What is the oral dose of acetylcysteine (N-acetylcysteine) for acetaminophen (paracetamol) overdose and as a mucolytic agent?

Oral Acetylcysteine Dosing

For acetaminophen overdose, administer oral N-acetylcysteine (NAC) as a loading dose of 140 mg/kg, followed by 70 mg/kg every 4 hours for 17 additional doses (total 72-hour protocol). 1, 2, 3

Acetaminophen Overdose Protocol

Standard Oral Dosing Regimen

• Loading dose: 140 mg/kg orally or via nasogastric tube, diluted to a 5% solution 1, 2
• Maintenance doses: 70 mg/kg every 4 hours for 17 additional doses (total treatment duration: 72 hours) 1, 2, 3
• Administer activated charcoal (1 g/kg) just prior to starting NAC if the patient presents within 4 hours of ingestion 1, 2

Critical Timing Considerations

• Initiate NAC within 8 hours of ingestion for maximal hepatoprotection—only 2.9% develop severe hepatotoxicity when treated this early 1
• Efficacy decreases with delay: 6.1% develop severe hepatotoxicity when started within 10 hours, versus 26.4% when started 10-24 hours post-ingestion 1, 3
• NAC remains beneficial even when started 16-24 hours after ingestion (41% hepatotoxicity rate versus 58% in untreated historical controls) 1, 3
• Continue treatment even beyond 24 hours if hepatotoxicity is present or acetaminophen levels remain detectable 1

Shortened Treatment Duration (Selected Low-Risk Cases)

While the standard 72-hour protocol is established practice, some evidence suggests shorter courses may be safe in carefully selected patients:

• 24-36 hour protocols may be considered for uncomplicated cases presenting early with normal liver function tests at 12-24 hours and undetectable acetaminophen levels 1, 4
• In one retrospective series, no hepatotoxicity occurred in patients treated <24 hours who had normal labs, though 8-16% developed hepatotoxicity with longer treatment durations (suggesting these were higher-risk patients) 4
• Critical caveat: Shortened protocols are NOT appropriate for delayed presentations (>24 hours), extended-release formulations, repeated supratherapeutic ingestions, massive overdoses, or patients with any evidence of hepatotoxicity 1, 5

Special Clinical Scenarios Requiring Standard or Extended Treatment

Mandatory full 72-hour protocol or longer:

• Delayed presentation (>24 hours post-ingestion) 1, 2
• Extended-release acetaminophen formulations 1, 2
• Repeated supratherapeutic ingestions (>4g per 24 hours over multiple days) 1, 2
• Unknown time of ingestion with detectable acetaminophen levels 1
• Any elevation in AST or ALT above normal 1
• Chronic alcohol use (increased susceptibility to hepatotoxicity) 1, 2
• Patients with established hepatic failure—continue NAC until transaminases decline and INR normalizes 1

Massive overdoses (acetaminophen levels above the "300-line"):

• Consider increased NAC dosing beyond standard protocol, with step-wise increases at the 300-, 450-, and 600-lines on the nomogram 6
• These patients develop hepatotoxicity at higher rates despite standard dosing 6

Discontinuation Criteria

NAC can be stopped when ALL of the following are met:

• Acetaminophen level is undetectable 1
• AST and ALT remain normal (no elevation above baseline) 1
• No coagulopathy present 1
• Patient does not fall into high-risk categories listed above 1

Red flags mandating continuation or restart of NAC:

• Any elevation in AST or ALT 1
• Rising transaminases 1
• Any coagulopathy 1
• Detectable acetaminophen level 1
• Clinical signs of hepatotoxicity 1

Comparison: Oral vs. Intravenous NAC

• The 72-hour oral regimen is as effective as the 20-hour IV regimen and may be superior when treatment is delayed 3
• IV NAC regimen: 150 mg/kg over 15 minutes, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours 1, 2
• Choose IV route if patient cannot tolerate oral administration due to vomiting or altered mental status 7

Mucolytic Use (Non-Overdose Indication)

For mucolytic therapy in respiratory conditions, acetylcysteine dosing differs entirely from overdose protocols and is not addressed in the acetaminophen overdose guidelines provided 8. This represents a separate clinical indication with distinct dosing requirements.

Common Pitfalls

• Do not delay NAC while awaiting confirmatory acetaminophen levels if overdose is strongly suspected 2
• The Rumack-Matthew nomogram does NOT apply to presentations >24 hours, repeated supratherapeutic ingestions, or extended-release formulations—treat based on acetaminophen levels and liver function tests instead 1
• Low or absent acetaminophen levels do not rule out poisoning if ingestion was remote or occurred over several days 1
• Patients may develop hepatotoxicity despite "no risk" nomogram placement due to inaccurate history or increased susceptibility 1