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Drug-induced hepatotoxicity in the form of acute hepatocellular injury: case report A 41-years old woman developed drug-induced hepatotoxicity in the form of acute hepatocellular injury following amoxicillin/ clavulanic acid misuse during treatment with tolvaptan for autosomal dominant polycystic kidney disease (ADPKD). The woman had a history of hypertension and ADPKD was eligibile for treatment with tolvaptan. She started receiving treatment with split-dose regimen of tolvaptan 60mg [Jinarc; route not stated], 45mg and 15mg per day. After 28 days, at week 4, the initial dose was titrated upwards to a split-dose regimen of tolvaptan 90mg i.e 60mg+30mg per day. After 28 days, at week 8, the dose was uptitrated to a target split-dose regimen of tolvaptan 120mg i.e 90mg+30mg per day. On week 12, blood testing revealed slightly increased AST and ALT levels; however, all other parameters were normal and therefore treatment with the target dose tolvaptan 120mg was continued. After 16 weeks of treatment, laboratory investigations revealed a further increase of liver enzymes levels of AST 172 U/L and ALT 378 U/L. No alterations in the other laboratory values were observed and bilirubin total level was 0.25 mg/dL, alkaline phosphatase 32 U/L, albumin 4.3 g/dL, γ-glutamyltransferase 18 UI/mL, pseudocholinesterase 8041 UI/mL, creatinine 1.8 mg/dL vs 1.42 mg/dL before starting tolvaptan. An abdominal ultrasonography revealed multiple liver cysts. Further investigations also revealed that, she had taken amoxicillin/clavulanic acid 825/175mg twice a day [route not stated] for 1 week, without medical prescription for fever and pharyngitis about 5 weeks prior to the start of transaminase increase (the antibiotic was taken at week 11). Diagnosis of drug-induced hepatotoxicity in the form of acute hepatocellular injury secondary to tolvaptan and amoxicillin/clavulanic acid was made. The woman’s treatment with tolvaptan was discontinued at 16 week. Two weeks later, the laboratory report revealed an additional increase of AST 172 U/L and ALT 711 U/L and 1 week later, a further increase of AST 319 U/L and ALT 808 U/L was observed. At week 21, aminotransferase levels began to decrease and returned to normal levels by week 24. The woman started therapy with tolvaptan again on week 24 in doses of 45mg and 15mg. Further monthly blood testings revealed no more elevation of aminotransferases and they remained below the upper limit of the normal range. Pellegrino AM, et al. Idiosyncratic hepatic toxicity in autosomal dominant polycystic kidney disease (ADPKD) patient in combined treatment with tolvaptan and amoxicillin/ 803500513 clavulanic acid: A case report. BMC Nephrology 20: 426, No. 1, 21 Nov 2019. Available from: URL: http://doi.org/10.1186/s12882-019-1612-7

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Reactions 12 Sep 2020 No. 1821