What is the recommended dosage for N-acetylcysteine (NAC) supplementation?

NAC Supplementation Dosing

For acetaminophen overdose, administer oral NAC at 140 mg/kg loading dose followed by 70 mg/kg every 4 hours for 17 additional doses (72-hour protocol), or intravenously at 150 mg/kg over 15 minutes, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours (21-hour protocol). 1, 2, 3

Context-Specific Dosing Protocols

Acetaminophen Overdose (Primary Indication)

Oral Regimen:

• Loading dose: 140 mg/kg by mouth or nasogastric tube, diluted to 5% solution 1, 3
• Maintenance dose: 70 mg/kg every 4 hours for 17 additional doses (total 72 hours) 1, 3
• This oral regimen is as effective as IV and may be superior when treatment is delayed 2

Intravenous Regimen:

• Loading dose: 150 mg/kg in 5% dextrose over 15 minutes 1, 4
• Second dose: 50 mg/kg over 4 hours 1, 4
• Third dose: 100 mg/kg over 16 hours (total 21-hour protocol) 1, 4

Critical Timing Considerations:

• Initiate NAC within 8 hours of ingestion for maximal benefit—only 2.9% develop severe hepatotoxicity when treated this early 2
• Efficacy decreases with delay: 6.1% hepatotoxicity at 10 hours, 26.4% at 10-24 hours 2
• Still administer NAC even beyond 24 hours post-ingestion—it reduces mortality from 80% to 52% in fulminant hepatic failure regardless of timing 2

Massive Acetaminophen Overdose (>300-line on nomogram)

For acetaminophen concentrations plotting above the 300-line, consider step-wise dose increases: 5

• Standard dosing may be insufficient for massive overdoses
• Further increases recommended at 450-line and 600-line thresholds 2, 5
• This represents emerging evidence for dose escalation in extreme cases

Contrast-Induced AKI Prevention

The evidence for NAC in contrast-induced AKI is conflicting and weak, but given its safety profile: 6

• Dose: 1,200 mg by mouth twice daily for 2 days 6
• Administer together with intravenous isotonic crystalloid—never use NAC as a substitute for IV fluids 6
• A large 2011 RCT of 2,308 patients showed no benefit, but oral NAC is inexpensive and largely devoid of adverse effects at this dose 6
• Do not use intravenous NAC for contrast prophylaxis—it is associated with potentially serious adverse effects without proven effectiveness 6

Chronic Respiratory Diseases

For chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, bronchiectasis: 7, 8

• Standard licensed dose: 600 mg/day orally 7
• Higher doses studied: Up to 3,000 mg/day with similar safety profile 7
• Optimal dose for radiation-induced respiratory disease: 1,200 mg/day showed best clinical and antioxidant effects 8
• Gastrointestinal symptoms may occur but are no more common than placebo 7

Special Clinical Scenarios Requiring Extended Treatment

Continue NAC beyond standard protocol in these situations: 2

• Delayed presentation (>24 hours post-ingestion)
• Extended-release acetaminophen formulations
• Repeated supratherapeutic ingestions
• Unknown time of ingestion with detectable acetaminophen levels
• Any elevation in AST or ALT above normal
• Chronic alcohol use (lower threshold for toxicity)

Critical Pitfalls to Avoid

Do not delay NAC while awaiting confirmatory levels if there is strong suspicion of significant acetaminophen overdose 1

Activated charcoal may be given just prior to NAC if patient presents within 4 hours, but do not delay NAC administration even if charcoal has been given 1, 2

The Rumack-Matthew nomogram does NOT apply to presentations >24 hours after ingestion or repeated supratherapeutic ingestions—base treatment decisions on acetaminophen levels, liver function tests, and clinical presentation 2

Intravenous NAC carries risk of allergic reactions—monitor for anaphylactoid reactions and manage with antihistamines and epinephrine if needed 4