Acetaminophen Overdose and NAC Dosing

• Early administration of NAC (<8 hours post-ingestion) is vital to decreasing the risk of hepatotoxicity; acetaminophen is a leading cause of drug-induced liver injury.
• Acetaminophen is widely available in prescription and over-the-counter medications, either as single agent or combination products (e.g. dextromethorphan, opioids, diphenhydrAMINE).
• Maintain a strong index of suspicion for acetaminophen toxicity in all patients with intentional drug overdose and those with therapeutic misadventures (e.g. taking excessive amounts of a single product, or using recommended doses of several different acetaminophen containing products).

If known time of ingestion

• Obtain acetaminophen concentration at 4 hours post-ingestion or as soon as possible thereafter.
• Plot acetaminophen concentration on Rumack-Matthew nomogram (see above).
• If above “treatment line” (line connecting 150 µg/mL (993 µmol/L) at 4 hours and 4.7 µg/mL (31 µmol/L) at 24 hours), NAC is indicated.

Unknown time of ingestion

• Determine earliest possible time of ingestion:
  • If <24 hours post-ingestion, plot on Rumack-Matthew nomogram and initiate NAC if above “treatment line.”
• If earliest time of ingestion cannot be estimated, treatment with NAC is indicated if:
  • Detectable acetaminophen concentration.
  • Abnormal aminotransferases (AST or ALT).

Extended release formulations/coingestions of opioids, anticholinergics, or other medications that will slow gut motility

• Obtain initial 4 hour post-ingestion acetaminophen concentration.
  • If above treatment line, NAC is indicated.*
  • If below treatment line, repeat acetaminophen concentration at 6 to 7 hours post-ingestion.
    • If above treatment line, NAC should be initiated within 8 hours post-ingestion.

Chronic acetaminophen ingestion

• Patients taking repeated, supratherapeutic (>4 g/day) acetaminophen ingestions.
  • Treatment with NAC indicated if:
    • Detectable acetaminophen concentration.
    • Abnormal aminotransferases (AST or ALT).

Serum acetaminophen concentration should be sent in all patients presenting with intentional overdose or those using excessive amounts of acetaminophen containing products.

NAC treatment should be initiated within 8 hours post-ingestion to decrease risk of hepatotoxicity.