From the Guidelines
To prevent tacrolimus rebound, a gradual transition from intravenous to oral tacrolimus is recommended, starting oral tacrolimus 24 hours before discontinuing the infusion, with the first oral dose typically 2-4 times the hourly IV rate given as a daily total divided twice daily. This approach is supported by the most recent guidelines, which emphasize the importance of maintaining therapeutic immunosuppression during transition to prevent rejection episodes that could compromise graft function 1. The recommended tacrolimus trough levels during the first month are 6-10 ng/ml, followed by 4-8 ng/ml thereafter, and it is suggested to combine tacrolimus with other immunosuppressive drugs to allow for a lower range of tacrolimus trough levels and to help preserve renal function 1.
Some key points to consider when transitioning from intravenous to oral tacrolimus include:
- Starting oral tacrolimus 24 hours before discontinuing the infusion
- Using a first oral dose that is 2-4 times the hourly IV rate, given as a daily total divided twice daily
- Monitoring tacrolimus trough levels closely during transition, aiming for therapeutic levels based on transplant type and time post-transplant
- Adjusting oral doses based on levels measured 12 hours after the dose
- Being aware of the factors that can affect oral absorption, such as food intake, gastrointestinal function, and drug interactions
It is also important to note that the use of basiliximab induction and delayed introduction of tacrolimus is strongly recommended in patients at risk of developing post-transplant renal dysfunction, as assessed by the pre-existence of kidney dysfunction, advanced liver failure, hyponatremia or high BMI 1. Additionally, the benefits of managing patients on low tacrolimus levels in terms of reduced immunosuppression-related side effects have not been formally demonstrated and could be counteracted by the development of subclinical rejection, which should be investigated by monitoring donor-specific antibodies (DSAs) and transient elastography values, or by performing surveillance liver biopsies 1.
From the Research
Tacrolimus Drip Rebound
- The concept of tacrolimus drip rebound is not directly addressed in the provided studies 2, 3, 4, 5, 6.
- However, the studies discuss the importance of therapeutic drug monitoring (TDM) of tacrolimus to ensure proper dosage and minimize adverse effects 2, 3, 5, 6.
- Tacrolimus is a calcineurin inhibitor with a narrow therapeutic window, and its metabolism can be affected by various factors, making TDM crucial for optimal patient outcomes 2, 3.
- The studies also highlight the challenges of managing tacrolimus therapy, including the risk of renal damage, neurotoxicity, and other serious adverse events 3, 4.
- A pharmacist-led tacrolimus management protocol was shown to be effective in maintaining therapeutic drug levels and reducing the risk of adverse effects 5.
- The use of area under the curve (AUC) monitoring and Bayesian estimation can help optimize tacrolimus dosing and improve patient outcomes 6.
- Individualized C0 targets can be estimated to replace or complement AUC monitoring, allowing for more precise dosing and reduced risk of adverse effects 6.