UMEM Educational Pearls


NAC is an effective antidote against acetaminophen (APAP) toxicity in preventing acute hepatotoxicity. It provides cysteine that is essential for glutathione synthesis and its availability is rate limiting.

Currently, PO and IV formulation is available in the U.S. Regardless of the route, NAC is equally effective in preventing APAP induced acute hepatotoxicity when administered within 8 hours after single acute ingestion. 1

Adverse effects of NAC

1.     Anaphylactoid reaction

a.     More frequently reported with IV administration and during the first regimen of NAC (150 mg/kg over 60 min) administration. (dose and rate dependent)

b.     Higher risk of anaphylactoid reaction in patients with negative APAP vs. patients with elevated APAP level.2

c.      Management: Benadryl as needed and slow infusion rate.

2.     Hyponatremia in children if inappropriate volume of diluent (D5W) used. Dose calculator:

3.     Laboratory: increase Prothrombin time (PT).3

4.     Fatality from iatrogenic NAC overdose has been reported.


Advantage of IV NAC

1.     Convenience

2.     100% bioavailability

3.     Shorter hospital length of stay

4.     Minimum GI symptoms (nausea & vomiting) compared to PO route


Indication of IV NAC

1.     Severe hepatotoxicity or fulminant liver failure

2.     APAP poisoning during pregnancy

3.     Unable to tolerate PO intake (nausea, vomiting, altered mental status)

However many clinicians administer IV NAC for their advantages over PO NAC.


 Take home message:

1.     PO and IV NAC are equally effective when administered within 8 hours after single acute ingestion.

2.     Anaphylactoid reaction is frequently encountered AE during the infusion of 1st NAC regimen and patients with negative/low APAP level may be at higher risk.

3.     No emergent need to start NAC in presumed acetaminophen overdose patients prior to obtaining APAP level.


  1. Prescott L. Oral or intravenous N-Acetylcysteine for acetaminophen poisoning? Ann Emerg Med 2005;45:409-413.
  2. Schmidt LE. Identification of patients at risk of anaphylactoid reactions to N-acetylcysteine in the treatment of paracetamol overdose. Clin Toxicol 2013;51:467-472.
  3. Jang DH et al. In vitro study of N-acetylcysteine on coagulation factors in plasma samples from healthy subjects. J med Toxicol 2012;9:49-53.