 hours 2
• Certain materials used in nebulization equipment may react with acetylcysteine, particularly iron, copper, and rubber; use equipment made of glass, plastic, aluminum, anodized aluminum, chromed metal, tantalum, sterling silver, or stainless steel 2