title: [5-0xoproline (pyroglutamic acid) acidosis and acetaminophen- a differential diagnosis in high anion gap metabolic acidosis].
abstract: Rare cases of high anion gap metabolic acidosis during long-term paracetamol administration in therapeutic doses with causative 5-oxoproline (pyroglutamic acid} accumulation have been reported. Other concomitant risk factors such as malnutrition, alcohol abuse, renal or hepatic dysfunction, comedication with flue/oxacillin, vigabatrin, netilmicin or sepsis have been described. The etiology seems to be a drug-induced reversible inhibition of glutathione synthetase or 5-oxoprolinase leading to elevated serum and urine levels of 5-oxoproline. Other more frequent differential diagnoses, such as intoxications, ketoacidosis or lactic acidosis should be excluded. Causative substances should be stopped. 5-oxoproline concentrations in urine can be quantified to establish the diagnosis. Adverse drug reactions, which are not listed or insufficiently described in the respective Swiss product information, should be reported to the regional pharmacovigilance centres for early signal detection. 5-0 xoproline acidosis will be integrated as a potential adverse drug reaction in the Swiss product information for paracetamol.
authors.affiliation: 1 Klinik für Klinische Pharmakologie und Toxikologie und Regionales Pharmacovigilance Zentrum, Universitätsspital Zürich und Universität Zürich.
authors.forename: Stefan
authors.initials: S
authors.lastname: Weiler
authors.affiliation: 2 Arbeitsgruppe für Klinische Pharmakokinetik, Gemeinsame Einrichtung für Internistische Notfall- und Intensivmedizin, Universitätsklinik für Innere Medizin I, Medizinische Universität Innsbruck.
authors.forename: Romuald
authors.initials: R
authors.lastname: Bellmann
authors.affiliation: 1 Klinik für Klinische Pharmakologie und Toxikologie und Regionales Pharmacovigilance Zentrum, Universitätsspital Zürich und Universität Zürich.
authors.forename: Gerd A
authors.initials: GA
authors.lastname: Kullak-Ublick
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000138:Acidosis / Q000139:chemically induced* / Q000175:diagnosis* / Q000652:urine; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects; D015415:Biomarkers / Q000652:urine; D003937:Diagnosis, Differential; D006801:Humans; D008508:Medication Errors / Q000517:prevention & control*; D011761:Pyrrolidonecarboxylic Acid / Q000652:urine*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D018712:Analgesics, Non-Narcotic; D015415:Biomarkers; D000082:Acetaminophen; D011761:Pyrrolidonecarboxylic Acid