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Drug interactions between tacrolimus and clotrimazole troche: a data mining approach followed by a pharmacokinetic study.

Abstract：

PURPOSE:This study investigated the effects of clotrimazole troche on the risk of transplant rejection and the pharmacokinetics of tacrolimus. METHODS:The data mining approach was used to investigate whether the use of clotrimazole increased the risk of transplant rejection in patients receiving tacrolimus therapy. Patient data were acquired from the US Food and Drug Administration's Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the end of 2017. Next, we retrospectively investigated the effect of clotrimazole troche on tacrolimus pharmacokinetics in seven patients who underwent heart transplantation between March and December 2017. RESULTS:The FAERS subset data indicated a significant association between transplant rejection and tacrolimus with clotrimazole [reporting odds ratio 1.92, 95% two-sided confidence interval (95% CI) 1.43-2.58, information component 0.81, 95% CI 0.40-1.23]. The pharmacokinetic study demonstrated a significant correlation between trough concentration (C0) and area under the concentration-time curve of tacrolimus after discontinuation of clotrimazole (R2 = 0.60, P < 0.05) but not before its discontinuation. Furthermore, the median clearance/bioavailability of tacrolimus after discontinuation of clotrimazole was 2.2-fold greater than that before its discontinuation (0.27 vs. 0.59 L/h/kg, P < 0.05). The median C0 decreased from 10.7 ng/mL on the day after discontinuation of clotrimazole to 6.5 ng/mL at 1 day and 5.3 ng/mL at 2 days after its discontinuation. CONCLUSION:Immediate dose adjustments of tacrolimus may be beneficial to avoid transplant rejection when clotrimazole troche is added or discontinued.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Uno T,Wada K,Hosomi K,Matsuda S,Ikura MM,Takenaka H,Terakawa N,Oita A,Yokoyama S,Kawase A,Takada M

doi

10.1007/s00228-019-02770-6

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

117-125

issue

eissn

0031-6970

issn

1432-1041

pii

10.1007/s00228-019-02770-6

journal_volume

pub_type

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Drug interactions between tacrolimus and clotrimazole troche: a data mining approach followed by a pharmacokinetic study.