• Stefan Weiler, Romuald Bellmann, and Gerd A Kullak-Ublick.
• 1 Klinik für Klinische Pharmakologie und Toxikologie und Regionales Pharmacovigilance Zentrum, Universitätsspital Zürich und Universität Zürich.
• Ther Umsch. 2015 Dec 1; 72 (11-12): 737-41.

AbstractRare 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.

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