What is N‑acetylcysteine 600 mg?

What is N-Acetylcysteine (NAC) 600mg?

N-acetylcysteine (NAC) 600mg is a mucolytic medication that breaks down thick respiratory secretions and serves as an antioxidant, primarily used to prevent exacerbations in patients with moderate-to-severe COPD and as a specific antidote for acetaminophen overdose. 1, 2

Primary Mechanisms of Action

• NAC reduces the viscosity of respiratory secretions by cleaving disulfide bonds in mucoproteins, making thick mucus easier to clear from the airways 1
• NAC is rapidly absorbed from the gastrointestinal tract and quickly appears in active form in lung tissue and respiratory secretions 1
• NAC acts as an antioxidant by maintaining or restoring glutathione levels, which protects cells from oxidative damage 2, 1
• After oral administration of 200-400mg, peak plasma concentrations of 0.35-4 mg/L are achieved within 1-2 hours 3

Clinical Indications

COPD Management (Primary Use at 600mg Dose)

• The American College of Chest Physicians recommends NAC 600mg twice daily for chronic prevention in patients with moderate-to-severe COPD (FEV1 30-79% predicted) who have ≥2 exacerbations per year despite optimal inhaled therapy 1
• High-dose NAC (600mg twice daily) reduces annual exacerbation rates by 22% (1.16 vs 1.49 exacerbations per patient-year, RR 0.78) 4, 1
• NAC reduces hospitalizations from 18.1% to 14.1% (risk ratio 0.76), with a number needed to treat of 25 patients to prevent one hospitalization 1
• NAC appears more effective in moderate COPD (GOLD II) compared to severe disease (GOLD III), with longer time to first exacerbation in the moderate group 1, 5

Acetaminophen Overdose

• NAC administered orally is the specific antidote to prevent or lessen hepatic injury following acetaminophen overdose 2
• The loading dose is 140 mg/kg body weight, followed by maintenance doses of 70 mg/kg every 4 hours 2
• NAC protects the liver by maintaining glutathione levels or acting as an alternate substrate for conjugation with the toxic metabolite 2
• Treatment must be initiated within 24 hours of ingestion, with maximum benefit seen when started within 16 hours 2

Acute Liver Failure

• NAC improves transplant-free survival (64% vs 26%, OR 4.81) and overall survival (76% vs 59%, OR 2.30) in acute liver failure from any cause, not just acetaminophen 5

Dosing Regimens

For COPD Prevention

• 600mg orally twice daily (total 1200mg/day) for chronic ongoing use 1, 4
• Low-dose regimens (<1200mg daily) show significantly less benefit (rate ratio 0.87) and are not recommended 1
• Benefits require at least 6 months of continuous therapy to become significant, with optimal effects seen after 1-3 years 1

For Acetaminophen Overdose

• Loading dose: 140 mg/kg orally 2
• Maintenance dose: 70 mg/kg every 4 hours for 17 additional doses 2

Safety Profile and Adverse Effects

• NAC is generally well-tolerated with rare adverse gastrointestinal effects (nausea, vomiting, diarrhea) even with prolonged use 1, 3
• Generalized urticaria has been observed rarely in patients receiving oral NAC 2
• NAC has low toxicity even when combined with other treatments 1, 5
• Protein binding reaches approximately 50% at 4 hours after dosing, with a terminal half-life of 6.25 hours 3

Important Clinical Caveats

• The American College of Chest Physicians recommends against using NAC during acute exacerbations of COPD—it is for chronic prevention only, not acute treatment 1
• While NAC reduces COPD exacerbations, it has not been shown to significantly impact mortality in respiratory disease 1, 5
• For idiopathic pulmonary fibrosis, the American Thoracic Society/European Respiratory Society suggest clinicians NOT use NAC monotherapy, as no significant benefit was found in FVC change, death rates, or acute exacerbations 6
• NAC may be less effective in patients already receiving inhaled corticosteroids for COPD 1
• Activated charcoal adsorbs NAC and may reduce its effectiveness in acetaminophen overdose; lavage before administering NAC if charcoal has been given 2

Patient Selection Algorithm for COPD Use

1. Confirm moderate-to-severe COPD (FEV1 30-79% predicted or GOLD II-III) 1
2. Document ≥2 exacerbations in the previous 2 years 1
3. Verify patient is on optimal inhaled bronchodilator therapy 1
4. Prescribe NAC 600mg orally twice daily for minimum 1-3 years 1
5. Monitor for gastrointestinal side effects and continue long-term as benefits accumulate over time 1