Precision medicine for tacrolimus dosing in heart transplant recipients

Document Type

Conference Proceeding

Publication Date


Publication Title

J Heart Lung Transplant


Purpose: Interpatient variability in tacrolimus requirements are large and influenced by multiple factors including cytochrome P450 (CYP) genetics, specifically by CYP3A5 and to a lesser extent CYP3A4. Tacrolimus dosing tailored to CYP genotype has been shown to shorten time to therapeutic range in kidney transplant but data in heart transplantrecipients is sparse and findings are variable. We recently implemented weight and genotype-based initial tacrolimusdosing in our heart transplant program. The objective of this study is to examine the impact of genetically tailored tacrolimus dosing on achieving therapeutic trough levels. Methods: This is a retrospective cohort study of adult hearttransplant recipients from January 2014 to August 2017. Patients were divided into the standarddosing cohort (those transplanted between January 2014 and October 2015) or the genetic tailored-dosing cohort (those transplanted after policy implementation in October 2015). Patients who received multiple organ transplantations, switched to cyclosporine therapy, or did not have data for the entire study period were excluded. The primary endpoint was days to a therapeutic tacrolimus trough level (10-15 ng/mL). The key secondary endpoint was the percentage of tacrolimus levels within range over the first month after transplant. These were compared between groups using Student's t-test. Results: In total, 63 patients met inclusion criteria, 28 patients prior to the policy change (standard-dose group) and 35 patients after the policy change (tailored-dose group). There were no differences between groups in terms of age, sex, race, or body mass index (p= NS). The tailored-dose group had a nearly 3 day sooner average time to therapeutic range (4.5 ± 2.6 days) compared to the standard-dosing group (7.3 ± 4.7 days) which was statistically significant (p= 0.0067). Similarly, the tailored-dosing group had on average a greater proportion of days within the therapeutic window at 40% compared to an average of 31% in the standard-dosing group (p= 0.01). Conclusion: Personalized tacrolimus dosing was feasible, shortened the time to achieve therapeutic levels, and increased the proportion of tacrolimus levels within therapeutic trough range.





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