A dosing regimen for immediate N-acetylcysteine treatment for acute paracetamol overdose

Abstract

Context. Current treatment of paracetamol (acetaminophen) poisoning involves initiating a 3-phase N-acetylcysteine (NAC) infusion after comparing a plasma concentration, taken ≥4 h post-overdose, to a nomogram. This may result in dosing errors, a delay in treatment, or possibly more adverse effects – due to the use of a high dose rate for the first infusion when treatment is initiated. Objective. Our aim was to investigate a novel dosing regimen for the immediate administration of NAC on admission at a lower infusion rate. Methods. We used a published population pharmacokinetic model of NAC to simulate a scenario where a patient presents to the hospital 2 h post-overdose. The conventional regimen is commenced 6 h post-overdose when the 4-h plasma paracetamol concentration is available. We investigated an NAC infusion using a lower dosing rate initiated immediately on presentation. We determined a dosing rate that gave an area under the curve (AUC) of the concentration-time curve that was the same or greater than that from the conventional regimen on 90% of occasions. Results. Lower dosing rates of NAC initiated immediately resulted in a similar exposure to NAC. An infusion of 110 mg/kg over the first 5 h (22 mg/kg/h) followed by the last two phases of the conventional regimen, or 200 mg/kg over 9 h (22.6 mg/kg/h) followed by the last phase of the conventional regimen could be used. Conclusion. The novel dosing regimen allowed immediate treatment of a patient using a lower dosing rate. This greatly simplifies the current dosing regimen and may reduce NAC adverse effects while ensuring the same amount of NAC is delivered.

Keywords:

• Liver
• Paracetamol
• N-acetylcysteine