What is the treatment for an acetaminophen (Tylenol) overdose?

Treatment of Acetaminophen (Tylenol) Overdose

Immediately administer N-acetylcysteine (NAC) to all patients with acetaminophen levels above the treatment line on the Rumack-Matthew nomogram or to any patient with suspected overdose who has elevated transaminases (AST/ALT >1,000 IU/L), ideally within 8 hours of ingestion to prevent severe hepatotoxicity and death. 1

Immediate Assessment and Risk Stratification

Obtain Acetaminophen Level and Timing

• Draw acetaminophen level at 4 hours post-ingestion or later—levels drawn before 4 hours are unreliable and must be repeated at 4 hours 1
• Use the Rumack-Matthew nomogram to assess risk: levels above 200 mcg/mL at 4 hours or 50 mcg/mL at 12 hours indicate potential hepatotoxicity 1
• For extended-release formulations, obtain at least one additional acetaminophen level 4-6 hours after the first measurement, as absorption may be delayed beyond 8 hours 2

Baseline Laboratory Testing

• Order immediately: AST, ALT, INR, creatinine, BUN, electrolytes, and blood glucose 3
• Very high aminotransferases (AST/ALT >3,500 IU/L) are highly correlated with acetaminophen poisoning even without clear overdose history 1, 3

N-Acetylcysteine (NAC) Treatment Protocol

Indications for NAC Treatment

• Any acetaminophen level above the treatment line on the Rumack-Matthew nomogram 1
• Any suspected acetaminophen ingestion with AST/ALT >1,000 IU/L, regardless of acetaminophen level 1
• Repeated supratherapeutic ingestion (RSTI) with any elevation in transaminases 1

NAC Dosing Regimen

• Loading dose: 150 mg/kg IV over 60 minutes (not 15 minutes, to reduce hypersensitivity reactions) 4
• Second dose: 50 mg/kg IV over 4 hours 4
• Third dose: 100 mg/kg IV over 16 hours 4
• Total treatment duration: 20-21 hours for standard protocol 4, though 48-hour protocols may be considered for delayed presentations 5

Critical Timing Considerations

• Treatment within 8 hours: Only 2.9-4% develop severe hepatotoxicity 1, 4
• Treatment within 10 hours: 6.1% develop severe hepatotoxicity 1
• Treatment 10-24 hours post-ingestion: 26.4% develop severe hepatotoxicity 1
• Treatment after 15-24 hours: 44% develop hepatotoxicity 4
• Even late treatment (>24 hours) remains beneficial, though significantly less effective 1

Serial Monitoring During Treatment

• Monitor AST, ALT, and INR every 4 hours until aminotransferases peak and begin declining 3
• INR monitoring every 4 hours identifies evolving coagulopathy, which predicts severe hepatotoxicity 3
• If acute liver failure develops, add phosphate monitoring as hypophosphatemia is common in severe cases 3

Special Populations and Scenarios

Repeated Supratherapeutic Ingestion (RSTI)

• RSTI with AST <50 IU/L: Treat with NAC; no progression to hepatotoxicity expected 1
• RSTI with AST 50-1,000 IU/L: Treat with NAC; 15% develop hepatotoxicity, 2% mortality 1
• RSTI with AST >1,000 IU/L: Treat with NAC; 14% mortality 1

High-Risk Patients

• Patients with pre-existing liver disease, chronic alcohol use, or cirrhosis may develop toxicity at lower thresholds and should receive NAC treatment with lower thresholds for intervention 1
• For chronic alcoholics, severe hepatotoxicity has been documented with doses as low as 4-5 g/day 1

Extended-Release Formulations

• Obtain serial acetaminophen levels, as drug absorption may continue beyond 8-14 hours post-ingestion 2
• A single 4-hour level may miss patients with delayed absorption who later develop toxic levels 2
• Initiate NAC if either level is above the nomogram line 2

Common Pitfalls to Avoid

• Do not rely on a single early acetaminophen level (<4 hours)—it is unreliable 1
• Low or absent acetaminophen levels do not rule out poisoning if ingestion was remote, occurred over several days, or timing is uncertain 1
• Do not delay NAC while waiting for levels if there is high clinical suspicion with elevated transaminases 1
• Be aware of combination products containing acetaminophen (with opioids like hydrocodone or codeine), which significantly increase risk of unintentional overdose 1
• Standard NAC courses may need extension in patients with persistently elevated acetaminophen levels or ongoing hepatic injury 6, 7

Hypersensitivity Reactions to NAC

• Hypersensitivity reactions (hypotension, wheezing, shortness of breath, bronchospasm) may occur during NAC infusion, particularly with rapid loading doses 4
• Using a 60-minute infusion for the loading dose (rather than 15 minutes) reduces hypersensitivity reaction rates 4
• Most reactions are transient skin erythema or mild urticaria that do not require discontinuation of therapy 5