Metabolic acidosis caused by concomitant use of paracetamol (acetaminophen) and flucloxacillin? A case report and a retrospective study

• Published in: European journal of clinical pharmacology 2017-11, Vol.73 (11), p.1459-1465
• Main Authors: Berbee, J. K., Lammers, L. A., Krediet, C. T. P., Fischer, J. C., Kemper, E. M.
• Format: Article
• Language: English
• Subjects: Acetaminophen; Acetaminophen - adverse effects; Acidosis; Acidosis - chemically induced; Aged; Analgesics; Analgesics, Non-Narcotic - adverse effects; Anti-Bacterial Agents - adverse effects; Antibiotics; Biomedical and Life Sciences; Biomedicine; Case reports; Differential diagnosis; Drug interaction; Drug Interactions; Floxacillin - adverse effects; Flucloxacillin; Humans; Hydrogen ions; Male; Metabolic acidosis; Metabolism; Paracetamol; Patients; Penicillin; pH effects; Pharmacoepidemiology and Prescription; Pharmacology/Toxicology; Poisoning
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-017-2311-6

Purpose A patient was identified with severe metabolic acidosis, a high anion gap and 5-oxoproline accumulation, probably caused by the simultaneous use of paracetamol (acetaminophen) and flucloxacillin. We wanted to investigate the necessity to control the interaction between both drugs with an automatic alert system. Methods To investigate the relevance of the interaction of paracetamol and flucloxacillin, a retrospective study was conducted. Data on paracetamol and flucloxacillin prescriptions and laboratory data (pH, Na + , HCO 3 − , Cl − , albumin and 5-oxoproline levels) were combined to assess the prevalence of acidosis, calculate the anion gap and analyse 5-oxoproline levels in clinically admitted patients using both drugs simultaneously. Results In the 2-year study period, approximately 53,000 admissions took place in our hospital. One thousand and fifty-seven patients used paracetamol and flucloxacillin simultaneously, of which 51 patients (4.8%) had a serum pH ≤ 7.35. One patient, the same patient as presented in the case report, had a high anion gap and a toxic level of 5-oxoproline. Conclusion The prevalence of metabolic acidosis is very low and the only patient identified with the interaction was recognised during normal clinical care. We conclude that automatic alerts based on simultaneous use of paracetamol and flucloxacillin will generate too many signals. To recognise patients earlier and prevent severe outcomes, a warning system (clinical rule) based on paracetamol, flucloxacillin and pH measurement may be helpful. Early calculation of the anion gap can narrow the differential diagnosis of patients with metabolic acidosis and measurement of 5-oxoproline can explain acidosis due the interaction of paracetamol and flucloxacillin.