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N-Acetylcysteine

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N-Acetylcysteine, Acetylcysteine, Acetadote, Mucomyst, Cetylev, NAC, N-Acetylcysteine Protocol for Acetaminophen Toxicity

  • See Also
  1. Acetaminophen Overdose
  2. Mushroom Poisoning
  3. Contrast-Induced Nephropathy
  4. COPD Management
  • Indications
  1. Established Toxicology
    1. Acetaminophen Overdose
    2. Mushroom Poisoning
    3. Heavy Metal Poisoning
      1. Not first-line, but may reduce oxidative stress
    4. Contrast-Induced Nephropathy prevention
      1. Not typically used in U.S. (hydration is used instead)
  2. Controversial Use as Mucolytic in Chronic Lung Disease (conflicting evidence of benefit)
    1. Prevention of COPD Exacerbation
      1. Dose: 600-1200 mg/day in divided dosing
      2. Decramer (2005) Lancet 365(9470):1552-60 [PubMed]
    2. Idiopathic Pulmonary Fibrosis
      1. Dose: 1800 mg/day in divided dosing
      2. Demedts (2005) N Engl J Med 353(21):2229-42 [PubMed]
  • Mechanism
  1. N-Acetylcysteine increases glutathione levels
    1. Acts as detoxification agent
    2. Acts as antioxidant
  2. N-Acetylcysteine increases nitric oxide concentrations
    1. Stimulates vasodilation
  3. N-Acetylcysteine acts as a mucolytic
    1. Cleaves Protein complexes and decreases mucous viscosity
    2. May be effective in Chronic Bronchitis
  1. Protocol
    1. See Acetaminophen Overdose
    2. Directed by Rumack-Matthew Acetaminophen Nomogram
      1. http://www.ars-informatica.ca/toxicity_nomogram.php?calc=acetamin
    3. Continue NAC beyond protocol below if any of the following persist at end of protocol
      1. High Acetaminophen level or
      2. Increasing Bilirubin, INR or transaminases
  2. Formulation
    1. Intravenous indications
      1. Fulminant hepatic failure (best studied)
      2. Pregnancy
      3. Intractable Vomiting
    2. Oral advantages
      1. Preferred route
      2. Cheap and effective
      3. Lower Incidence of anaphylactoid reaction than with IV form
  3. Adults (and children weight >20 kg)
    1. Intravenous (21 hour protocol) - Three bag regimen (standard protocol)
      1. Load: 150 mg/kg in 200 ml D5W IV over 1 hour for 1 dose
      2. Next: 12.5 mg/kg/hour for 4 hours (50 mg/kg in 7 ml/kg up to 500 ml D5W given over 4 hours)
      3. Next: 6.25 mg/kg/hour for 16 hours (100 mg/kg in 14 ml/kg up to 1000 ml D5W given over 16 hours)
        1. May be extended for ongoing hepatotoxicity until Liver Function Tests start improving
      4. Precaution in weight <88 kg (40kg)
        1. Dilute to 40 mg/ml in D5W
        2. Smaller volume to prevent Hyponatremia
    2. Intravenous (20 hour protocol) - Two bag regimen (newer protocol proposed to replace 3 bag regimen)
      1. Load: 200 mg/kg in 500 ml D5W (250 ml D5W if weight 20-50 kg) IV over 4 hours for 1 dose
      2. Next: 100 mg/kg in diluent (14 ml/kg up to 1000 ml D5W) given over 16 hours
      3. Efficacy compared with standard 3 bag regimen
        1. Fewer adverse effects (e.g. anaphylactoid reaction, OR 0.24)
        2. No difference in hepatotoxicity (same efficacy as 3 bag regimen)
        3. Nakatsu (2025) Clin Toxicol 63(3):155-65 +PMID: 40013897 [PubMed]
    3. Oral (72 hour protocol)
      1. Load: 140 mg/kg orally for 1 dose
      2. Next 70 mg/kg every 4 hours for total of 17 doses
      3. Administration pearls
        1. Better tolerated when chilled or mixed with orange juice or soda
        2. NAC smell may decrease tolerability (consider placing in covered cup with straw)
        3. Vomiting
          1. Re-dose if vomits within one hour of dose
            1. No need to re-dose if Vomiting after one hour (Absorbed quickly)
          2. Consider concurrent Ondansetron (Zofran) or other Antiemetic
          3. Consider switching to intravenous NAC
  • Dosing
  • Respiratory Mucolytic
  1. Inconsistent evidence of benefit
  2. Prevention of COPD Exacerbation
    1. Dose: 600-1200 mg/day in divided dosing
    2. Decramer (2005) Lancet 365(9470):1552-60 [PubMed]
  3. Idiopathic Pulmonary Fibrosis
    1. Dose: 1800 mg/day in divided dosing
    2. Demedts (2005) N Engl J Med 353(21):2229-42 [PubMed]
  • Adverse Effects (uncommon at doses 1200 mg/day or less)
  1. Nausea
  2. Vomiting
  3. Diarrhea
  4. Anaphylactoid Reaction (8% with IV)
    1. Typically occurs at 30 to 60 minutes after starting infusion
    2. Stop infusion
    3. Treat reaction
      1. Epinephrine for Anaphylaxis-like symptoms
      2. Diphenhydramine for other allergic symptoms
    4. Restart infusion slowly
      1. Contact poison control for rate adjustment in Acetaminophen Overdose
      2. Stop infusion if anaphylactoid reaction recurs or increases in severity
        1. Discontinue for severe reactions (deaths have occurred)
  • Safety
  1. Pregnancy Category B
  2. Unknown safety in Lactation
  • Resources
  1. N-Acetylcysteine Oral Solution (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=75b48fab-cef6-465c-a1e0-d085b3988bc4
  2. N-Acetylcysteine Injection Solution (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d990ef51-ced2-4359-b99b-092334d2dc9b
  • References
  1. Nordt and Swadron in Majoewsky (2013) EM:Rap 13(4): 10-11
  2. Rowden (2006) Clin Lab Med 26(1): 49-65 [PubMed]
  3. Sung (1997) Pediatrics 100(3 pt 1): 389-91 [PubMed]