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 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

Acetaminophen toxicity

For children there is a diluent added to the NAC so that there is no electrolyte and volume complications.

PO

• 140 mg/kg body weight, orally, once as a loading dose
• Maintenance Dose: 70 mg/kg body weight, orally, 4 hours after the loading dose and every 4 hours for 17 total doses, unless repeated acetaminophen assays reveal nontoxic levels

100 to 109 kg:

• Loading dose: 15 g (75 mL) in 225 mL diluent; total volume: 300 mL
• Maintenance Dose: 7.5 g (37 mL) in 113 mL diluent; total volume: 150 mL

90 to 99 kg:

• Loading dose: 14 g (70 mL) in 210 mL diluent; total volume: 280 mL
• Maintenance Dose: 7 g (35 mL) in 105 mL diluent; total volume: 140 mL

80 to 89 kg

• Loading dose: 13 g (65 mL) in 195 mL diluent; total volume: 260 mL
• Maintenance Dose: 6.5 g (33 mL) in 97 mL diluent; total volume: 130 mL

70 to 79 kg

• Loading dose: 11 g (55 mL) in 165 mL in diluent; total volume: 220 mL
• Maintenance Dose: 5.5 g (28 mL) in 82 mL diluent; total volume: 110 mL

60 to 69 kg

• Loading dose: 10 g (50 mL) in 150 mL diluent; total volume: 200 mL
• Maintenance Dose: 5 g (25 mL) in 75 mL diluent; total volume: 100 mL

50 to 59 kg

• Loading dose: 8 g (40 mL) in 120 mL diluent; total volume: 160 mL
• Maintenance Dose: 4 g (20 mL) in 60 mL diluent; total volume: 80 mL

40 to 49 kg

• Loading dose: 7 g (35 mL) in 105 mL diluent; total volume: 140 mL
• Maintenance Dose: 3.5 g (18 mL) in 52 mL diluent; total volume: 70 mL

30 to 39 kg

• Loading dose: 6 g (30 mL) in 90 mL diluent; total volume: 120 mL
• Maintenance Dose: 3 g (15 mL) in 45 mL diluent; total volume: 60 mL

20 to 29 kg

• Loading dose: 4 g (20 mL) in 60 mL diluent; total volume: 80 mL
• Maintenance Dose: 2 g (10 mL) in 30 mL diluent; total volume: 40 mL

Less than 20 kg

• Add 3 mL of diluent to each 1 mL (200 mg) of 20% acetylcysteine solution
• Loading dose: 140 g/kg
• Maintenance Dose: 70 g/kg

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:
  • Unknown if excreted in breast milk
• Renal Dosing
  • Adult
    • Not defined
  • Pediatric
    • Not defined
• Hepatic Dosing
  • Adult
    • Not defined
  • Pediatric
    • Not defined

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:
  • Reduced acetylcysteine: 2 hours
  • Total acetylcysteine: Adults: 5.6 hours, Newborns: 11 hours
• Metabolism:
• Excretion:
  • Urine (13 - 38%)
• Mechanism of Action:
  • Intravenous acetylcysteine is indicated for the treatment of acetaminophen overdose by preventing depletion of glutathione reserves.

See Also

• Acetaminophen (tylenol) toxicity