Canadian antidote guide

Acetylcysteine

• N - acetylcysteine
• NAC
• Mucomyst®
• Parvolex®

To prevent hepatotoxicity following the ingestion of a potentially toxic dose of acetaminophen:

• For patients presenting within 24 hours after a single ingestion of acetaminophen (one or many doses taken within a period of 8h or less is considered a single ingestion), the following ingestions may be toxic:
  • Greater than or equal to 200 mg/kg or 10 g,
  • If serum acetaminophen concentration results can be obtained within 8 hours following the ingestion, wait for the results and then plot the results on the Rumack-Matthew Nomogram (Rumack-Matthew International System of units; mcmol/L) (Rumack-Matthew Imperial units; mcg/mL). If the result falls within the possible hepatotoxic zone, start NAC,
  • If serum acetaminophen concentration results can only be obtained 8 hours or more following the ingestion, start NAC while waiting for the results and refer to the Rumack-Matthew Nomogram (Rumack-Matthew International System of units; mcmol/L) (Rumack-Matthew Imperial units; mcg/mL) when the results are available. If the result IS NOT within the possible hepatotoxic zone, stop NAC.
  • Consult the Rumack-Matthew Nomogram (Rumack-Matthew International System of units; mcmol/L) (Rumack-Matthew Imperial units; mcg/mL)
  • If serum acetaminophen concentrations cannot be performed, treat with NAC.
  • If the time of ingestion is unknown, if it is a staggered or a supratherapeutic ingestion, it is advised to consult your poison centre.
• On a case-by-case basis, after consulting with your poison centre for intravenous acetaminophen overdose and for other hepatotoxic substances, such as, carbon tetrachloride, amatoxin-containing mushrooms, pennyroyal oil and others.

To access the N-acetylcysteine protocol, click on the link for your poison center :

• Quebec Poison Centre

Anaphylactoid reaction:

• Cutaneous reaction:
  • Flushing:
    • Reassess NAC indication and continue NAC at the same infusion rate, if necessary.
  • Urticaria:
    • Reassess NAC indication and continue NAC at the same infusion rate, if necessary.
    • Treat with antihistamine.
  • Angioedema:
    • Stop NAC.
    • Treat with antihistamine.
    • Reassess NAC indication. When reaction is under control, continue NAC 1 hour later at the same infusion rate.
• Respiratory and Circulatory symptoms:
  • Dyspnea or hypotension:
    • Stop NAC.
    • Use ABC management; treat symptomatically, such as use of epinephrine.
    • Treat with antihistamine.
    • When patient is stabilized, reassess NAC indication and restart NAC 1 hour later at the same infusion rate.
    • Corticosteroids are not indicated.

NAC overdose:

• Anaphylactoid reaction, hemodilution, seizures, cerebral edema, risk of death.

Other:

• NAC can increase the INR to 1.5 to 2.0
• NAC may interfere with some capillary blood glucose measurement.

• Serum acetaminophen concentration.
• Hepatic workup: AST/ALT, INR (Increase in AST generally comes sooner, but ALT is more useful for monitoring hepatotoxicity). 
• Adverse effects (especially with the first infusion)
• Consult your poison centre for an interpretation of acetaminophen concentration results in the following cases: 
  • Concomitant ingestion of agents that could prolong the absorption phase of acetaminophen
  • Ingestion of extended-release acetaminophen
  • Ingestion of a massive dose of acetaminophen
  • Repeated supratherapeutic ingestions
  • Reduced or absent peristalsis

• Treatment can be temporarily interrupted in the event of an anaphylactoid reaction. See Adverse effects section for more details.
• Acetaminophen overdose:
  • Single ingestion
    • NAC started 4 - 24 h after a single ingestion:
      • Stop NAC immediately if the acetaminophen concentration is not hepatotoxic based on the Rumack-Matthew Nomogram (Rumack-Matthew International System of units; mcmol/L) (Rumack-Matthew Imperial units; mcg/mL).
    • Otherwise,
      • Stop NAC at the end of the 21-hour treatment if, at that time;
        • Acetaminophen concentration is less than 66 mcmol/L and,
        • INR is less than 2 and,
        • AST/ALT normal for patient, or if elevated have decreased by 25% to 50% from peak. 
    • If the end of treatment criteria are not met, continue the ongoing perfusion and contact your poison centre.

Intravenous Route (IV)

• Direct IV: Not recommended
• Continuous IV infusion: Dilute each dose in a compatible solution. Administration is divided into distinct doses according to a predefined protocol and infused using a volumetric pump.
• WARNING: In certain exceptional cases, your poison centre may recommend doubling the infusion. In such cases, make sure to double the concentration of the solution, not the infusion rate.

Enteral Route (PO or NG Tube)

• Possible alternative to IV route. Consult your poison centre to confirm indication and dose of NAC by enteral route.
• Administration of a final solution greater than 5% not recommended due to risk of gastrointestinal irritation.
• PO
  • Dilute injectable formulation (20%; 200 mg/ml) with carbonated citrus or cola beverage in order to obtain a final solution with a 5% concentration (50 mg/ml).
• NG Tube
  • Dilute injectable formulation (20%: 200 mg/ml) with sterile water or water for irrigation in order to obtain a final solution with a 5% concentration (50 mg/ml).

Subcutaneous Route

• Do not use this route.

Intramuscular Route

• Do not use this route.

Intraosseous Route (IO)

• No data available.

Compatibility

Partial list only. Consult the pharmacist on duty at your health care facility.

• Compatible solutions: D5W (preferred), ½NS, NS, sterile water for injection.
• Y-site compatibility: No data available.
• Y-site incompatibility: cefepime, ceftazidime.

Stability

• Unopened vials must be stored at room temperature between 15°C and 30°C.
• Vials that have been opened but not reconstituted are stable for 96 hours in the refrigerator.
• The solution is stable for at least 72 hours at room temperature when reconstituted with D5W, 1/2NS and NS (in PVC container) at a final concentration equal or inferior to 60 mg/ml. 

• Acetylcysteine, 200 mg/ml inj. sol., 10 ml and 30 ml per vial, Hikma, DIN 02459906
• Acetylcysteine, 200 mg/ml inj. sol., 10 ml and 30 ml per vial, Sandoz DIN 02243098

• 21,000 mg to 60,000mg according to the protocol used.

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