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

  • 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) [1] [2]
  • Be aware NAC treatment may affect PT. May see a dose-dependent increase in PT following NAC in patients without hepatotoxicity. [3]

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. [4]
    • 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. [5]
  • Anaphylaxis responds to standard therapies and can usually restart NAC without safely without complications. [6]
    • 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[7]

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

References

  1. Keays R, Harrison PM, Wendon JA, et al. Intravenous acetylcysteine in paracetamol-induced fulminant hepatic failure: a prospective controlled trial. BMJ. 1991;303(6809):1026-1029. (Prospective randomized controlled trial; 50 patients)
  2. Harrison PM, Keays R, Bray GP, et al. Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of N-acetylcysteine. Lancet. 1990;335(8705):1572- 1573. (Retrospective analysis; 100 patients)
  3. Wasserman GS, Garg U. Intravenous administration of Nacetylcysteine: interference with coagulopathy testing. Ann Emerg Med. 2004;44(5):546-547. (Letter)
  4. Heard KJ. Acetylcysteine for acetaminophen poisoning. N Eng J Med. 2008;359(3):285-292. (Review)
  5. http://journals.lww.com/em-news/Fulltext/2012/02000/Toxicology_Rounds__Lessons_from_the_Courtroom_.9.aspx
  6. Sandilands EA, Bateman DN. Adverse reactions associated with acetylcysteine. Clin Toxicol (Phila). 2009;47(2):81-88. (Systematic literature review)
  7. Heard KJ. Acetylcysteine for acetaminophen poisoning. N Engl J Med. 2008; 359(3): 285-92.