N-Acetylcysteine

General

N-acetylcysteine (NAC) prevents toxicity by limiting the formation of NAPQI which increases the ability to detoxify the NAPQI that is formed via hepatotoxic substances such as tylenol.

• Type: Antioxidant
• Dosage Forms:, IV, PO
• Common Trade Names: NAC;

Adult Dosing

Acetaminophen (tylenol) toxicity

PO

• Less preferred than IV route due to unpleasant taste and smell
• 140 mg/kg PO load
• 70 mg/kg PO q4hr x17 doses additional; dilute to 5% soln

IV

• Loading dose: 150mg/kg in 100 mL D5W over 60min
• Second (maintenance) dose: 50mg/kg in 250 mL D5W over 4hr
• Third dose: 100mg/kg in 500 mL D5W over 16hr

Comments

• Almost 100% effective if given <8 hr post-ingestion; less effective if 16-24 hr post-ingestion
• May still be useful >24 hr post-ingestion, even with fulminant hepatic failure. Give NAC until LFTs improve (not until APAP level is 0)
• Be aware NAC treatment may affect PT. May see a dose-dependent increase in PT following NAC in patients without hepatotoxicity.

Pediatric Dosing

IV

for pediatrics (0-18) the addition of a dilution of NAC should be followed to avoid electrolyte and fluid problems 5 to 20 kg:

• Loading Dose: 150 mg/kg in 3 mL/kg diluent, infused over 1 hour
• Second Dose: 50 mg/kg in 7 mL/kg diluent, infused over 4 hours
• Third Dose: 100 mg/kg in 14 mL/kg diluent, infused over 16 hours

21 to 40 kg:

• Loading Dose: 150 mg/kg in 100 mL diluent, infused over 1 hour
• Second Dose: 50 mg/kg in 250 mL diluent, infused over 4 hours
• Third Dose: 100 mg/kg in 500 mL diluent, infused over 16 hours

Over 100 kg:

• Loading Dose: 15,000 mg in 200 mL diluent, infused over 1 hour
• Second Dose: 5,000 mg in 500 mL diluent, infused over 4 hours
• Third Dose: 10,000 mg in 1,000 mL diluent, infused over 16 hours

Special Populations

• Pregnancy Rating:
• Both IV or oral NAC may be used in pregnant patients with Acetaminophen toxicity.
  • IV formulation may be preferred to increase fetal NAC concentrations

• Lactation:
• Renal Dosing
  • Adult
  • Pediatric
• Hepatic Dosing
  • Adult
  • Pediatric

Contraindications

• Allergy to class/drug

Adverse Reactions

Serious

• Anaphylactoid reaction but also associated with seizures, cerebral edema, & herniation.
• Anaphylaxis responds to standard therapies and can usually restart NAC without safely without complications.
  • No treatment is necessary for isolated flushing
  • If urticaria, then Diphenhydramine
  • If angioedema, bronchospasm, or hypotension, then Diphenhydramine, corticosteroids, and bronchodilators along with cessation of the NAC
    • Restart NAC infusion at a slower rate 1 hour after administration of medical therapy
  • Epinephrine is not recommended although it can be used in patients with severe progressive symptoms

Common

• sulfur-smell causes nausea and vomiting. Consider mixing with juice or soda, in a cup with a lid and straw

Pharmacology

• Half-life:
• Metabolism:
• Excretion:
• Mechanism of Action:
  • Intravenous acetylcysteine is indicated for the treatment of acetaminophen overdose by preventing depletion of glutathione reserves.

See Also

• Acetaminophen (tylenol) toxicity