What is the dosing regimen for oral acetylcysteine (N-acetylcysteine) in acetaminophen (paracetamol) overdose?

Oral Acetylcysteine Dosing for Acetaminophen Overdose

The standard oral N-acetylcysteine (NAC) regimen consists of a loading dose of 140 mg/kg, followed by 70 mg/kg every 4 hours for 17 additional doses (total of 18 doses over 72 hours). 1, 2

Standard Oral Dosing Protocol

Loading Dose:

• 140 mg/kg orally as the initial dose 1, 2
• Dilute the 20% NAC solution to a final concentration of 5% using diet cola or other diet soft drinks 2
• If administered via gastric or Miller-Abbott tube, water may be used as the diluent 2
• Dilutions should be freshly prepared and used within one hour 2

Maintenance Doses:

• 70 mg/kg orally every 4 hours for 17 additional doses 1, 2
• First maintenance dose given 4 hours after the loading dose 2
• Total treatment duration: 72 hours (18 total doses) 1, 3

Critical Timing Considerations

Initiate NAC immediately when acetaminophen overdose is known or suspected, regardless of whether laboratory confirmation is available—do not delay treatment waiting for acetaminophen levels. 1, 2, 4

Efficacy by treatment initiation time:

• 0-8 hours post-ingestion: Maximum protection with only 2.9% developing severe hepatotoxicity 1
• 8-10 hours: Efficacy remains high with 6.1% developing hepatotoxicity 1, 3
• 10-24 hours: Efficacy decreases significantly with 26.4% developing hepatotoxicity 1, 3
• 16-24 hours: Among high-risk patients, 41% develop hepatotoxicity—still better than untreated controls (58%) 1, 3
• Beyond 24 hours: NAC should still be administered as it provides benefit even with delayed treatment 1, 5

Special Dosing Scenarios

If vomiting occurs:

• Repeat the dose if vomited within 1 hour of administration 2
• For persistent vomiting, consider administration via duodenal intubation 2
• Dilution to 5% concentration minimizes vomiting propensity 2

Extended or shortened courses:

• The 72-hour oral regimen is as effective as the 20-hour IV regimen and may be superior when treatment is delayed 3
• NAC can be discontinued when acetaminophen level is undetectable AND liver function tests remain normal 6
• Certain scenarios mandate longer courses: delayed presentation (>24 hours), extended-release formulations, repeated supratherapeutic ingestions, unknown ingestion time, chronic alcohol use, or any elevation in AST/ALT 6, 5

Activated Charcoal Considerations

Administer activated charcoal (1 g/kg) just prior to starting NAC if the patient presents within 4 hours of ingestion. 1, 6

• If activated charcoal has already been given, perform gastric lavage before administering NAC 2, 4
• Activated charcoal adsorbs NAC in vitro and may reduce its effectiveness, but do not delay NAC administration even if charcoal has been given 5, 2

High-Risk Populations Requiring Lower Treatment Threshold

Chronic alcoholics should receive NAC even with acetaminophen levels in the "non-toxic" range, as severe hepatotoxicity can occur with doses as low as 4-5 g/day. 1, 6

Fasting patients are at increased risk and may warrant NAC at lower acetaminophen levels. 1

Malnourished cirrhotic patients or those actively drinking alcohol are at higher risk even at therapeutic doses. 1

Monitoring Requirements

Baseline laboratory studies before NAC initiation:

• Acetaminophen level (drawn 4-24 hours post-ingestion for nomogram use) 2
• AST, ALT, bilirubin, prothrombin time 2
• Creatinine, BUN, blood sugar, electrolytes 2

Ongoing monitoring:

• Repeat AST, ALT, bilirubin, prothrombin time, creatinine, BUN, blood sugar, and electrolytes daily if acetaminophen level is in the potentially toxic range 2
• Monitor hepatic and renal function throughout the detoxification process 4

Critical Pitfalls to Avoid

Never withhold NAC based on low or absent acetaminophen levels if ingestion was remote or occurred over several days—low levels do not rule out acetaminophen poisoning. 6

Do not stop NAC prematurely if any of these red flags develop: any elevation in AST or ALT above normal, rising transaminases, any coagulopathy, detectable acetaminophen level, or clinical signs of hepatotoxicity. 6

For massive overdoses (acetaminophen levels >300-600 μg/mL), standard dosing may be inadequate—consult a poison center or medical toxicologist for potential dose escalation. 6, 7

If encephalopathy due to hepatic failure becomes evident, discontinue NAC to avoid further administration of nitrogenous substances, though this remains a theoretical concern. 2