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Postmarket: Evaluation of Generic Drug Product Substitution


In 2014, OGD funded two research grants seeking to better understand the substitutability of generic tacrolimus products and their effects on transplant outcomes and adherence to the medication regimen. Retrospective data analyses of existing databases and a prospective evaluation of clinical outcomes in patients using tacrolimus products as clinically indicated are the main objectives of these two research projects.


To better understand the usage patterns of generic drug products in postmarketing, two other research grants focusing on authorized generic drugs were initiated during the same year. In these studies, analyses of the available claims databases will be performed to characterize and compare substitution and switchback rates, adherence, medical utilization, and clinical outcomes of authorized generics and other generic drug products as well as select brand-name drug products. These research studies will provide information on generic drug usage patterns and will help to identify factors influencing generic drug use.

Figure 1. Metabolic pathway of tacrolimus

Figure 1. Metabolic pathway of tacrolimus

The sites of metabolism are numbered in the tacrolimus structure and are indicated by an arrow in the corresponding metabolite structures. Note: 13-DMT and 12-HT undergo furan ring rearrangement. Reproduced from Yang Dai,  Mary F. Hebert, Nina Isoherranen, Connie L. Davis, Christopher Marsh, Danny D. Shen, and Kenneth E. Thummel, Effect of CYP3A5 polymorphism on tacrolimus metabolic clearance in vitro, Drug Metab Dispos 34:836-847 (May 2006)

ORS staff facilitating research in this area

  • Oluwamurewa Oguntimein, Larissa Lapteva, Kimberly Witzmann

Projects and Collaborators

  • Retrospective analysis on the impact of generic immunosuppressants on acute rejection and long term graft survivals.
    • Site PI: Alan Leichtmann, Arbor Research Collaborative for Health
    • Grant #: 1 U01FD005274-1
  • Prospective study comparing brand and generic immunosuppression on transplant outcomes, adherence and immune response.
    • Site PI: Suphamai Bunnapradist, University of California Los Angeles
    • Grant #: 1U01FD005271-01
  • Postmarket surveillance evaluation of authorized generic drug products.
    • Site PI: Joshua Gagne, Brigham and Women's Hospital
    • Grant #: 1U01FD005279-1
  • Postmarket surveillance evaluation of authorized generic drug products.
    •  Site PI: Richard Hansen, Auburn University
    • Grant #: 1U01FD005272-1

Publications and Presentations

  • Title of Presentation: Assessing the Association of Four Measurements of Adherence to Tacrolimus for Organ Transplant Recipients
    • Presenter: John Peipert
    • Location and Date: The 2015 Pittsburgh Conference on the Science of Medication Adherence. June 2-3, 2015.


  • Research projects in progress


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