- OVERDOSE: Overdose with intravenous NAC most commonly causes an anaphylactoid response. Status epilepticus, cerebral edema, anoxic encephalopathy and death have been reported after massive intravenous overdose. ADVERSE EVENTS: N-acetylcysteine (NAC) is used therapeutically primarily as a mucolytic or as an antidote to acetaminophen overdose. COMMON: The primary toxicity of NAC consists of nausea/vomiting, particularly after oral therapy, and anaphylactoid reactions which can occur after intravenous therapy and may be life-threatening. INTRAVENOUS: Mild anaphylactoid reactions to intravenous NAC are fairly common, consisting of rash, flushing, urticaria and less often bronchospasm. These reactions most often occur during the initial infusion, and may be related to the dose and rate of administration. SEVERE: More severe reactions such as hypotension occur less often and are usually associated with an inadvertent overdose of intravenous NAC.
Range of Toxicity:
- TOXICITY: Limited data. Severe toxicity related to NAC administration is usually related to the development of acute allergic reactions following IV administration, which usually responds to supportive care, but in some cases deaths have occurred. PEDIATRIC: A 16 kg 30-month-old child died after developing status epilepticus, respiratory arrest and cerebral edema following 39,207 mg NAC (2,450 mg/kg) IV over 6.5 hours (normal dose 3,325 mg or 208 mg/kg). ADULT: A 21-year-old woman developed intractable seizures, cerebral edema followed by uncal herniation after inadvertently receiving 150 g of IV acetylcysteine over 32 hours; she remained in a persistent vegetative state. In another case, a 20 year-old woman inadvertently received an incorrect dose of N-acetylcysteine (total dose of 38,400 mg (a 10-fold error)) over 14 hours and developed only mild symptoms and laboratory evidence of hemolysis; she recovered completely. THERAPEUTIC DOSE: Acetaminophen Overdose, ORAL LOADING Dose: Adult OR Pediatric: 140 mg/kg orally as a 5% solution in a soft drink or juice. ORAL MAINTENANCE Dose: 70 mg/kg orally as a 5% solution in a soft drink or juice every 4 hrs for 72 hrs maintenance. NO change in dose is necessary in patients who have received activated charcoal. INTRAVENOUS: Adult: 150 mg/kg NAC in 200 mL D5W over 60 minutes, followed by 50 mg/kg 500 mL D5W over next 4 hrs, then 100 mg/kg in 1000 mL D5W over next 16 hrs. Pediatric: The amount of NAC administered is the same on a mg/kg basis, but doses are given in smaller amounts of D5W to avoid hyponatremia for excessive free water administration.
- Decontamination: GI decontamination is usually not necessary because many patients experience vomiting with oral NAC.
- Support: Anaphylactoid symptoms may develop; monitor patient airway. Bronchospasm should be treated aggressively. All patients developing a significant anaphylactoid reaction to NAC should be admitted to an ICU.
- Acute allergic reaction: Symptoms are usually dose-dependent; epinephrine, antihistamines and steroids may be useful. Treatment guidelines: Flushing: No treatment indicated; continue NAC. Urticaria: Diphenhydramine 1 mg/kg and evaluate ongoing need for NAC. Angioedema: Diphenhydramine 1 mg/kg; stop NAC and reevaluate ongoing need for NAC. Respiratory symptoms: Stop NAC; treat symptoms with beta2 agonists, restart NAC if NO symptoms develop for 1 hour.
- Nausea and vomiting: Monitor fluids and electrolytes. Replace fluids as indicated. Patient should be receiving 5% solution of NAC (not 10% or 20%). Metoclopramide: 1 mg/kg IV or IM 30 min before the NAC dose (extrapyramidal symptoms possible).
- Seizure: IV benzodiazepines. Add barbiturates, propofol, or midazolam infusion for persistent seizures.
- Hemodialysis: Based on limited data, IV NAC was removed by hemodialysis; mean hemodialysis clearance of 135 mL/min was reported.