What are the treatment options for Koffex (acetaminophen) overdose?

Treatment of Acetaminophen (Koffex) Overdose

N-acetylcysteine (NAC) is the definitive treatment for acetaminophen overdose and should be administered promptly to all patients with suspected acetaminophen toxicity to prevent liver damage and reduce mortality. 1

Initial Management

• For patients presenting within 4 hours of ingestion, administer activated charcoal prior to starting NAC to reduce drug absorption 1
• Contact a liver transplant center early in the evaluation process for patients with signs of acute liver failure 1
• Obtain acetaminophen levels in all patients presenting with acute liver failure, even when history is lacking, as very high aminotransferases (>3,500 IU/L) strongly correlate with acetaminophen poisoning 1
• Seek immediate medical help or contact a poison control center (1-800-222-1222) in case of overdose 2

Indications for NAC Treatment

• Patients with acetaminophen levels above the treatment line on the Rumack-Matthew nomogram 1, 3
• Patients with known or suspected acetaminophen ingestion with rising aminotransferases indicating evolving liver injury 1
• Patients with acute liver failure where acetaminophen ingestion is possible or circumstances surrounding admission are unclear 1
• Patients with hepatotoxicity due to acetaminophen, including cases of repeated supratherapeutic ingestions 1

NAC Administration Routes

Oral Administration

• Loading dose: 140 mg/kg diluted to 5% solution 1
• Maintenance dose: 70 mg/kg every 4 hours for 17 doses 1
• Side effects: occasional nausea, vomiting, rare urticaria or bronchospasm 1

Intravenous Administration (when oral route is contraindicated)

• Loading dose: 150 mg/kg in 5% dextrose over 15 minutes 1
• First maintenance dose: 50 mg/kg over 4 hours 1
• Second maintenance dose: 100 mg/kg over 16 hours 1
• Consider IV route in patients with gastrointestinal bleeding, worsening mental status, or other contraindications to oral administration 1

Special Considerations

• NAC is most effective when given early but may still provide benefit when administered 48 hours or more after ingestion 1
• For patients with unknown time of ingestion or unreliable history, consider NAC treatment if acetaminophen is detectable in serum or transaminases are elevated 1
• For extended-release formulations or repeated supratherapeutic ingestions, standard nomograms may not apply; consider NAC treatment based on clinical judgment 1, 4
• NAC has been shown to reduce mortality, cerebral edema, and need for inotropic support in patients with acetaminophen-induced hepatic failure 1

Monitoring and Supportive Care

• Monitor patients frequently, preferably in an ICU setting for those with acute liver failure 1
• Allergic reactions to NAC may be treated with discontinuation, antihistamines, and epinephrine for bronchospasm 1
• Supportive care remains crucial, with focus on maintaining airway, ventilation, and circulation while the drug is eliminated 5

Risk Factors for Increased Toxicity

• Chronic alcohol consumption increases risk of hepatotoxicity, even with lower acetaminophen doses 3
• Pre-existing liver disease may increase susceptibility to acetaminophen toxicity 3
• Fasting states may alter acetaminophen metabolism, increasing toxicity risk 1

Prognosis

• Early NAC administration significantly improves outcomes 1
• Without NAC treatment, patients with acetaminophen-induced hepatic failure have higher mortality rates (80% vs 52% with NAC) 1
• NAC treatment reduces progression to coma and need for dialysis in patients with hepatic failure 1

Remember that acetaminophen overdose is the leading cause of acute liver failure in Western countries, but with prompt recognition and appropriate NAC treatment, most patients survive with complete recovery 4.