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

Int J Clin Pharm. 2022 Jun;44(3):651-662. doi: 10.1007/s11096-022-01385-9. Epub 2022 Mar 2.

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®, Lexicomp®, 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® and Drugs.com have exhibited the highest sensitivity (0.72 and 0.75) while Micromedex® has shown the highest specifity (0.83). Furthermore, the highest positive predictive value has been observed in Micromedex® (0.53). Micromedex® 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.

Keywords: Databases; Drug-drug interactions; Kidney transplant recipients; The renal drug handbook.

MeSH terms

  • Adult
  • Cross-Sectional Studies
  • Drug Interactions
  • Humans
  • Immunosuppressive Agents* / therapeutic use
  • Kidney Transplantation*
  • Retrospective Studies

Substances

  • Immunosuppressive Agents