Acute liver failure after recommended doses of acetaminophen in patients with myopathies (original) (raw)
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Does Therapeutic Use of Acetaminophen Cause Acute Liver Failure?
Pharmacotherapy, 2007
To compare the reported occurrence of liver failure in subjects in prospective trials with that in patients in retrospective reports after repeated use of therapeutic dosages of acetaminophen. Design. Systematic review of the medical literature. Data Source. MEDLINE and EMBASE biomedical and pharmacologic databases. Subjects. Adults who received repeated dosing of acetaminophen 4 g/day or lower for at least 24 hours. Measurements and Main Results. Articles written in several languages were abstracted by trained personnel using a structured abstraction form. Data were categorized by methodology (prospective vs retrospective), acetaminophen dosage, and type of liver effect. A total of 791 articles were identified, which included 30,865 subjects in prospective studies and 9337 patients in retrospective reports. The prospective studies reported no cases of fulminant hepatic injury, liver transplantation, or death due to acetaminophen. Of the 30,865 subjects in these studies, 129 (0.4%) were identified who had a serum aminotransferase level that exceeded the upper limit of normal, including 61 subjects in randomized trials in which the proportion of serum aminotransferase level increase was the same as or less than that in the placebo group and 68 subjects in trials without a placebo group. In addition, 4263 (13.8%) received the maximum recommended therapeutic dosage (3.9-4 g/day). In the retrospective reports, 96 patients (1.0%) had a serum alanine aminotransferase level that exceeded the upper limit of normal, one (0.01%) underwent liver transplantation, and six (0.06%) died. Causality relationship of acetaminophen for each retrospective case was assessed with the Naranjo adverse drug reaction probability scale. The mean ± SD Naranjo score for all 103 retrospective cases was 3.2 ± 1.9, indicating a possible relationship between the increased aminotransferase levels and acetaminophen use. Some retrospective reports contained information suggesting that the patient had ingested an overdose despite a history of therapeutic use. Conclusion. Prospective studies indicated that repeated use of a true therapeutic acetaminophen dosage may slightly increase the level of serum aminotransferase activity, but hepatic failure or death was not reported. Retrospective reports indicated a higher rate of increased serum aminotransferase levels, and several reported associated liver injury and death. The differing results and presence of evidence indicating inaccurate acetaminophen dosage information in some case reports suggests that these cases may be inadvertent overdoses, rather than true therapeutic dosages.
Acetaminophen dose does not predict outcome in acetaminophen-induced acute liver failure
Journal of Investigative …, 2010
Background: Acetaminophen is a dose-dependent toxin. Prognosis in severe acute liver injury is related presumably in part to the dose ingested. We sought to assess the value of acetaminophen dosing information in patients with acute liver failure (ALF) due to acetaminophen toxicity to determine the role of dose as a prognostic indicator.
Clinical Pharmacology & Therapeutics, 2008
Acetaminophen protein adducts (APAP adducts) were quantified in 157 adolescents and children presenting at eight pediatric hospitals with the chief complaint of APAP overdose. Two of the patients required liver transplantation, whereas all the others recovered spontaneously. Peak APAP adducts correlated with peak hepatic transaminase values, time-to-treatment with N-acetylcysteine (NAC), and risk determination per the Rumack-Matthews nomogram. A population pharmacokinetic analysis (NONMEM) was performed with post hoc empiric Bayesian estimates determined for the elimination rate constants (k e ), elimination half-lives (t ½ ), and maximum concentration of adducts (C max ) of the subjects. The mean (±SD) k e and half-life were 0.486 ± 0.084 days −1 and 1.47 ± 0.30 days, respectively, and the C max was 1.2 (±2.92) nmol/ml serum. The model-derived, predicted
Serum Acetaminophen Protein Adduct Concentrations in Pediatric Emergency Department Patients
Journal of pediatric gastroenterology and nutrition, 2016
Acetaminophen toxicity is a common cause of pediatric liver failure. The diagnosis may be limited by the short window of detection of acetaminophen in serum. Recently acetaminophen protein adducts (APAP-CYS) have been used as a biomarker with a longer duration of detection. The objective of this study was to describe the serum concentrations of APAP-CYS in pediatric patients with and without reported therapeutic acetaminophen exposure. A cross sectional study of children age 1 to <12 years presenting to a pediatric emergency department. Subjects were stratified by recent acetaminophen use and had serum APAP-CYS measured using LC/MS. 100 patients were enrolled. All patients whose caregivers denied acetaminophen exposure had non-detectable APAP-CYS. 52% of subjects who were reported to have taken acetaminophen in the preceding 2 weeks had detectable serum APAP-CYS. The APAP-CYS concentrations were positively correlated with higher overall dose and more recent ingestion. APAP-CYS is...
