What are the indications for N-acetyl cysteine (NAC) injection?

N-Acetylcysteine Injection Indications

N-acetylcysteine (NAC) injection is primarily indicated for the treatment of acetaminophen overdose to prevent or lessen hepatic injury, and should be administered as soon as possible after overdose and within 24 hours of ingestion. 1

Primary Indications for NAC Injection

• Acetaminophen Overdose

  • For known or suspected acute acetaminophen overdose with serum levels plotting in the possible or probable risk zones on the Rumack-Matthew nomogram 2
  • For acetaminophen overdose presenting >24 hours after ingestion when the nomogram cannot be used 2
  • For cases with unknown time or unreliable history of ingestion 3
  • For extended-release or repeated supratherapeutic ingestions of acetaminophen 3

• Acetaminophen-Associated Acute Liver Failure

  • Strongly recommended by the American Gastroenterological Association for patients with acetaminophen-associated acute liver failure 3
  • For cases of acute liver failure where acetaminophen ingestion is suspected or possible, even without confirmatory history 2

Timing and Administration

• NAC should be initiated as soon as possible after acetaminophen overdose, ideally within 8-10 hours of ingestion 2
• Treatment may still provide benefit when started up to 24 hours after ingestion, though efficacy decreases with time 2, 4
• For intravenous administration, the recommended regimen is:
  • 150 mg/kg loading dose over 15 minutes
  • Followed by 50 mg/kg over 4 hours
  • Then 100 mg/kg over 16 hours 2, 1

Special Considerations

• Patients at increased risk for acetaminophen toxicity (alcoholics, fasting patients) may develop toxicity at lower doses and should receive NAC even if acetaminophen levels are below the typical treatment threshold 2
• Very high aminotransferases are highly correlated with acetaminophen poisoning and should prompt consideration of NAC even without confirmatory history 2
• For massive acetaminophen overdose with concentrations above the "300-line," increased NAC dosing may be beneficial 5
• The 21-hour intravenous protocol is often too short for optimal treatment, particularly in severe cases 6

Mucolytic Indications (Secondary Use)

NAC is also indicated as a mucolytic agent for patients with abnormal, viscid, or inspissated mucous secretions in conditions such as:

• Chronic bronchopulmonary disease (chronic emphysema, emphysema with bronchitis, chronic asthmatic bronchitis, tuberculosis, bronchiectasis) 1
• Acute bronchopulmonary disease (pneumonia, bronchitis, tracheobronchitis) 1
• Pulmonary complications of cystic fibrosis 1
• Tracheostomy care 1
• Pulmonary complications associated with surgery 1
• Atelectasis due to mucous obstruction 1
• Diagnostic bronchial studies 1

Contraindications and Adverse Effects

• There are no contraindications to NAC administration for acetaminophen overdose 1
• Intravenous NAC may cause anaphylactic reactions 7
• When used as a mucolytic, NAC is contraindicated in patients who are sensitive to it 1
• Asthmatics under treatment with NAC should be watched carefully for bronchospasm 1

Efficacy and Outcomes

• When given within eight hours of acetaminophen ingestion, NAC is protective regardless of the initial plasma acetaminophen concentration 4
• Hepatotoxicity develops in only 6.1% of patients at probable risk when NAC is started within 10 hours of acetaminophen ingestion, compared to 26.4% when therapy is begun 10-24 hours after ingestion 4
• With appropriate NAC therapy, mortality from acetaminophen overdose is rare 8