What is the trough level with Envarsus (tacrolimus)?

From the Guidelines

Trough levels with Envarsus (tacrolimus) should be maintained at 6-10 ng/ml during the first month, followed by 4-8 ng/ml thereafter. This is based on the strong recommendation from the EASL clinical practice guidelines on liver transplantation 1.

Key Considerations

• The target trough levels may vary depending on the individual patient's risk factors and clinical condition, such as the presence of kidney dysfunction or advanced liver failure 1.
• Combination regimens with other immunosuppressants, such as mycophenolate mofetil (MMF) or azathioprine (AZA), may allow for lower tacrolimus trough levels, typically below 4-7 ng/ml during the first month and 3-5 ng/ml thereafter 1.
• Regular monitoring of kidney function, liver function, and blood glucose levels is crucial to minimize potential side effects and adjust the dose accordingly.
• Dose adjustments should be made cautiously, as small changes can significantly impact trough levels, with increases or decreases of 0.5-1 mg every 3-7 days as needed.

Important Factors to Consider

• Patient-specific factors, such as pre-existing kidney dysfunction, advanced liver failure, hyponatremia, or high BMI, may require adjustments to the target trough levels or the use of alternative immunosuppressive regimens 1.
• The use of basiliximab induction and delayed introduction of tacrolimus may be beneficial in patients at risk of post-transplant renal dysfunction 1.
• Long-term survivors may be able to maintain normal liver tests with tacrolimus levels substantially lower than the recommended thresholds, but this should be done with caution and close monitoring for subclinical rejection 1.

From the FDA Drug Label

In the European trial, the cyclosporine trough concentrations were above the pre-defined target range (i.e., 100 to 200 ng/mL) at Day 122 and beyond in 32% to 68% of the patients in the cyclosporine treatment arm, whereas the tacrolimus trough concentrations were within the pre-defined target range (i.e., 5 to 15 ng/mL) in 74% to 86% of the patients in the tacrolimus treatment arm.

The trough level for Envarsus (tacrolimus) is 5 to 15 ng/mL 2.

From the Research

Trough Level with Envarsus (Tacrolimus)

• The trough level with Envarsus (tacrolimus) can vary depending on the patient population and the specific study, but some studies provide guidance on target trough levels 3, 4, 5, 6, 7.
• A study on de novo kidney transplant patients using Envarsus found that a personalized dosing strategy based on a population pharmacokinetic model could improve the early attainment of therapeutic trough levels, with a target range not explicitly stated in the study 3.
• Another study on liver transplant patients found that a target trough concentration of 4-7 ng/mL during the first month after liver transplantation was safe and improved graft and renal function 4.
• A study on renal transplant patients found that a mean tacrolimus level > 7 ng/mL was associated with a decreased risk of acute rejection, and that every 10% increase in time in the therapeutic range was associated with a 28% lower risk of acute rejection 5.
• A study comparing 4-hour monitoring to trough monitoring in liver transplant patients found that the target range for 4-hour levels was 7.8-16 ng/ml, which was calculated to be comparable to a target trough range of 4-8 ng/ml 6.
• An observational retrospective study on stable renal transplant patients converted to Envarsus found that the median trough concentrations were 6.4 ng/mL and 6.3 ng/mL for patients previously on Prograf and Advagraf, respectively, with a significant reduction in daily dose 7.