Acetaminophen Use Concomitant with Long-Lasting Flucloxacillin Therapy: A Dangerous Combination

Acetaminophen and flucloxacillin both interfere with the γ-glutamyl cycle. Long-lasting concomitant use of flucloxacillin and acetaminophen can lead to 5-oxoproline accumulation and severe high anion gap metabolic acidosis. Females and patients with sepsis, impaired kidney and/or liver function, malnutrition, advanced age, congenital 5-oxoprolinase deficiency and supratherapeutic acetaminophen and flucloxacillin dosage are associated with increased risk. Therefore, a critical attitude towards the prescription of acetaminophen concomitant with flucloxacillin in these patients is needed. We present the case of a 79-year-old woman with severe 5-oxoprolinaemia after long-lasting treatment with flucloxacillin and acetaminophen, explaining the toxicological mechanism and risk factors, and we make recommendations for acetaminophen use in patients with long-lasting flucloxacillin treatment. LEARNING POINTS: Although rare, long-lasting treatment with flucloxacillin concomitant with acetaminophen can lead to severe high anion gap metabolic acidosis. When prescribing long-lasting flucloxacillin therapy in combination with acetaminophen, regular blood gas analysis is needed to evaluate pH and the anion gap. In cases of 5-oxoproline-induced high anion gap metabolic acidosis in patients with long-lasting acetaminophen and flucloxacillin therapy, acetaminophen prescription should be stopped immediately. Replacing flucloxacillin with another antibiotic agent should be considered.