Tacrolimus Levels and Correlation to Age and Weight Calculation

Background: Tacrolimus (FK) has become one of the key calcineurin inhibitors routinely used to reduce the risk of graft-versus-host-disease in patients undergoing allogeneic stem cell transplant (SCT). As non-ablative regimens have increased the number of transplants in the geriatric population, the data from initial studies may not accurately reflect our current transplant patients. Although the mechanism of action in elderly patients is similar, the metabolism and tolerability may be different. The narrow therapeutic index, drug interactions, and metabolism via the CYP450 pathway present unique challenges to achieving therapeutic drug levels. Current dosing at our institution relies exclusively on actual body weight (ABW) without taking into account age, gender, serum albumin, and ideal body weight (IBW). With this retrospective study, we explore the impact these factors may have on tacrolimus serum concentrations and associated toxicities. Methods: We performed a chart review of patients over the age of 18 who received tacrolimus as part of their allogeneic SCT at our center between 2014 and 2017. The following variables were obtained from the medical records: age, gender, ABW, height, IBW, initial FK dose, serum albumin, and FK trough levels within the first 2 weeks. Patients who did not have FK levels drawn within 5 days of starting treatment, those who received concomitant CYP inhibitors without dose adjustment, and those who died within 30 days from SCT were excluded. Results: Ninety-five patients met the criteria of which 59 were males and 36 females. Forty-six patients were supratherapeutic at first trough and 76 were supratherapeutic at either the first, second, or third level. Of the patients with supratherapeutic levels, 34.2% had clinical toxicity (n = 26). Male patients (P = .0006) and patients over age 65 (P = .0399) were more likely to be supratherapeutic at first tacrolimus trough. After adjusting for age and gender, the odds of having a supratherapeutic FK trough were 3.1 times higher for every .5 mg increase with ABW dosing (when using IBW as baseline). Conclusions: The current patient population undergoing allogeneic SCT requires a revised strategy for optimal care. The data presented here suggests male gender and age over 65 are predictive of having a supratherapeutic first FK trough which may favor the use of a lower starting dose. Similarly, the higher supratherapeutic events in patients with a greater difference between ideal and actual weights hints at improved dosing when the IBW is used in overweight patients. Our study suggests that age, gender, and IBW should be factored into tacrolimus dosing to prevent overtreatment and toxicities. Further prospective studies are needed to confirm these observations.