What is the dose of N-Acetylcysteine (NAC)?

From the Guidelines

The recommended dose of NAC for acetaminophen overdose is 140 mg/kg by mouth or nasogastric tube diluted to 5% solution, followed by 70 mg/kg by mouth every 4 hours for 17 doses, or alternatively, an intravenous loading dose of 150 mg/kg in 5% dextrose over 15 minutes, followed by a maintenance dose of 50 mg/kg over 4 hours and then 100 mg/kg over 16 hours. This dosing regimen is based on the most recent and highest quality study available, which is the 2005 AASLD position paper on the management of acute liver failure 1. The study highlights the importance of administering NAC as early as possible, but notes that it may still be of value 48 hours or more after ingestion.

When administering NAC orally, it is essential to dilute the solution to 5% to minimize gastrointestinal side effects, which may include nausea, vomiting, and rare cases of urticaria or bronchospasm. In patients with acute liver failure, oral administration may be precluded due to active gastrointestinal bleeding or worsening mental status, in which case intravenous administration is recommended. Allergic reactions to NAC can be successfully treated with discontinuation, antihistamines, and epinephrine for bronchospasm.

Key considerations when administering NAC include:

• Starting treatment as early as possible
• Using the correct dosing regimen based on the patient's condition
• Monitoring for potential side effects, such as nausea, vomiting, and allergic reactions
• Adjusting the administration route based on the patient's ability to tolerate oral or intravenous therapy. The study by 1 provides the most up-to-date guidance on NAC dosing for acetaminophen overdose, and its recommendations should be followed to ensure optimal patient outcomes.

From the FDA Drug Label

DOSAGE GUIDE AND PREPARATION Doses in relation to body weight are: Loading Dose of Acetylcysteine ** Body Weight Grams of Acetylcysteine mL of 20% Acetylcysteine mL of Diluent Total mL of 5% Solution (kg) (lb) 100-109 220-240 15 75 225 300 90-99 198-218 14 70 210 280 80-89 176-196 13 65 195 260 70-79 154-174 11 55 165 220 60-69 132-152 10 50 150 200 50-59 110-130 8 40 120 160 40-49 88-108 7 35 105 140 30-39 66-86 6 30 90 120 20-29 44-64 4 20 60 80 Maintenance Dose** (kg) (lb) 100-109 220-240 7.5 37 113 150 90-99 198-218 7 35 105 140 80-89 176-196 6.5 33 97 130 70-79 154-174 5.5 28 82 110 60-69 132-152 5 25 75 100 50-59 110-130 4 20 60 80 40-49 88-108 3. 5 18 52 70 30-39 66-86 3 15 45 60 20-29 44-64 2 10 30 40

• The loading dose of N-Acetylcysteine is based on body weight, with a range of 4-15 grams of Acetylcysteine, depending on the patient's weight.
• The maintenance dose is also based on body weight, with a range of 2-7.5 grams of Acetylcysteine, depending on the patient's weight.
• For patients weighing less than 20 kg, the loading dose is 140 mg/kg and the maintenance dose is 70 mg/kg 2.

From the Research

Dose of NAC

• The currently recommended dosing scheme for treating acetaminophen overdose in the United States consists of a loading dose of oral N-acetylcysteine 140 mg/kg, followed by 70 mg/kg every 4 hours for 17 doses, for a total of 72 hours of oral N-acetylcysteine therapy 3.
• A 48-hour IV NAC protocol is safe and effective antidotal therapy for acetaminophen overdose, consisting of a loading dose of 140 mg/kg followed by 12 doses of 70 mg/kg every four hours 4.
• For patients weighing >100 kg, NAC dosing is weight-based, with a loading dose of 150 mg/kg intravenous or 140-mg/kg oral, and clinicians often use an actual weight-based NAC dose rather than a maximum weight cutoff dose 5.
• In cases of massive overdose, additional NAC may be necessary, with recent evidence suggesting that patients with acetaminophen concentrations above the "300-line" develop hepatotoxicity at a higher rate than those below the 300-line, and further increases in doses may be beneficial at the 450-line and 600-lines 6.
• Premature cessation of intravenous NAC therapy can lead to hepatotoxicity, coagulopathy, and renal injury, and acetaminophen concentrations and aminotransferase levels should be evaluated at the completion of the intravenous NAC infusion to ensure complete elimination of acetaminophen and absence of hepatotoxicity 7.