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

Treatment of Acetaminophen (Tylenol) Overdose

Administer N-acetylcysteine (NAC) immediately 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, 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 between 4-24 hours post-ingestion for acute single ingestions 2
• Levels drawn before 4 hours are unreliable and should be repeated at 4 hours 1
• Use the Rumack-Matthew nomogram to determine risk: levels above 200 mcg/mL at 4 hours or 50 mcg/mL at 12 hours indicate potential hepatotoxicity 2
• For extended-release formulations, obtain at least two levels 4-6 hours apart, as absorption may be delayed up to 8-14 hours post-ingestion 3

Initial Laboratory Panel

• Order baseline AST, ALT, INR, creatinine, BUN, electrolytes, and blood glucose immediately 4
• Very high aminotransferases (AST/ALT >3,500 IU/L) are highly correlated with acetaminophen poisoning even without clear overdose history 4

N-Acetylcysteine (NAC) Treatment Protocol

Indications for NAC (Level B Recommendation)

Administer NAC to patients with:

• Acetaminophen levels above the treatment line on the Rumack-Matthew nomogram 1
• Any suspected acetaminophen ingestion with elevated transaminases (AST/ALT >1,000 IU/L), regardless of acetaminophen level 1, 4
• Acute ingestions >150 mg/kg or >10 grams in adults 2
• Repeated supratherapeutic ingestions ≥10 grams or 200 mg/kg over 24 hours 2

NAC Dosing Regimen (IV Protocol)

Loading dose: 140 mg/kg IV over 1 hour, followed by 70 mg/kg IV every 4 hours for 12 doses (48-hour protocol) 5

• Alternative 20-hour protocol exists but the 48-hour protocol is superior when treatment is delayed 5
• Must be diluted prior to intravenous use 6

Treatment Timing and Outcomes

• Treatment within 8 hours: Only 2.9% develop severe hepatotoxicity 2
• Treatment within 10 hours: 6.1% develop severe hepatotoxicity; among high-risk patients, only 4.2% develop severe hepatotoxicity 1, 5
• Treatment 10-24 hours: 26.4%-27.1% develop severe hepatotoxicity 2, 5
• Treatment >24 hours: Still beneficial but significantly less effective 1

Do NOT Administer NAC (Level B Recommendation)

• Patients with acetaminophen levels below the treatment line on the nomogram and no evidence of hepatotoxicity 1

Special Populations and Scenarios

Repeated Supratherapeutic Ingestion (RSTI)

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

High-Risk Patients

• Chronic alcoholics: Severe hepatotoxicity documented with doses as low as 4-5 g/day; mortality 20-33% with doses 2.5-16.5 g/day 2
• Pre-existing liver disease: Maximum daily dose should be limited to 2-3 grams 2
• These patients may develop toxicity at lower thresholds 1

Extended-Release Formulations

• Absorption may continue beyond 8 hours post-ingestion 3
• Obtain at least two acetaminophen levels 4-6 hours apart 3
• Initiate NAC if either level is above the nomogram line 3

Monitoring During Treatment

Serial Laboratory Monitoring

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

Extending NAC Treatment

• Standard NAC courses may need extension in patients with persistently elevated acetaminophen levels or ongoing hepatic injury 7, 8

Adjunctive Measures

Gastrointestinal Decontamination

• Activated charcoal should be offered to patients presenting early (within 1-2 hours of ingestion) 8

Critical Pitfalls to Avoid

• Do not rely on a single 4-hour level for extended-release formulations—patients may initially fall below the nomogram line but later rise above it 3
• Low or absent acetaminophen levels do not rule out poisoning if ingestion was remote, occurred over several days, or timing is uncertain 2
• Do not delay NAC while awaiting acetaminophen levels if there is strong suspicion of toxic ingestion with elevated transaminases 1, 4
• Beware of combination products (e.g., with opioids)—patients may not realize they are taking acetaminophen from multiple sources 2

Adverse Reactions to NAC

• Hypersensitivity reactions occur in 14.3% of patients, most commonly transient skin erythema or mild urticaria during loading dose 5
• 91% of reactions do not require discontinuation of therapy 5
• Monitor for hypotension, wheezing, shortness of breath, and bronchospasm 6

Expected Outcomes

• With appropriate NAC treatment, mortality is approximately 1% and serious complications requiring liver transplant occur in only 1.5-2.7% of cases 9
• Most patients survive without lasting medical sequelae, even when NAC is administered beyond the 8-hour window 9
• Among high-risk patients treated within 10 hours, hepatotoxicity develops in only 4.2% 5