What is the frequency of allergic reactions to N-Acetylcysteine (NAC)?

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Last updated: June 17, 2025View editorial policy

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From the Guidelines

Allergic reactions to N-Acetylcysteine (NAC) are relatively rare, with occasional nausea, vomiting, and rare urticaria or bronchospasm being reported. The frequency of allergic reactions to NAC is not explicitly quantified in the provided study 1, but it is mentioned that NAC has few side effects, including rare urticaria or bronchospasm.

  • Key points to consider when evaluating the risk of allergic reactions to NAC include:
    • The route of administration, with intravenous administration potentially carrying a higher risk of reactions compared to oral formulations
    • The patient's medical history, including conditions such as asthma or atopic conditions that may increase the risk of reactions
    • The importance of prompt treatment with NAC in cases of acetaminophen overdose, as the benefits of treatment generally outweigh the risks of allergic reactions
  • According to the study 1, allergic reactions to NAC may be successfully treated with discontinuation, antihistamines, and epinephrine for bronchospasm, allowing healthcare providers to manage reactions effectively while still providing necessary treatment.
  • It is essential to weigh the potential risks of allergic reactions against the benefits of NAC treatment, particularly in life-threatening conditions such as acetaminophen overdose, where prompt administration of NAC is crucial 1.

From the FDA Drug Label

WARNINGS Generalized urticaria has been observed rarely in patients receiving oral acetylcysteine for acetaminophen overdose. ADVERSE REACTIONS Adverse effects have included ... Acquired sensitization to acetylcysteine has been reported rarely.

Allergic reactions to N-Acetylcysteine (NAC) are rare. The specific frequency is not provided in the drug label, but they are described as occurring rarely 2 and infrequently 2. Key allergic symptoms include:

  • Generalized urticaria
  • Acquired sensitization
  • Dermal eruptions It is essential to monitor patients for these symptoms and discontinue treatment if they occur, unless deemed essential and the symptoms can be controlled 2.

From the Research

Frequency of Allergic Reactions to N-Acetylcysteine (NAC)

  • The frequency of allergic reactions to NAC varies across different studies, with reported incidence rates ranging from 2-48% of treated patients 3.
  • A study published in 2018 found that anaphylactoid reactions to intravenous NAC occurred in 8.2% of treatment courses, with 75.4% of these reactions being cutaneous 4.
  • Another study published in 1994 reported an incidence of adverse reactions to intravenous NAC of 14% in Chinese patients with paracetamol poisoning 5.
  • A case report from 2021 described a severe, unusually delayed anaphylactoid reaction to intravenous NAC in an adolescent, highlighting the importance of close observation beyond the first 1-5 hours of NAC administration 6.

Risk Factors and Management

  • Being female and having taken a single, acute overdose were associated with more severe anaphylactoid reactions to NAC 4.
  • Higher serum acetaminophen concentrations were associated with fewer reactions 4.
  • Management of anaphylactoid reactions to NAC typically involves stopping the infusion, administering antihistamines, and providing supportive care 3.
  • Education about the pathophysiology of these reactions may improve management, as the use of steroids is often inappropriate 3.

Animal Studies

  • A case report from 2022 described anaphylaxis due to first-time intravenous infusion of NAC in a dog, highlighting the potential for allergic reactions in animals as well 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Incidence and management of N-acetylcysteine-related anaphylactoid reactions during the management of acute paracetamol overdose.

European journal of emergency medicine : official journal of the European Society for Emergency Medicine, 2014

Research

Anaphylactoid Reactions to Intravenous N-Acetylcysteine during Treatment for Acetaminophen Poisoning.

Journal of medical toxicology : official journal of the American College of Medical Toxicology, 2018

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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