Potential drug-drug interactions of immunosuppressants in kidney transplant recipients: comparison of drug interaction resources

Abstract

Background Drug-drug interactions are frequently observed in kidney transplant recipients due to polypharmacy and use of immunosuppressants. However, there is only one study evaluating clinically relevant potential drug-drug interactions of immunosuppressants specially in kidney transplant recipients by means of online databases and Stockleys Drug Interactions, as a gold standard. Aim This study aimed to compare four online databases used frequently to determined clinically relevant potential drug-drug interactions of immunosuppressants in kidney transplant recipients according to the Renal Drug Handbook. Method This was a descriptive cross-sectional study conducted between October 1, 2019, and March 18, 2020, in the nephrology ward of Ankara University School of the Medicine, Ibn-i Sina Hospital. In total, 52 adult patients' discharge prescriptions were retrieved from their medical records and analyzed retrospectively. Micromedex (R), Lexicomp (R), Medscape, and Drugs.com databases were used to evaluate drug interactions. The Renal Drug Handbook was used as a gold standard to do specificity and sensitivity analysis. Results A total of 127 potential drug-drug interactions between the immunosuppressants and co-medications were detected by at least one online database. 32 (25.2%) of these were approved as clinically relevant potential drug-drug interactions by the Renal Drug Handbook. Lexicomp (R) and Drugs.com have exhibited the highest sensitivity (0.72 and 0.75) while Micromedex (R) has shown the highest specifity (0.83). Furthermore, the highest positive predictive value has been observed in Micromedex (R) (0.53). Micromedex (R) and Medscape had the highest negative predictive value (0.83 and 0.82). However, the kappa value of all was low. The values of inter-rater agreement (Kappa index) between online databases and the Renal Drug Handbook were weak (range 0.05-0.36). In addition, only 11 (8.7%) of potential drug-drug interactions were identified by all online databases. Conclusion This study showed that there was a weak compatibility between each database examined and the Renal Drug Handbook to detect clinically relevant potential drug-drug interactions for immunosuppressants in kidney transplant recipients. Therefore, we suggest that although databases might be practical to take a quick glance in detection of potential drug-drug interactions between immunosuppressants and co-medications, the data should be evaluated in detail and interpreted with caution in combination with a reference book like Renal Drug Handbook.