What are the indications for N-acetylcysteine (NAC)?

From the Guidelines

Acetylcysteine is primarily indicated for the treatment of acetaminophen overdose, particularly in patients with possible or probable risk for hepatotoxicity as determined by the Rumack-Matthew nomogram, to reduce the incidence of severe hepatotoxicity and mortality. The administration of N-acetylcysteine (NAC) in acetaminophen overdose is based on its ability to limit hepatotoxicity by serving as a sulfhydryl group donor, conjugating N-acetyl-p-benzoquinoneimine (NAPQI) into a nontoxic metabolite, and blunting the hepatocellular toxicity of NAPQI 1.

Indications for Acetylcysteine

• Treatment of acetaminophen overdose with possible or probable risk for hepatotoxicity, ideally administered within 8 to 10 hours postingestion 1.
• Not recommended for patients with no risk for hepatotoxicity as determined by the Rumack-Matthew nomogram 1.
• Patients with delayed presentation, unknown time or duration of ingestion, ingestion of extended-release preparation, or repeated supratherapeutic ingestion cannot be risk stratified with the nomogram and may require NAC treatment based on clinical judgment 1.

Administration of Acetylcysteine

• Typically administered as a 21-hour intravenous protocol with a loading dose, followed by maintenance doses, although specific protocols may vary.
• The use of acetylcysteine in other conditions, such as respiratory diseases or prevention of contrast-induced nephropathy, may follow different administration guidelines but is not directly related to the primary indication for acetaminophen overdose treatment.

Given the critical nature of acetaminophen overdose and the potential for severe hepatotoxicity, the decision to administer acetylcysteine should be based on the most recent and highest quality evidence, prioritizing the reduction of morbidity, mortality, and improvement of quality of life. In clinical practice, this means adhering to established guidelines, such as those recommending NAC for patients at risk of hepatotoxicity from acetaminophen overdose, as outlined in the clinical policy for the management of patients presenting to the emergency department with acetaminophen overdose 1.

From the FDA Drug Label

Acetylcysteine solution, administered orally, is indicated as an antidote to prevent or lessen hepatic injury which may occur following the ingestion of a potentially hepatotoxic quantity of acetaminophen. Acetylcysteine solution, USP is indicated as adjuvant therapy for patients with abnormal, viscid, or inspissated mucous secretions in such conditions as: Chronic bronchopulmonary disease (chronic emphysema, emphysema with bronchitis, chronic asthmatic bronchitis, tuberculosis, bronchiectasis and primary amyloidosis of the lung) Acute bronchopulmonary disease (pneumonia, bronchitis, tracheobronchitis) Pulmonary complications of cystic fibrosis Tracheostomy care Pulmonary complications associated with surgery Use during anesthesia Post-traumatic chest conditions Atelectasis due to mucous obstruction Diagnostic bronchial studies (bronchograms, bronchospirometry, and bronchial wedge catheterization)

The indications for acetylcysteine are:

• Antidote for acetaminophen overdose: to prevent or lessen hepatic injury following the ingestion of a potentially hepatotoxic quantity of acetaminophen 2
• Adjuvant therapy for abnormal mucous secretions: in conditions such as chronic bronchopulmonary disease, acute bronchopulmonary disease, pulmonary complications of cystic fibrosis, and others 2

From the Research

Indications for Acetylcysteine

The indications for acetylcysteine are primarily focused on the treatment of acetaminophen (paracetamol) poisoning. Key points to consider include:

• Acetylcysteine is an effective antidote for paracetamol poisoning, with different treatment criteria existing internationally 3.
• In the UK, acetylcysteine is indicated by paracetamol concentrations higher than the Prescott nomogram or higher than 50% of the nomogram in patients with increased susceptibility to liver toxicity 3.
• The USA uses a single '150-line' nomogram, which removes the need for additional clinical risk assessment, an approach also adopted in Australia, New Zealand, and elsewhere 3.
• Acetylcysteine can lead to irreversible liver damage and even death in acute overdose if not treated promptly 4.
• The US Food and Drug Administration has approved an intravenous formulation of N-acetylcysteine, allowing treatment time to be decreased from 72 hours to 20 hours 4.

Treatment Approaches

Different treatment approaches for acetaminophen poisoning using acetylcysteine include:

• Oral and intravenous (i.v.) acetylcysteine, which appear to be equally effective when given within 8-10 hours of acetaminophen overdose 5.
• i.v. acetylcysteine should be administered when patients are treated more than 10 hours postingestion of acetaminophen overdose or have underlying conditions preventing oral treatment 5.
• A two-bag N-acetylcysteine dosing regimen compared to the traditional three-bag protocol may be associated with lower anaphylactic reactions and gastrointestinal symptoms 6.
• Standard intravenous NAC dosing of 300 mg/kg over 21 hours can prevent hepatotoxicity in patients with massive acetaminophen overdose if received within 8 hours 7.

Patient Considerations

When considering acetylcysteine treatment, the following patient factors are important:

• Individual susceptibility to liver toxicity 3, 5.
• Severity of acetaminophen toxicity 5.
• Time interval between acetaminophen ingestion and initiation of acetylcysteine therapy 5, 7.
• Presence of asthma or atopic histories, where oral acetylcysteine may be preferred 5.