The U.S. Food and Drug Administration (FDA) has approved a supplemental new drug application (sNDA) for Acetadote, an intravenous (IV) formulation of N-acetylcysteine (NAC), manufactured by Cumberland Pharmaceuticals. This approval streamlines the administration of NAC for preventing or lessening liver injury following potentially toxic ingestion of acetaminophen. Acetaminophen overdose is a leading cause of acute liver failure in the United States, with thousands of individuals experiencing accidental or intentional poisoning annually.
Simplified Dosing Regimen
The updated dosing regimen simplifies the administration of NAC by combining the first two bags of the standard regimen into a single, slower infusion. This approach has been implemented in hospitals and has demonstrated the potential to reduce medication errors and non-allergic anaphylactoid reactions (NAARs) without compromising the efficacy of NAC.
Clinical Evidence
A 2022 retrospective cohort study published in Clinical Toxicology compared a 2-day IV NAC regimen (2-bag) with a 3-bag regimen in patients treated for acetaminophen overdose. The study (n = 869) found that the 2-bag method was associated with significantly fewer and shorter delays in treatment. The median delay was 35 minutes (IQR: 15, 70) in the 2-bag group compared to 65 minutes (IQR: 40, 105) in the 3-bag group (P < .01). Delays longer than an hour were also less frequent in the 2-bag cohort (31% vs 51%; P < .01).
Another retrospective cohort study published in Annals of Pharmacotherapy compared 3-bag with 2-bag NAC regimens for acetaminophen toxicity in pediatric patients. The study (n = 243) found that medication errors were significantly decreased with the 2-bag regimen (23% vs 39%). While overall NAARs were not significantly different, cutaneous NAARs were less frequent in the 2-bag group. There were no statistical differences observed in length of stay, ICU admissions, transplant, or death.
Expert Commentary
"This FDA [sNDA] approval is a significant step forward in the treatment of acetaminophen overdose," said Rick Dart, MD, PhD, director at the Rocky Mountain Poison and Drug Center. "By streamlining the administration of NAC, we can improve patient outcomes and reduce the risk of adverse events. This simplified dosing regimen is a valuable tool for health care providers in managing this potentially life-threatening condition."
"We are thrilled to announce the FDA [sNDA] approval of this simplified dosing regimen for [NAC]," said A.J. Kazimi, CEO of Cumberland Pharmaceuticals. "This important milestone underscores our commitment to improving patient care and providing innovative solutions for urgent medical needs. By streamlining the administration process, we aim to enhance patient outcomes and reduce the burden on health care providers."
