Clinically significant drug‐drug interaction between tacrolimus and fluconazole in stable renal transplant recipient and literature review
JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS(2020)
摘要
What is known and objective Clinical use of fluconazole against fungal infections in renal transplant patients is complicated by the potentially marked and unpredictable drug-drug interactions (DDIs). We report a case of tacrolimus-fluconazole DDI in a stable renal transplant recipient and describe the mechanism, magnitude and duration of this DDI through a literature review. Case summary A 38-year-old woman experienced a 9.1-fold increase in dose-normalized tacrolimus trough level (trough concentration/weight-normalized daily dose) and an 87% decrease in weight-normalized daily dose (daily dose/body weight) in the treatment of documented Candida albicans oesophagitis by fluconazole. After discontinuation of fluconazole for 161 day, a 26% reduction in weight-normalized daily dose was required to maintain therapeutic exposure. What is new and conclusion Oral fluconazole has a more significant impact on its drug interactions with tacrolimus than intravenous fluconazole. Gene screening for CYP3A5 6986 A>G and ABCB1 3435 C>T in organ transplant recipients may help in preventing DDI and facilitating tacrolimus dose adjustment.
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关键词
drug-drug interaction,fluconazole,genetic polymorphism,renal transplantation,tacrolimus,therapeutic drug monitoring
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