What is the recommended dosage of N-acetyl cysteine (NAC) for a patient?

N-Acetylcysteine Dosage

For Acetaminophen Overdose

The standard N-acetylcysteine (NAC) dosing regimen for acetaminophen overdose consists of an oral loading dose of 140 mg/kg followed by 70 mg/kg every 4 hours for 17 additional doses (total 72-hour protocol), or an intravenous regimen of 150 mg/kg over 15 minutes, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours. 1, 2

Oral Dosing Protocol

• Loading dose: 140 mg/kg of body weight administered immediately 1, 2
• Maintenance doses: 70 mg/kg every 4 hours for 17 additional doses (total of 18 doses over 72 hours) 1, 2
• The 20% NAC solution must be diluted to 5% concentration using diet cola or other diet soft drinks (3 mL diluent per 1 mL of 20% solution) 2
• If water is used as diluent, administration must be via gastric or Miller-Abbott tube 2

Intravenous Dosing Protocol

• Loading dose: 150 mg/kg infused over 15 minutes 1
• Second dose: 50 mg/kg infused over 4 hours 1
• Third dose: 100 mg/kg infused over 16 hours 1
• Total duration: 20 hours for the standard IV protocol 1

Timing Considerations

• Initiate NAC immediately if ≤24 hours have elapsed since ingestion, regardless of acetaminophen level results 1, 2
• Maximum efficacy occurs when treatment begins within 8-10 hours of ingestion 1
  • Treatment <8 hours: 2.9% severe hepatotoxicity 1
  • Treatment 10-24 hours: 53% severe hepatotoxicity with 5% mortality 1
• NAC still provides benefit when started up to 24 hours post-ingestion, though efficacy decreases with time 1

Massive Overdose Modifications

For acetaminophen concentrations plotting above the "300-line" on the Rumack-Matthew nomogram, consider step-wise increases in NAC dosing 3:

• Standard dosing may be insufficient for massive overdoses 3
• Higher concentrations (450-line, 600-line) may require further dose escalation 3

Special Clinical Scenarios

• Extended-release formulations: Use standard dosing protocol but extend monitoring duration due to prolonged absorption 1
• Repeated supratherapeutic ingestions (>4g per 24 hours): Apply the standard 72-hour oral protocol 1
• Unknown time of ingestion or unreliable history: Administer NAC and assume potentially toxic overdose 1, 2
• Established hepatic failure: Use IV NAC regardless of time since ingestion (mortality reduction from 80% to 52%) 1

High-Risk Patients

Patients at increased risk for acetaminophen toxicity should receive NAC even at lower acetaminophen levels 1:

• Chronic alcohol users 1
• Fasting patients 1
• Those with baseline hepatic dysfunction 1

Management of Vomiting

• If the patient vomits any oral dose within 1 hour of administration, repeat that dose 2
• For persistent vomiting preventing oral retention, administer NAC via duodenal intubation 2
• Dilution of NAC to 5% concentration minimizes gastrointestinal aggravation 2

Activated Charcoal Considerations

• Activated charcoal adsorbs NAC and may reduce effectiveness (up to 96% adsorption in vitro) 2, 4
• If activated charcoal has been given, perform gastric lavage before administering NAC 2
• Do not delay NAC administration while managing activated charcoal 1

Monitoring Requirements

Monitor throughout treatment 2:

• Baseline: acetaminophen level, AST, ALT, bilirubin, PT, creatinine, BUN, glucose, electrolytes 2
• Daily monitoring if acetaminophen level is in potentially toxic range 2

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For COPD Exacerbation Prevention

For patients with moderate to severe COPD and ≥2 exacerbations in the previous 2 years, oral NAC 600 mg twice daily reduces exacerbation rates. 5

Dosing for COPD

• Standard dose: 600 mg orally twice daily (1,200 mg total daily dose) 5
• This regimen reduced exacerbation rate from 1.49 to 1.16 (RR 0.78) in a large multicenter trial of 1,006 patients 5
• Alternative dosing of 600 mg once daily showed 41% reduction in exacerbation rates in smaller studies 5

Patient Selection

• Patients already on maintenance bronchodilator therapy and inhaled corticosteroids who continue having periodic exacerbations 5
• More effective in GOLD II COPD compared to GOLD III disease 5

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For Chemotherapy-Induced Neuropathy Prevention

NAC 1,200 mg orally daily may reduce platinum-based chemotherapy neurotoxicity, though evidence is limited. 5

Dosing for Neuropathy Prevention

• Dose studied: 1,200 mg orally daily during oxaliplatin-based chemotherapy 5
• In a small pilot study (n=14), grade 2-4 sensory neuropathy occurred in 20% with NAC versus 89% with placebo after 12 cycles 5

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Contraindications and Cautions

Not Recommended

• Triple therapy with prednisone, azathioprine, and NAC is NOT recommended for idiopathic pulmonary fibrosis 5
• NAC is not approved for parenteral injection outside of specific acetaminophen overdose protocols 2

Adverse Effects

• Oral NAC commonly causes nausea, vomiting, and gastrointestinal symptoms, especially at high doses for acetaminophen overdose 2, 6
• Rash with or without mild fever occurs rarely 2
• Allergic reactions may require discontinuation, antihistamines, or epinephrine for bronchospasm 7
• Safety profile at doses up to 3,000 mg/day is generally similar to standard doses 6

Storage and Preparation

• Diluted solutions should be freshly prepared and used within 1 hour 2
• Unopened 20% solution vials can be refrigerated up to 96 hours after opening 2