What is the antidote for an acetaminophen (Panadol) overdose?

N-Acetylcysteine (NAC) is the Antidote for Panadol (Acetaminophen) Overdose

N-acetylcysteine (NAC) is the specific antidote for acetaminophen (Panadol) overdose and should be administered as soon as possible after ingestion to prevent or lessen hepatic injury. 1, 2

Mechanism of Action

Acetaminophen overdose leads to hepatotoxicity through the following mechanism:

• Normal acetaminophen metabolism occurs primarily through glucuronidation and sulfation pathways
• In overdose, these pathways become saturated
• Increased metabolism via cytochrome P-450 creates a toxic metabolite (NAPQI)
• NAPQI depletes glutathione stores and binds to liver proteins, causing cellular necrosis 1, 2

NAC works by:

• Replenishing glutathione stores
• Providing sulfhydryl groups for detoxification
• Serving as an alternate substrate for conjugation with the toxic metabolite
• Reducing inflammatory response in the liver 1, 2

Treatment Protocol

Administration Routes and Dosing

1. Oral Administration 1, 2:

   • Loading dose: 140 mg/kg diluted to 5% solution
   • Maintenance dose: 70 mg/kg every 4 hours for 17 doses (72-hour protocol)
   • If vomiting occurs within 1 hour of administration, repeat the dose

2. Intravenous Administration 1:

   • Loading dose: 150 mg/kg in 5% dextrose over 15 minutes
   • First maintenance dose: 50 mg/kg over 4 hours
   • Second maintenance dose: 100 mg/kg over 16 hours

Timing of Administration

• Most effective when given within 8 hours of ingestion 3, 4
• Still beneficial when started within 24 hours of ingestion 1, 2
• Treatment should not be delayed while waiting for acetaminophen levels 2

Treatment Decision Algorithm

1. For known time of ingestion within 24 hours:

   • Draw acetaminophen level at least 4 hours post-ingestion
   • Plot level on Rumack-Matthew nomogram
   • If level is above the treatment line or cannot be obtained, administer NAC 1, 2

2. For unknown time of ingestion or presentation >24 hours:

   • Check acetaminophen level and liver function tests
   • If acetaminophen is detectable OR liver enzymes are elevated, administer NAC 1
   • If clinical suspicion for acetaminophen toxicity exists despite negative tests, administer NAC 1

3. For repeated supratherapeutic ingestion:

   • If total dose exceeds 4g/24 hours, check liver function tests
   • If liver enzymes are elevated, administer NAC 1

Additional Management

• For ingestion within 4 hours: Administer activated charcoal (1g/kg orally) before starting NAC 1
• For patients with hepatotoxicity: Continue NAC until:
  • Acetaminophen level is undetectable
  • Liver enzymes are improving
  • Patient is clinically improving 1

Common Pitfalls and Caveats

• Do not delay NAC administration while waiting for acetaminophen levels if overdose is suspected 2
• Do not rely solely on the nomogram for repeated ingestions, extended-release formulations, or delayed presentations 1
• Be aware of NAC side effects:
  • IV administration: anaphylactoid reactions (rash, urticaria, bronchospasm)
  • Oral administration: nausea, vomiting 1, 2
• Low or undetectable acetaminophen levels do not rule out toxicity if presentation is delayed 1
• Risk factors for increased toxicity include malnutrition, chronic alcohol use, and fasting states 1, 2

NAC remains the standard of care for acetaminophen overdose with proven efficacy in reducing morbidity and mortality when administered promptly 3, 4.