PHARMA/TOXICOLOGY
Get the Knack for NAC: Optimizing N-acetylcysteine Protocols in Acetaminophen Overdose Management
SAEM PULSE | SEPTEMBER-OCTOBER 2024
By Megan Musselman, PharmD, MS, and Maria Rudis, PharmD, on behalf of the SAEM Toxicology/Addiction Medicine Interest Group and the SAEM Academic Emergency Medicine Pharmacists Interest Group
64
Patients with acetaminophen overdose frequently present to the emergency department. According to the 2022 National Poison Data System annual report, acetaminophen remains the second most common substance linked to fatalities. Acetaminophen poisoning occurs when the liver's ability to detoxify acetaminophen is overwhelmed, leading to the accumulation of the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). Normally, NAPQI is detoxified by glutathione. In cases of overdose, glutathione stores are depleted, causing hepatocellular damage and potential liver failure. N-acetylcysteine (NAC) is a highly effective antidote; when administered
within the first eight hours, it prevents most liver injuries and reduces mortality. For decades, dosing IV NAC has followed a "one size fits all" approach. The FDA-approved IV NAC regimen involves administering 300 mg/kg over 21 hours using three separate IV infusion bags, each with its own concentration and infusion rate. However, recent efforts have aimed at more individualized dosing regimens. These include optimizing the delivery of the standard 21-hour protocol, increasing the dose and duration of NAC in massive (“high risk”) ingestions, and shortening NAC administration when liver function tests return to baseline.
Optimization of the Standard 21-hour NAC IV Regimen
The traditional 21-hour NAC IV regimen, administered in three sequential doses with differing doses and concentrations, can lead to interruptions in antidote infusion and is associated with dosing errors. Additionally, non-allergic anaphylactoid reactions (NAAR) frequently occur due to the large initial NAC dose (150 mg/kg) in the first bag. A simplified two-dose regimen is appealing as it may reduce interruptions in care, medication errors, and the incidence of dose-related NAARs. Two-dose regimens generally extend the initial bolus over several hours. Since NAARs are typically dose-related, reducing the infusion rate from the