N-acetylcysteine (NAC) Side Effects
N-acetylcysteine (NAC) is generally well-tolerated with a low risk of adverse effects, though gastrointestinal symptoms are the most common side effects experienced by patients. 1
Common Side Effects
- Gastrointestinal effects: Nausea, vomiting, and other gastrointestinal symptoms are the most frequently reported adverse effects, particularly with oral administration and at higher doses 1
- Stomatitis: Inflammation of the mouth and oral mucosa 1
- Unpleasant odor: NAC has a characteristic sulfur smell that some patients find unpleasant 2
- Rhinorrhea: Runny nose can occur, especially with nebulized formulations 1
Serious Side Effects (Less Common)
Anaphylactoid reactions: When administered intravenously (particularly for acetaminophen overdose), NAC can cause anaphylactoid reactions including:
- Rash and pruritus (itching)
- Angioedema
- Bronchospasm
- Rarely, hypotension 2
Bronchospasm: Clinically significant bronchospasm occurs infrequently and unpredictably, even in patients with asthmatic bronchitis 1
Chest tightness: Can occur particularly with nebulized formulations 1
Risk Factors for Adverse Reactions
- Female gender: Women appear more susceptible to anaphylactoid reactions 2
- History of asthma or atopy: Patients with these conditions are at higher risk for adverse reactions 2
- Dose-dependent risk: Higher doses are associated with increased risk of side effects 3
- Route of administration: IV administration tends to cause more immediate reactions than oral administration 2
Special Considerations
Acetaminophen Overdose Treatment
- When used as an antidote for acetaminophen poisoning, NAC's side effects should not prevent completion of therapy, as the benefits far outweigh the risks 4
- Paradoxically, higher serum paracetamol concentrations appear to protect against anaphylactoid reactions to NAC 2
COPD Treatment
- When used for COPD exacerbation prevention (typically 600 mg twice daily), NAC is well tolerated with minimal adverse effects 4
- In the largest study of NAC for COPD (1,006 patients), the incidence of adverse effects did not differ significantly between NAC and placebo groups 4
Parenteral Nutrition in Children
- When added to parenteral nutrition at doses of 20-50 mg/kg/day, NAC has been shown to decrease liver enzyme elevations with minimal side effects 4
Monitoring and Management
- Dilution: Diluting oral NAC can minimize its propensity to cause vomiting 1
- Monitoring: Patients receiving IV NAC should be monitored for anaphylactoid reactions, particularly at the start of treatment when concentrations are highest 2
- Acquired sensitization: Rarely reported, particularly in healthcare workers with frequent and extended exposure 1
Conclusion
While NAC has a generally favorable safety profile, clinicians should be aware of potential adverse effects, particularly gastrointestinal symptoms with oral administration and anaphylactoid reactions with IV administration. The risk of side effects appears to increase with higher doses, but most adverse events are mild and transient 1, 2, 3.