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Drug points: Acute renal failure due to rhabdomyolysis in presence of concurrent ciprofibrate and ibuprofen treatment

BMJ 1997; 314 doi: https://doi.org/10.1136/bmj.314.7094.1593a (Published 31 May 1997) Cite this as: BMJ 1997;314:1593
  1. S Ramachandrana,
  2. P D Gilesa
  1. a Manor Hospital, Walsall WS2 9PS, A Hartland, University Hospital, Birmingham

    We report a case of acute renal failure due to rhabdomyolysis which occurred while the patient was taking ciprofibrate and ibuprofen.

    A 29 year old Asian man with type M hyperlipidaemia attended the lipid clinic with characteristic xanthomata. Initial cholesterol and triglyceride concentrations were 14.8 mmol/l and 6.86 mmol/l, respectively. In addition to a lipid lowering diet, he received ciprofibrate 100 mg daily, which resulted in his cholesterol concentration dropping to 8.2 mmol/l and his triglyceride concentration to 3.3 mmol/l. Further improvement followed when the dose was increased to 200 mg daily, cholesterol and triglyceride concentrations falling to 6.6 mmol/l and 1.9 mmol/l, respectively.

    After six months of treatment and three weeks after tests showing normal liver function and creatine kinase activity he developed a painful heel. He obtained ibuprofen 200 mg over the counter, and the dose was increased to 400 mg by his general practitioner. The pain became generalised, his urine turned “muddy,” and he presented as an emergency complaining of a “stiff body.” Urea concentration was 6.9 mmol/l. Intravenous urography was performed because renal colic was suspected. Two days later he developed renal failure, which required transfer to a renal unit (urea concentration 23 mmol/l, creatinine concentration 647 μmol/l, potassium concentration 6.2 mmol/l). Creatine kinase activity was 13 740 U/l. Subsequently, he recovered fully.

    In the month that this patient developed renal failure (April 1995) the data sheet for Modalim (ciprofibrate) was amended, reducing the maximum recommended dose to 100 mg daily because of the high incidence of rhabdomyolysis reported in France with 200 mg.

    Ibuprofen and ciprofibrate are heavily bound by protein (Sanofi Winthrop, technical brochure for ciprofibrate, 1992)1 2 and contain propionic acid groups.2 We postulate that ibuprofen displaced ciprofibrate, making what had been a safe dose for our patient become toxic, causing rhabdomyolysis and renal failure. This situation was probably exacerbated by radiological contrast medium. This case is important because ibuprofen can be bought without a prescription and can affect the pharmacokinetics of concurrent drug treatment.

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