Romanian Society of Pharmaceutical Sciences
 

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EVALUATING THE RELATIONSHIP BETWEEN THE NUMBER OF DRUG INTERACTIONS AND TACROLIMUS EXPOSURE IN THE FIRST YEAR POST-KIDNEY TRANSPLANTATION: A COMPARATIVE STUDY OF INTERACTION DATABASES

NIKOLA STEFANOVIĆ 1*, MAŠA JOVIĆ 2, KATARINA DANKOVIĆ 2, IVANA DAMNJANOVIĆ 1, BRANISLAV APOSTOLOVIĆ 3, BRANKA MITIĆ 3,4, RADMILA VELIČKOVIĆ-RADOVANOVIĆ 3,5

1University of Nis, Faculty of Medicine, Department of Pharmacy, Dr Zorana Djindjica 81 Blvd., 18000 Nis, Serbia
2 University of Nis, Faculty of Medicine, Dr Zorana Djindjica 81 Blvd., 18000 Nis, Serbia
3 University Clinical Center Nis, Clinic of Nephrology, Dr Zorana Djindjica 48 Blvd., 18000 Nis, Serbia
4 University of Nis, Faculty of Medicine, Department of Internal Medicine, Dr Zorana Djindjica 81 Blvd., 18000 Nis, Serbia
5 University of Nis, Faculty of Medicine, Department of Pharmacology with toxicology, Dr Zorana Djindjica 81 Blvd., 18000 Nis, Serbia

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The objective of this study was to identify the most common drug-drug interactions (DDIs) involving tacrolimus (Tac), with a particular focus on potentially serious interactions within the first year post-kidney transplantation, using three different databases. Also, the study aimed to assess the impact of the number of DDIs on Tac dose requirements and exposure, including intra-patient variability (IPV). The observational retrospective study included 99 kidney transplant recipients undergoing Tac-based immunosuppression. The review and classification of Tac DDIs were conducted using the British National Formulary (BNF), Lexicomp®, and Epocrates®. Among the 69 identified DDIs, the most common interactions were those requiring patient monitoring, with the exception of the BNF database. Only 13% of DDIs were common to all three databases. The number of Tac DDIs identified by the BNF was positively associated with Tac trough concentration (C0)-to-dose ratio (C0/D) between 6- and 12- months post-transplantation. Additionally, significantly more patients with two or more identified Tac DDIs, according to the BNF, had Tac IPV equal to or greater than 25%. According to Epocrates®, Tac C0 was higher in patients with fewer than 6 DDIs at the sixth- and twelfth-months post-transplantation, though there was no difference in Tac C0/D. The present study suggests that integrating data from multiple databases may enhance the uniformity and reliability of DDIs information across various sources.