Recommended Daily Dose of N-Acetylcysteine (NAC)
The recommended daily dose of NAC for general use is 1,200 mg orally twice daily (total 2,400 mg/day), which has been validated across multiple clinical contexts including contrast-induced nephropathy prevention and COPD management. 1, 2
Context-Specific Dosing Recommendations
For Acetaminophen Overdose (Emergency Use)
- Loading dose: 140 mg/kg orally, followed by 70 mg/kg every 4 hours for 17 additional doses (72-hour protocol) 1, 2
- This is the FDA-approved regimen and should never be underdosed, as proper NAC administration can reduce mortality significantly 1
- Treatment must be initiated within 8 hours of ingestion for maximal hepatoprotection 2
For Contrast-Induced Nephropathy Prevention
- Dose: 1,200 mg orally twice daily for 2 days, surrounding the contrast procedure 1, 2
- However, high-quality evidence does not support efficacy for this indication—the American College of Cardiology Foundation/American Heart Association provides a Class III (No Benefit) recommendation 3
- If used despite guidelines, NAC should always be given together with intravenous isotonic crystalloid, never as a substitute 2, 3
For Chronic Respiratory Diseases (COPD, Chronic Bronchitis)
- Standard dose: 600 mg orally twice daily (total 1,200 mg/day) 4, 5
- This dose has been shown to reduce COPD exacerbation rates (risk ratio 0.78,95% CI 0.67-0.90; p=0.0011) in a large randomized controlled trial 4
- Higher doses (up to 3,000 mg/day) have been studied with similar safety profiles, though gastrointestinal symptoms may occur 6
- For radiation-induced respiratory tract affection, 1,200 mg/day is optimal both clinically and for antioxidant activity 7
For Hereditary Methemoglobinemia
- The role of NAC in methemoglobinemia treatment remains unclear 8
- In vitro studies suggest NAC can act as a cofactor to enhance reduction and increase intracellular glutathione 8
- It has been suggested for use in patients with methemoglobinemia and G6PD deficiency, though specific dosing is not standardized 8
For Chemotherapy-Induced Peripheral Neuropathy Prevention
- Dose studied: 1,200 mg orally (in context of oxaliplatin-based chemotherapy) 8
- A small pilot study (n=14) showed grade 2-4 sensory neuropathy was lower in the NAC group (20%) compared to placebo (73%) after 12 cycles 8
- However, this evidence is limited by small sample size and requires further validation 8
Safety Profile Across Dose Ranges
- NAC is generally well-tolerated at doses ranging from 600 mg to 3,000 mg/day 6
- The most common adverse effects are gastrointestinal symptoms, which occur at similar rates across standard and high doses 6, 4
- In a large COPD trial, 29% of patients on NAC 1,200 mg/day had adverse events compared to 26% on placebo 4
- Oral NAC is inexpensive and largely devoid of serious adverse effects at the doses used for most indications 2, 3
Critical Dosing Pitfalls to Avoid
- Never use once-daily dosing when twice-daily or every-4-hour dosing is indicated, as NAC's pharmacokinetics require more frequent administration for sustained effect 1
- Do not underdose NAC in acetaminophen overdose—this can significantly impact mortality outcomes 1
- Do not delay NAC administration while awaiting confirmatory acetaminophen levels if there is strong suspicion of significant overdose 2
- Avoid using NAC as a substitute for proven interventions (e.g., isotonic saline hydration for contrast-induced nephropathy prevention) 2, 3