Maximum Dose of Acetylcysteine in Adults
For acetaminophen overdose, the standard maximum dose is 300 mg/kg administered over 20-21 hours (loading dose of 140 mg/kg followed by 70 mg/kg every 4 hours for 17 doses), though higher doses up to 400-500 mg/kg may be considered in massive overdoses with acetaminophen concentrations above the "300-line" on the Rumack-Matthew nomogram. 1, 2
Standard Dosing Protocol
The FDA-approved regimen for acetaminophen overdose consists of: 1
- Loading dose: 140 mg/kg
- Maintenance dose: 70 mg/kg every 4 hours for 17 doses
- Total dose: 300 mg/kg over approximately 72 hours (oral protocol) or 20-21 hours (IV protocol)
This translates to a maximum total dose of approximately 21,000 mg (21 grams) for a 70 kg adult using the standard protocol. 1
Intravenous Dosing Variations
Standard IV Protocol
The 21-hour IV protocol delivers 300 mg/kg total: 1
- Loading: 150 mg/kg over 15 minutes
- Maintenance: 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours
Extended 48-Hour Protocol
A 48-hour IV protocol has been studied delivering higher total doses: 3
- Loading: 140 mg/kg
- Maintenance: 70 mg/kg every 4 hours for 12 doses
- Total dose: 980 mg/kg (approximately 68,600 mg for a 70 kg adult)
- This protocol showed low hepatotoxicity rates (18.1% overall, 3.4% when treated within 10 hours) with acceptable adverse event profiles 3
Massive Overdose Considerations
For massive acetaminophen overdoses (>30 g or >500 mg/kg), higher NAC doses may be warranted: 2, 4
- Patients with acetaminophen concentrations above the "300-line" on the nomogram develop hepatotoxicity at higher rates despite standard NAC dosing 2
- Modified regimens providing 400-500 mg/kg total NAC over 21-22 hours have been proposed for concentrations above the 300 mg/L line 4
- Step-wise dose increases at the 300-, 450-, and 600-lines have been suggested, though optimal dosing remains under investigation 2
Important caveat: The evidence for routine high-dose NAC in massive overdoses is limited, and most patients respond adequately to standard dosing. 4 The standard 300 mg/kg regimen remains effective in the majority of large overdoses. 4
Non-Acetaminophen Indications
For acute liver failure of any etiology (not just acetaminophen), NAC improves outcomes: 5
- Standard acetaminophen overdose dosing is typically used
- Most beneficial when initiated early in patients with grades I-II hepatic encephalopathy 5
For chronic conditions like COPD, much lower doses are used: 6
- Standard dose: 1200 mg daily
- Up to 1800 mg daily has been studied safely 6
Safety Considerations
Common adverse effects include: 6, 5
- Nausea, vomiting, and gastrointestinal symptoms
- Skin rash (<5% of patients) 6
- Transient bronchospasm (1-2% of patients) 6
- Anaphylactoid reactions (more common with IV administration)
Patients with asthma or atopic histories should preferentially receive oral rather than IV NAC when clinically appropriate to minimize bronchospasm and anaphylactoid reaction risk. 6
Duration of Treatment
Treatment duration can be shortened in selected low-risk patients: 7
- Patients with normal ALT and creatinine at presentation and 12 hours, plus acetaminophen <20 mg/L at 12 hours, may safely discontinue NAC after 12 hours (250 mg/kg total dose) 7
- This shorter regimen is not appropriate for patients presenting late (>24 hours post-ingestion) or with evidence of organ toxicity 8