Assessment of Clinically Relevant Drug Interactions by Online Programs in Renal Transplant Recipients

Potential drug-drug interactions (pDDIs) with immunosuppressive drugs are frequently observed in renal transplant recipients. Drug interaction programs are acknowledged as a fundamental tool to alert physicians to pDDIs, but there is a high concern about variation among different programs in terms of quality and reliability of information.

To (a) characterize the difference in severity levels of pDDIs with tacrolimus and cyclosporine provided by 3 drug interaction programs and (b) identify clinically relevant DDIs with these immunosuppressive drugs in renal transplant recipients.

This study was conducted in a nephrology outpatient clinic at the University Research & Training Hospital between November 2017 and February 2018. A clinical pharmacist attended clinic visits with physicians and evaluated drug interactions. Micromedex, Medscape, and Lexicomp drug interaction programs were used to identify pDDIs and their severities. Furthermore, Drug Interaction Probability Scale (DIPS) criteria were applied to identify clinically relevant drug interactions seen in clinic patients. Finally, a clinical pharmacist intervened to manage clinically relevant drug interactions identified by DIPS.

80 patients (54 under tacrolimus; 26 under cyclosporine treatment) were included in this study. The 3 drug interaction programs generated 648 pDDIs, 63 of which were different drug interaction pairs. Ninety-eight pDDIs were common to all 3 drug interaction programs. Sixty-three different drug interaction pairs were evaluated according to severity level, and 3 drug interaction pairs were at the same level (moderate) among the programs. The Fleiss' kappa overall interrater agreement was poor. The kappa revealed a moderate agreement for interaction pairs with a "severe" rating and a slight agreement for interaction pairs with a "major" rating. According to the DIPS evaluation, 11 pDDIs were classified as "possible," and the percentage of clinically relevant drug-drug interactions was 4.0% (10/248), 4.2% (11/265), and 8.2% (11/135) for Medscape, Lexicomp, and Micromedex, respectively. Although daily doses of immunosuppressive drugs were not changed, the blood concentrations of these drugs increased after administration of an interacting drug. As a result, in order to maintain normal therapeutic range of concentrations, dose reduction or drug change was applied where appropriate.

Interaction checker programs are commonly used by health institutions, since they provide quick and summarized information on mechanism and management of drug interactions, when no clinical pharmacist is present to interpret. However, the likelihood of detecting clinically relevant DDIs by interaction checker programs is relatively low, and there are inconsistencies among different programs. Individualized patient monitoring should be maintained by a multidisciplinary health care team that includes a clinical pharmacist, and decision making should be based on professional assessment of the renal transplant patient.

No outside funding supported this study. The authors have no conflicts of interest to disclose.