Indeed, APAP intoxications still represent a major public health concern in the United States and Anglo-Saxon countries ( Budnitz et al., 2011). (2014), after a 16-year evaluation of the effectiveness of pack size restrictions, a very small effect was found. Thus, in 1998, the British authorities in the United kingdom were forced to review the packaging. In particular, between 19, there was a very high number of intoxications with APAP, which caused numerous hospitalizations and deaths.

APAP was first introduced in 1955, and the first case of intoxication was reported in 1966. Timing of treatment, ranging from 8 to 24 h from APAP overdose, regardless of the regimen or route of administration, is important to prevent or minimize liver damage, particularly in children and in elderly and obese patients.ĭrug-induced liver injury (DILI) is a potentially serious hazard of high doses of N-acetyl-para-aminophenol or more simply acetaminophen (APAP), often taken in suicidal attempts, particularly in Anglo-Saxon countries ( Bernal et al., 2010). The most frequent AEs reported were anaphylactic reactions, followed by cutaneous AEs for the IV route and intestinal AEs for the oral one.Ĭonclusion: NAC improves hepatotoxicity and reduces mortality. The timing of initiation of NAC treatment showed different results in terms of occurrence of hepatotoxicity and mortality if started within 8 h and no more than 24 h from APAP overdose, either intravenously or orally, NAC administration was efficacious in terms of mortality. regimen and 72 h for oral administration. Large variability of NAC regimens was found, i.e., intravenous (I.V.) (100–150 mg/kg) and oral (70–140 mg/kg), and length of treatment varied-12, 24, or 48 h for I.V. The mortality rate across different studies ranged from 0 to 52%. Results: In total, 34 studies of NAC usage in APAP-related DILI cases with 19,580 patients were identified, of which 2,376 patients developed hepatotoxicities. The prespecified primary outcomes were DILI-related mortality, hepatotoxicity, and adverse events (AEs). Methods: Bibliographic databases (PubMed, Web of Science, Embase, and MEDLINE) were searched for retrospective and prospective cohort studies, case series, and clinical trials. Our objective was to systematically review evidence of the use of NAC as a therapeutic option for APAP overdose and APAP-related DILI in order to define the optimal treatment schedule and timing to start treatment. 6Servicio de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, SpainĪims: N-Acetylcysteine (NAC) is used as an antidote in acetaminophen (APAP) overdose to prevent and mitigate drug-induced liver injury (DILI).5Centro de Investigación Biomedica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Madrid, Spain.4UCICEC IBIMA, Plataforma SCReN (Spanish Clinical Research Network), Malaga, Spain.3Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain.2Institute of Physiology and Pharmacology, Lithuanian University of Health Sciences, Kaunas, Lithuania.D’Alessandro,” PROMISE, Università degli Studi di Palermo, Palermo, Italy 1Medicina Interna ed Epatologia, Dipartimento di Promozione della Salute, Materno-infantile, di Medicina Interna e Specialistica di Eccellenza “G.Anna Licata 1*, Maria Giovanna Minissale 1, Simona Stankevičiūtė 2, Judith Sanabria-Cabrera 3,4, Maria Isabel Lucena 3,4,5, Raul J Andrade 5,6 and Piero Luigi Almasio 1

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