Amoxicillin/clavulanic acid/simvastatin interaction
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Drug hypersensitivity and hepatotoxicity, leading to interaction with simvastatin, and subsequent rhabdomyolysis and acute renal failure: case report A 30-year-old woman with a 12-year history of systemic lupus erythematosus (SLE) developed a type IV hypersensitivity reaction to amoxicillin with hepatotoxicity, leading to a drug interaction with simvastatin, and subsequent rhabdomyolysis and acute renal failure. The woman commenced oral amoxicillin/clavulanic acid containing 875mg and 125mg twice daily, respectively, for dental pain. She developed malaise, chills, muscle pain and a skin eruption after taking her second tablet [time to reaction onset not stated]. She presented 3 days later with odynophagia, a progressive maculopapular rash, diarrhoea and a cough. Her medications also included prednisone and azathioprine for SLE, simvastatin 20 mg/day [therapeutic indication and duration of treatment not stated], captopril, furosemide and folic acid. On examination, she had bilateral conjunctival haemorrhage, a fever, hypotension, and a purpuric rash. Laboratory results revealed increased levels of serum creatinine, CRP, AST, ALT and creatine phosphokinase. Hypoalbuminaemia, and low lymphocyte and platelet counts were observed. Protein and blood were detected in her urine. Arterial blood gas analysis revealed partial pressures of 118mm Hg and 21.2mm Hg for oxygen and carbon dioxide, respectively, and her bicarbonate level was decreased. Diffuse bilateral pulmonary interstitial infiltrates were detected on a chest Xray. Her presumed diagnoses included sepsis, drug hypersensitivity to an antibacterial, an SLE flare, and acute renal failure secondary to rhabdomyolysis. The woman commenced imipenem, paracetamol [acetaminophen], bicarbonate, methylprednisolone followed by prednisone, and clemastine. Over 13 days, prednisone was tapered, and she received hydroxyzine, albumin and furosemide. Her skin lesions were treated topically. She was afebrile by day 3, and her skin lesions improved. On hospital day 8, imipenem was stopped. Laboratory parameters subsequently normalised, and a chest X-ray revealed clearing of her infiltrates. Her antidsDNA antibody level was elevated, and proteinuria persisted. A renal biopsy showed diffuse proliferative glomerulonephritis with segmental sclerosis. Type IV hypersensitivity to amoxicillin was confirmed by intradermal skin tests. On hospital day 28, she was discharged on prednisolone, furosemide, azathioprine, and enalapril. Azathioprine was later changed to mycophenolate mofetil, which was stopped 1 year later. At last follow-up, she had mild chronic renal impairment, and her SLE disease activity was low. Author comment: "In conclusion, the most likely causal pathway for the most severe manifestations was a type IV hypersensitivity reaction due to amoxicillin causing hepatotoxicity leading to increased simvastatin precipitating rhabdomyolysis and acute renal failure." Couto M, et al. Rash, fever and proteinuria after amoxicillin in a SLE patient. Acta 803005533 Reumatologica Portu
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