What are the uses and dosages of N-acetyl cysteine (NAC)?

N-Acetylcysteine (NAC): Uses and Dosages

N-acetylcysteine (NAC) is primarily used as an antidote for acetaminophen overdose and as a mucolytic agent, with specific FDA-approved dosing regimens for each indication. 1, 2

Acetaminophen Overdose Treatment

Oral Administration Protocol

• Loading dose: 140 mg/kg body weight 1, 2
• First maintenance dose: 70 mg/kg given 4 hours after loading dose 2
• Subsequent maintenance doses: 70 mg/kg every 4 hours for a total of 17 doses 1, 2

Intravenous Administration Protocol

• Loading dose: 150 mg/kg over 15-60 minutes 1
• First maintenance dose: 50 mg/kg over 4 hours 1
• Second maintenance dose: 100 mg/kg over 16 hours 1

Key Clinical Considerations for Acetaminophen Overdose

• Treatment should be initiated as soon as possible, ideally within 8 hours of ingestion, but can be beneficial up to 24 hours post-ingestion 3
• For massive overdose (>30g or >500 mg/kg), consider increased NAC dosing beyond standard protocol if evidence of ongoing liver injury persists 1
• The oral NAC protocol may preserve more hepatocytes than the 21-hour IV protocol for patients presenting within 24 hours of ingestion 4
• Monitor for NAC-related adverse effects, particularly hypersensitivity reactions (10-15% of patients) 1
• Continue NAC treatment until:
  • Acetaminophen levels are undetectable
  • Liver enzymes are decreasing
  • PT/INR is improving
  • Patient is clinically improving

Mucolytic Therapy

Nebulization (Face Mask, Mouthpiece, Tracheostomy)

• 1-10 mL of 20% solution or 2-20 mL of 10% solution every 2-6 hours 2
• Recommended dose: 3-5 mL of 20% solution or 6-10 mL of 10% solution 3-4 times daily 2

Direct Instillation

• 1-2 mL of 10-20% solution as often as every hour 2
• For tracheostomy care: 1-2 mL of 10-20% solution every 1-4 hours 2

Diagnostic Bronchograms

• 2-3 administrations of 1-2 mL of 20% solution or 2-4 mL of 10% solution by nebulization or intratracheal instillation prior to procedure 2

Adverse Effects and Precautions

Common Adverse Effects

• Oral administration: Nausea, vomiting, gastrointestinal symptoms 2
• IV administration: Hypersensitivity reactions, anaphylaxis (10-15% of patients) 1
• Nebulization: Stomatitis, rhinorrhea, drowsiness, chest tightness, bronchospasm 2

Monitoring and Management

• For IV administration, monitor for hypersensitivity reactions; manage with temporary discontinuation, antihistamines, and slower infusion rate when restarting 1
• For oral administration in acetaminophen overdose, dilution minimizes the propensity to aggravate vomiting 2
• NAC solution does not contain antimicrobial agents; unused portions should be refrigerated and used within 96 hours 2

Special Considerations

• NAC is pregnancy category B; no evidence of teratogenic effects in animal studies 2
• For patients with hepatic encephalopathy, consider discontinuing NAC to avoid further administration of nitrogenous substances 2
• Patients at risk of gastric hemorrhage should be evaluated for risk versus benefit of oral NAC treatment 2
• Certain materials (notably iron, copper, and rubber) react with NAC; use equipment made of glass, plastic, aluminum, anodized aluminum, chromed metal, tantalum, sterling silver, or stainless steel 2

Emerging Uses

While not FDA-approved for these indications, NAC has shown potential benefit in:

• Chronic obstructive pulmonary disease
• Contrast-induced nephropathy prevention
• Various neuropsychiatric conditions (schizophrenia, bipolar disorder, OCD)
• Polycystic ovary disease and male infertility 5

NAC's mechanism of action in these conditions is primarily related to its antioxidant properties and ability to replenish glutathione stores, but these uses require further clinical validation before becoming standard practice.