Flucloxacillin/paracetamol interaction
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Metabolic acidosis in elderly patients: 2 case reports Two elderly women [ages not clearly stated] with sepsis following hemiarthroplasty for femoral neck fracture developed metabolic acidosis during concomitant administration of flucloxacillin and paracetamol [acetaminophen]. A woman in her early 80s began receiving IV flucloxacillin 2g four times daily 18 days after hemiarthroplasty; she was also receiving regular paracetamol [route and dosage not stated]. On postoperative day 51, laboratory investigations included the following: albumin 22 g/L, sodium 148.7 mmol/L, potassium 2.86 mmol/L, chlorine 113.8 mmol/L, urea 8.6 mmol/L, creatinine 145 µmol/L and CRP 72 mg/L. Arterial blood gas analysis revealed metabolic acidosis with a corrected anion gap of 28 mEq/L and base excess of -15.2 mmol/L. She began receiving sodium bicarbonate and potassium. A provisional diagnosis of pyroglutamic acidosis was confirmed by urine testing, which revealed a gross increase in pyroglutamate excretion. Flucloxacillin and paracetamol were discontinued. Urine and blood cultures grew Enterococcus faecalis, and daptomycin was initiated. Over the next 5 days, her acidosis improved. Despite removal of the hip prosthesis due to unresolved sepsis, her renal function worsened and she died 3 weeks later. A woman in her late 80s began receiving oral flucloxacillin 500mg four times daily 6 days after hemiarthroplasty. Due to worsening sepsis, she was switched to IV flucloxacillin 1g four times daily, with regular paracetamol 1g four times daily [route not stated]. On postoperative day 30, she developed new-onset atrial fibrillation, thought to be secondary to hypokalaemia. Her albumin, potassium and CRP levels were 22 g/L, 2.34 mmol/L and 207 mg/L, respectively. Arterial blood gas analysis revealed metabolic acidosis with a corrected anion gap of 21 mEq/L and base excess of -14.3 mmol/L. She was diagnosed with pyroglutamic acidosis, and flucloxacillin and paracetamol were discontinued. Her corrected anion gap improved following treatment with bicarbonate. An excision arthroplasty was performed on day 43, but she died 5 days later. Postmortem urine testing revealed increased pyroglutamate excretion. Author comment: "[A] score of 7 on the Naranjo scale suggests that the effects were probably due to use of this drug combination." Amer H, et al. Refractory metabolic acidosis in patients with sepsis following hemiarthroplasty for femoral neck fracture: A causative role for paracetamol and flucloxacillin?. BMJ Case Reports : Jan 2011. Available from: URL: http:// 803061307 dx.doi.org/10.1136/bcr.05.2011.4292 - United Kingdom
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Reactions 15 Oct 2011 No. 1373
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