Acetaminophen: Dose-Dependent Drug Hepatotoxicity and Acute Liver Failure in Patients
Digestive Diseases, 2015
Background: Drug-induced liver injury is a rare but serious clinical problem. A number of drugs can cause severe liver injury and acute liver failure at therapeutic doses in a very limited number of patients (<1:10,000). This idiosyncratic drug-induced liver injury, which is currently not predictable in preclinical safety studies, appears to depend on individual susceptibility and the inability to adapt to the cellular stress caused by a particular drug. In striking contrast to idiosyncratic drug-induced liver injury, drugs with dose-dependent hepatotoxicity are mostly detected during preclinical studies and do not reach the market. One notable exception is acetaminophen (APAP, paracetamol), which is a safe drug at therapeutic doses but can cause severe liver injury and acute liver failure after intentional and unintentional overdoses. Key Messages: APAP overdose is responsible for more acute liver failure cases in the USA or UK than all other etiologies combined. Since APAP over...
Liver Enzymes After Acetaminophen Error in Critically Ill Children: A Cohort Study
2021
ObjectivesDrug-associated harm is common but difficult to detect in the hospital setting. In critically ill children, we sought to evaluate drug-associated hepatic injury following enteral acetaminophen error; defined as acetaminophen dosing that exceeds daily maximum recommendations.DesignRetrospective cohort study.SettingTwo pediatric intensive care units within a pediatric hospital center.PatientsChildren (<18 years of age) admitted to the pediatric and cardiac intensive care unit between January 2008 and January 2018, and receiving enteral acetaminophen. We defined acetaminophen dosing error as exceeding daily acetaminophen dosing by > 10% the upper limit of maximum recommended dose for weight and age (>82.5mg/kg/day or > 4400mg/day).Main ResultsWe included 14,146 admissions, who received 147,485 doses of acetaminophen. Acetaminophen dosing errors occurred 1 in every 9.5 patient-days on acetaminophen. ALT and AST decreased significantly over the course of ICU admissi...
Journal of Nepal Paediatric Society, 2021
Introduction: Acetaminophen (APAP) is the most widely used over-the-counter antipyretic and analgesic medicine in children. Although hepatic failure and death is rare in paediatric population, it is one of the most important and dangerous presentation of acetaminophen induced toxicity in children. There is very sparse data regarding APAP induced paediatric acute liver failure in our settings, hence this study was done to know the clinical and demographic profiles as well as outcome of children with APAP induced acute liver failure. Methods: This was a retrospective study done in children aged 0 18 years admitted with the diagnosis of acetaminophen induced acute liver failure in a tertiary paediatric intensive care unit of South India from January 2014 to December 2018. The clinical, demographic profiles and outcome of these patients were reviewed and analysed. Results: A total of 26 children had acetaminophen induced acute liver failure. Out of 26 patients, 53.8% were males and 46.1...
Journal of medical toxicology : official journal of the American College of Medical Toxicology, 2015
Acetaminophen-cysteine adducts (APAP-CYS) are a serum biomarker of acetaminophen exposure, formed when the oxidative metabolite of acetaminophen binds to cysteine residues of hepatic proteins. APAP-CYS adducts become elevated in cases of acute liver failure following acetaminophen overdose and have been proposed as a diagnostic tool to identify acetaminophen-induced acute liver failure when standard testing is inconclusive. A 26-year-old female with history of unexplained, severe hepatitis presented with a second episode of severe hepatitis including coagulopathy and transaminase levels >10,000 U/L. The patient reported ingesting "only a couple" of acetaminophen tablets several days prior to her presentation. An acetaminophen concentration of 14 mcg/mL at presentation aroused suspicion that acetaminophen might have caused the patient's liver failure, despite her adamant denial of overdose. APAP-CYS adduct levels measured from serum obtained 4 days after her presenta...