What is the target therapeutic trough level of Tacrolimus (Immunosuppressant)?

From the Guidelines

The target therapeutic trough level of Tacrolimus is 6-10 ng/ml during the first month, followed by 4-8 ng/ml thereafter.

Key Points

• The trough levels of Tacrolimus should be monitored closely to avoid adverse effects and ensure adequate immunosuppression 1.
• The recommended trough levels may vary depending on the individual patient's response and the presence of other immunosuppressive agents 1.
• Tacrolimus is often used in combination with other immunosuppressants, such as mycophenolate mofetil (MMF) or azathioprine (AZA), to allow for lower trough levels and reduce the risk of renal dysfunction 1.
• The use of basiliximab induction and delayed introduction of Tacrolimus is recommended in patients at risk of post-transplant renal dysfunction 1.
• Long-term survivors can maintain normal liver tests with Tacrolimus levels substantially lower than the recommended thresholds, but this should be done with caution and close monitoring to avoid subclinical rejection 1.

Evidence Summary

The evidence from the provided studies suggests that the target therapeutic trough level of Tacrolimus is 6-10 ng/ml during the first month, followed by 4-8 ng/ml thereafter 1. This is supported by the European Association for the Study of the Liver (EASL) clinical practice guidelines on liver transplantation, which recommend these trough levels for Tacrolimus monotherapy 1. The use of combination regimens, including Tacrolimus with other immunosuppressants, may allow for lower trough levels and reduce the risk of renal dysfunction 1. However, the optimal Tacrolimus levels when using combination regimens are not well established, and trough levels should be individualized based on the patient's response and the presence of other immunosuppressive agents 1.

From the FDA Drug Label

Most patients are stable when trough whole blood concentrations are maintained between 5 to 20 ng/mL. Long-term post-transplant patients are often maintained at the low end of this target range. The protocol-specified target tacrolimus whole blood trough concentrations (Ctrough,Tac) in Study 2 were 7 to 16 ng/mL for the first three months and 5 to 15 ng/mL thereafter. Approximately 80% of patients maintained tacrolimus whole blood trough concentrations between 6 to 16 ng/mL during months 1 through 3 and, then, between 5 to 12 ng/mL from month 4 through 1 year.

The target therapeutic trough level of Tacrolimus is 5 to 20 ng/mL, with long-term post-transplant patients often maintained at the low end of this range. In some studies, the target range was 7 to 16 ng/mL for the first three months and 5 to 15 ng/mL thereafter 2, 2.

From the Research

Target Therapeutic Trough Level of Tacrolimus

The target therapeutic trough level of Tacrolimus, an immunosuppressant, can vary depending on the specific context and patient population. Based on the available evidence, the following points can be noted:

• A study published in 2020 3 found that a target trough concentration of 4-7 ng/mL during the first month after liver transplantation is safe and improves graft and renal function.
• A 2023 study 4 suggested that higher tacrolimus trough levels and time in the therapeutic range are associated with the risk of acute rejection in the first month after renal transplantation, with a target range of 7-12 ng/mL.
• Another study from 2021 5 developed a population pharmacokinetic model for predicting the initial doses of the once-daily prolonged release tacrolimus Envarsus in adult kidney recipients, with a target trough level range of 3-7 ng/mL.
• A 2024 retrospective multicenter real-world evidence study 6 found that tacrolimus levels of 5.0-7.9 ng/mL and 5.0-6.9 ng/mL during the 2-12 month and 12-72 month post-transplantation periods, respectively, were associated with reduced risks of composite allograft outcomes.
• A 2017 study 7 found that average tacrolimus trough levels in the first month after transplantation may predict acute rejection, with a target level of ≥8 ng/mL.

Key Findings

• The target therapeutic trough level of Tacrolimus can vary depending on the specific context and patient population.
• A range of 4-7 ng/mL has been suggested for liver transplantation 3, while a range of 7-12 ng/mL has been suggested for renal transplantation 4.
• A population pharmacokinetic model has been developed to predict the initial doses of Envarsus in adult kidney recipients, with a target trough level range of 3-7 ng/mL 5.
• Tacrolimus levels of 5.0-7.9 ng/mL and 5.0-6.9 ng/mL have been associated with reduced risks of composite allograft outcomes in kidney transplantation 6.
• Average tacrolimus trough levels in the first month after transplantation may predict acute rejection, with a target level of ≥8 ng/mL 7.

Trough Level Ranges

• 4-7 ng/mL: suggested for liver transplantation 3
• 7-12 ng/mL: suggested for renal transplantation 4
• 3-7 ng/mL: target range for Envarsus in adult kidney recipients 5
• 5.0-7.9 ng/mL and 5.0-6.9 ng/mL: associated with reduced risks of composite allograft outcomes in kidney transplantation 6
• ≥8 ng/mL: target level for predicting acute rejection 7