N-Acetylcysteine
General
Acetylcysteine, or N-acetylcysteine (NAC), is a medication that is used to treat acetaminophen overdose. It can also be used as a nebulized medication to help loosen thick pulmonary sections.
When acetaminophen is taken in large doses, a toxic metabolite N-acetyl-pbenzoquinone imine (NAPQI) accumulates in the body. NAC helps to replete glutathione reserves in the liver, which helps the liver prevent damage from the hepatotoxic NAPQI metabolite.
- Type: Antioxidant, antidote
- Dosage Forms:, IV, PO, Nebulized
- 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) [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: B
- 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:
- Unknown if excreted in breast milk
- Renal Dosing
- Adult
- Not defined
- Pediatric
- Not defined
- Adult
- Hepatic Dosing
- Adult
- Not defined
- Pediatric
- Not defined
- Adult
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 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[8]
- 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
References
- ↑ 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)
- ↑ 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)
- ↑ Wasserman GS, Garg U. Intravenous administration of Nacetylcysteine: interference with coagulopathy testing. Ann Emerg Med. 2004;44(5):546-547. (Letter)
- ↑ Heard KJ. Acetylcysteine for acetaminophen poisoning. N Eng J Med. 2008;359(3):285-292. (Review)
- ↑ http://journals.lww.com/em-news/Fulltext/2012/02000/Toxicology_Rounds__Lessons_from_the_Courtroom_.9.aspx
- ↑ Sandilands EA, Bateman DN. Adverse reactions associated with acetylcysteine. Clin Toxicol (Phila). 2009;47(2):81-88. (Systematic literature review)
- ↑ Heard KJ. Acetylcysteine for acetaminophen poisoning. N Engl J Med. 2008; 359(3): 285-92.
- ↑ Acetylcysteine: Drug information. UpToDate. www.uptodate.com. Accessed April 2, 2019.