Adverse reactions associated with acetylcysteine
- 1 February 2009
- journal article
- review article
- Published by Taylor & Francis Ltd in Clinical Toxicology
- Vol. 47 (2), 81-88
- https://doi.org/10.1080/15563650802665587
Abstract
Introduction. Paracetamol (acetaminophen) is one of the most common agents deliberately ingested in self-poisoning episodes and a leading cause of acute liver failure in the western world. Acetylcysteine is widely acknowledged as the antidote of choice for paracetamol poisoning, but its use is not without risk. Adverse reactions, often leading to treatment delay, are frequently associated with both intravenous and oral acetylcysteine and are a common source of concern among treating physicians. Methods. A systematic literature review investigating the incidence, clinical features, and mechanisms of adverse effects associated with acetylcysteine. Results. A variety of adverse reactions to acetylcysteine have been described ranging from nausea to death, most of the latter due to incorrect dosing. The pattern of reactions differs with oral and intravenous dosing, but reported frequency is at least as high with oral as intravenous. The reactions to the intravenous preparation result in similar clinical features to true anaphylaxis, including rash, pruritus, angioedema, bronchospasm, and rarely hypotension, but are caused by nonimmunological mechanisms. The precise nature of this reaction remains unclear. Histamine now seems to be an important mediator of the response, and there is evidence of variability in patient susceptibility, with females, and those with a history of asthma or atopy are particularly susceptible. Quantity of paracetamol ingestion, measured through serum paracetamol concentration, is also important as higher paracetamol concentrations protect patients against anaphylactoid effects. Most anaphylactoid reactions occur at the start of acetylcysteine treatment when concentrations are highest. Acetylcysteine also affects clotting factor activity, and this affects the interpretation of minor disturbances in the International Normalized Ratio in the context of paracetamol overdose. Conclusion. This review discusses the incidence, clinical features, underlying pathophysiological mechanisms, and treatment of adverse reactions to acetylcysteine and identifies particular “at-risk” patient groups. Given the commonality of adverse reactions associated with acetylcysteine, it is important to ensure that any adverse event does not preclude patients from receiving maximal hepatic protection, particularly in the context of significant paracetamol ingestion. Further work on mechanisms should allow specific therapies to be developed.Keywords
This publication has 62 references indexed in Scilit:
- Safety and efficacy of intravenous N‐acetylcysteine for acetaminophen overdose: analysis of the Hunter Area Toxicology Service (HATS) databaseCurrent Medical Research and Opinion, 2007
- Acetaminophen-induced acute liver failure: Results of a United States multicenter, prospective studyJournal of Hepatology, 2005
- Paracetamol overdose and hepatotoxicity at a regional Australian hospital: a 4‐year experienceInternal Medicine Journal, 2005
- Oral or Intravenous N-Acetylcysteine for Acetaminophen Poisoning?Annals of Emergency Medicine, 2005
- Concomitant overdosing of other drugs in patients with paracetamol poisoningBritish Journal of Clinical Pharmacology, 2002
- TOXBASE: Poisons information on the internetEmergency Medicine Journal, 2002
- Presentation of poisoned patients to accident and emergency departments in the North of EnglandHuman & Experimental Toxicology, 1996
- Efficacy of Oral N-Acetylcysteine in the Treatment of Acetaminophen OverdoseThe New England Journal of Medicine, 1988
- Intravenous N-acetylcystine: the treatment of choice for paracetamol poisoning.BMJ, 1979
- TREATMENT OF PARACETAMOL (ACETAMINOPHEN) POISONING WITH N-ACETYLCYSTEINEThe Lancet, 1977