Thalidomide
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Liver injury in an elderly patient: case report A 76-year-old woman developed severe liver injury during treatment with thalidomide for multiple myeloma. The woman, whose medical history included hypertension and right lower extremity deep vein thrombosis, began receiving thalidomide 200 mg/day and intermittent dexamethasone in addition to her usual warfarin and other medications. Four weeks later, laboratory examinations revealed elevated transaminase levels: AST 179 U/L (normal range 5–34) and ALT 218 U/L (8–35). She was clinically asymptomatic. One week later, she noticed she was jaundiced, and had tea-coloured urine. She began to have mild nausea, fatigue, generalised abdominal discomfort, and a decreased appetite. She presented to a local hospital, and laboratory investigations revealed an AST level of 2376 U/L, an ALT level of 2205 U/L, and a total bilirubin concentration of 5.59 mg/dL. Her albumin level was chronically low, but stable, at 2.0 g/dL (normal range 3.4–4.8). Her INR was > 15 (target range 2–3). The woman was hospitalised and all drugs were stopped. On transfer to another institution, she had a minimal oxygen requirement. She was notably jaundiced with scleral icterus, and bilateral oedema of her lower extremities. Abdominal and pelvic CT scans conducted immediately after her transfer showed scattered hepatic cysts and diffuse fatty infiltration of her liver parenchyma. Her liver function test results began to improve immediately after thalidomide was stopped. She received fresh-frozen plasma and subcutaneous vitamin K, as her warfarin had been held. Overnight, her INR corrected to 2.8 and, over the remainder of her hospitalisation, it gradually improved without additional treatment. A transjugular liver biopsy revealed findings consistent with acute drug-induced injury and underlying nonalcoholic steatohepatitis. Thalidomide was stopped completely and, over her 7-day stay, her liver function tests improved. At discharge her INR had normalised; her ALT level was 165 U/L, her AST level was 86 U/L, and her total bilirubin level was 5.5 mg/dL. On followup at 3 months, her ALT, AST levels and bilirubin levels had normalised [patient outcome not clearly stated]. Author comment: "Evaluation of this case with the Naranjo adverse drug reaction probability scale yielded a score of 7, indicating a probable association between thalidomide and the hepatic injury." Hanje AJ, et al. Thalidomide-induced severe hepatotoxicity. Pharmacotherapy 26: 801043836 1018-1022, No. 7, Jul 2006 - USA
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Reactions 2 Sep 2006 No. 1117
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