The Association of Tacrolimus Formulation Switching with Trough Concentration Variability: A Retrospective Cohort Study of Tacrolimus Use Post-Kidney Transplantation Based on National Drug Code (NDC) Numbers

Adv Ther. 2019 Jun;36(6):1358-1369. doi: 10.1007/s12325-019-00950-5. Epub 2019 Apr 19.

Abstract

Introduction: It was hypothesized that patients experiencing at least one tacrolimus formulation switch may require more frequent therapeutic drug monitoring, subsequent dose adjustments, and a potential for untoward clinical outcomes than patients who remain on a single formulation.

Methods: Eligible patients were adult kidney transplant recipients with stable renal function at month 3 post-transplant and no evidence of acute rejection, receiving an oral, tacrolimus-based regimen. Patients were categorized into two groups (fixed or variable formulation) using the US National Drug Code (NDC) on the basis of tacrolimus formulation usage over the 12-month period.

Results: A total of 305 patients were enrolled from four US transplant centers; 44 (14.4%) received multiple formulations and 261 (85.6%) received a single formulation. Mean number of tacrolimus dose adjustments and mean cumulative milligram dose change were not statistically different between the two groups. Mean trough-to-dose ratio, frequency of trough level measurements, and mean number of excursions above 120% or below 80% of the patient's mean trough concentration were significantly higher in the variable compared to the fixed formulation group.

Conclusion: A variable tacrolimus formulation regimen was associated with a higher frequency of trough level measurements and a greater number of excursions in trough levels compared with continuing on a fixed formulation regimen of tacrolimus in this retrospective chart review study.

Funding: Astellas Pharma Global Development, Inc. Plain language summary available for this article.

Keywords: Assessment; Bioequivalence; Electronic medical record; Kidney transplantation; Nephrology; Patient outcomes; Retrospective study; Tacrolimus; Therapeutic drug monitoring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Drug Compounding / standards*
  • Drug Monitoring / standards*
  • Female
  • Graft Rejection / drug therapy*
  • Graft Rejection / prevention & control*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Tacrolimus / therapeutic use*
  • United States

Substances

  • Immunosuppressive Agents
  • Tacrolimus

Associated data

  • figshare/10.6084/m9.figshare.7937948