Is dose modification or discontinuation of nilotinib necessary in nilotinib-induced hyperbilirubinemia? |
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Authors: | You-Wen Tan |
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Affiliation: | You-Wen Tan, Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China |
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Abstract: | Nilotinib is a specific breakpoint cluster region-Abelson leukemia virus-tyrosine kinase inhibitor that is used as an effective first- or second-line treatment in imatinib-resistant chronic myelogenous leukemia (CML) patients. Hepatotoxicity due to nilotinib is a commonly reported side effect; however, abnormal liver function test (LFT) results have been reported in asymptomatic cases. When alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are more than five-fold the upper limit of the normal (ULN) or when the serum total bilirubin level is more than three-fold the ULN, dose modification or discontinuation of nilotinib is recommended, resulting in decreased levels of hematological indicators in certain patients with CML. Nilotinib-induced hyperbilirubinemia typically manifests as indirect bilirubinemia without elevated ALT or AST levels. Such abnormal liver functioning is thus not attributed to the presence of a true histologic lesion of the liver. The underlying mechanism may be related to the inhibition of uridine diphosphate glucuronosyltransferase activity. Therefore, nilotinib dose adjustment is not recommended for this type of hyperbilirubinemia, and in the absence of elevated liver enzyme levels or presence of abnormal LFT findings, physicians should consider maintaining nilotinib dose intensity without modifications. |
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Keywords: | Tyrosine kinase inhibitors Nilotinib Chronic myelogenous leukemia Hyperbilirubinemia Drug induced liver injure Liver injury |
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