Methods: This retrospective cohort study examined the real world use of TDM and the effect on dose adjustment in inpatients ≥18 years old who were dispensed at least one dose of VOR (IV or Oral) with diagnosis, laboratory, and pharmacy data in Cerner Health Facts® database between 01/09-12/13. Therapeutic range for VOR was between 2-5.5 mg/L (Troke et al 2011).
Results: Of the 4,115 VOR exposed patients in the cohort, only 149 (4%) had TDM performed. Patients with TDM were younger (mean age 48 vs. 55), had longer LOS, were more likely to have oral administration, ICU admission, Aspergillosis infection, sepsis, renal failure, neutropenia, pneumonia, respiratory failure, GI hemorrhage and intestinal obstruction compared to patients without TDM. In addition, TDM was more likely to be performed in teaching hospitals and hospitals with at least 500 beds. Of the 149 patients who had TDM performed, 33% (n=49) were found to have subtherapeutic levels and 23% (n=34) were found to have supratherapeutic levels. Only 15% of those with TDM had a subsequent dose adjustment that followed as expected from TDM results, while 37% of those with TDM had a subsequent dose that did not follow from TDM results and 48% of TDM had only one dose of VOR. Associations between nontherapeutic levels and AEs were observed - mental abnormalities and concomitant use of inducing drugs were more likely with subtherapeutic levels, GI problems were less likely with therapeutic levels, and mortality was more likely with supratherapeutic levels.
Conclusion: Despite the expectation that TDM may improve efficacy and limit AEs associated with VOR use, this study reveals infrequent use of TDM in clinical practice. Also when TDM was performed, dose adjustments following nontherapeutic results were inconsistent. Thus, current practice in the US of monitoring VOR levels and subsequent dose adjustment when indicated is generally insufficient to meet the goal of achieving therapeutic levels.
Merck & Co Inc:
S. Marcella, Merck: Employee , Salary
D. Zhang, Merck Co. & Inc.: Employee , Salary