Uses of Acetylcysteine
Acetylcysteine has multiple established clinical uses, with its primary indications being as an antidote for acetaminophen overdose and as a mucolytic agent for respiratory conditions with abnormal or viscid mucous secretions. 1, 2
Primary Indications
1. Acetaminophen Overdose
- Acetylcysteine is the definitive treatment for acetaminophen-induced hepatotoxicity 1
- Significantly reduces:
- Hepatotoxicity (18% vs 58%)
- Mortality (0.7% vs 6%)
- Cerebral edema (40% vs 68%)
- Need for vasopressors (48% vs 80%)
- Treatment should be initiated as soon as possible after overdose, without waiting for serum acetaminophen level results 1
- The Rumack-Matthew nomogram should be used to stratify risk when time of ingestion is known 1
2. Respiratory Conditions
- Indicated as adjuvant therapy for patients with abnormal, viscid, or inspissated mucous secretions in: 2
- Chronic bronchopulmonary diseases (chronic emphysema, emphysema with bronchitis, chronic asthmatic bronchitis)
- Acute bronchopulmonary diseases (pneumonia, bronchitis, tracheobronchitis)
- Pulmonary complications of cystic fibrosis
- Tracheostomy care
- Pulmonary complications associated with surgery
- Post-traumatic chest conditions
- Atelectasis due to mucous obstruction
- For COPD patients with moderate to severe COPD and a history of two or more exacerbations in the previous 2 years, oral N-acetylcysteine is recommended to prevent acute exacerbations 3
- The American Thoracic Society and European Respiratory Society conditionally recommend mucolytic therapy (including N-acetylcysteine) for COPD patients with moderate to severe airflow obstruction and exacerbations despite optimal inhaled therapy 1
- Most effective dose for COPD patients is 600 mg twice daily 1
Additional Uses
1. Non-Acetaminophen Acute Liver Failure
- May benefit patients with acute liver failure not related to acetaminophen 1
- Meta-analyses show improvements in:
- Liver transplant-free survival (64% vs 26%)
- Overall survival (76% vs 59%)
- Patients with grade I-II hepatic encephalopathy show the greatest benefit 1
2. Diagnostic Procedures
- Used in diagnostic bronchial studies: 2
- Bronchograms
- Bronchospirometry
- Bronchial wedge catheterization
3. Other Applications
- Acts as a free-radical scavenger due to its role as a precursor of glutathione 4, 5
- Has been investigated for use in:
Pharmacokinetics and Administration
- After oral dose of 200-400 mg, peak plasma concentration of 0.35-4 mg/L is achieved within 1-2 hours 7
- Volume of distribution ranges from 0.33 to 0.47 L/kg with approximately 50% protein binding 7
- Terminal half-life of 6.25 hours following oral administration 7
- Primarily metabolized and incorporated into proteins, with inorganic sulfate as the major excretory product 7
Safety Profile and Monitoring
- Common side effects include: 1
- Nausea, vomiting, diarrhea or constipation
- Skin rash (<5%)
- Transient bronchospasm (1-2%)
- Generally has a favorable safety profile even when combined with other treatments 1
- Charcoal may interfere with drug absorption (up to 96% adsorption) 7
Clinical Considerations
- For COPD patients, N-acetylcysteine should be considered when patients continue to have exacerbations despite maximal inhaled therapy 3
- The interval between acetaminophen ingestion and treatment with acetylcysteine is closely related to outcome, emphasizing the importance of prompt treatment 1
- Some older studies show limited efficacy for mucolytic effects in certain populations 8, but more recent guidelines support its use in specific COPD populations 3, 1