What is the recommended dosage and monitoring for Tacrolimus (FK506) in preventing organ rejection in transplant patients?

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Last updated: June 10, 2025 • View editorial policy

From the Guidelines

Tacrolimus trough levels should be kept at 6-10 ng/ml during the first month followed by 4-8 ng/ml thereafter. This recommendation is based on the most recent and highest quality study available, which emphasizes the importance of maintaining optimal tacrolimus levels to prevent organ rejection while minimizing the risk of adverse effects 1.

Key Considerations for Tacrolimus Use

  • The dosage of tacrolimus should be individualized based on the specific organ transplanted and patient factors.
  • Target trough blood levels may vary by transplant type and time post-transplant.
  • More intensive monitoring is required immediately post-transplant, with blood level measurements taken 2-3 times weekly, gradually decreasing to monthly or quarterly once stable.
  • Kidney function, electrolytes (particularly potassium and magnesium), blood glucose, blood pressure, and neurological status should be regularly monitored due to the potential for tacrolimus to cause nephrotoxicity, electrolyte disturbances, hyperglycemia, hypertension, and neurotoxicity.
  • Liver function tests should also be monitored periodically.

Drug Interactions and Monitoring

  • Tacrolimus is metabolized through the CYP3A4 system, and drugs that affect this system can alter tacrolimus concentrations.
  • Monitoring for drug/drug interactions is crucial, and adjustments in tacrolimus dosage may be necessary when using medications that interact with it through the CYP3A4 pathway, including certain antifungals, antibiotics, and anticonvulsants 2.
  • Patients should maintain consistent timing of doses and relation to meals, as food (particularly high-fat meals) can affect absorption.

Combination Therapy

  • It is recommended to combine tacrolimus with other immunosuppressive drugs (such as MMF, AZA, or mTORi) to allow for a lower range of tacrolimus trough levels than recommended for monotherapy and to help preserve renal function 1.
  • The administration of basiliximab induction with delayed introduction of tacrolimus is strongly recommended in patients at risk of developing post-transplant renal dysfunction 1.

From the FDA Drug Label

The initial oral tacrolimus capsule dosage recommendations for adult patients with kidney, liver, or heart transplants and whole blood trough concentration range are shown in Table 1

Table 1. Summary of Initial Oral Tacrolimus Capsules Dosage Recommendations and Whole Blood Trough Concentration Range in Adults

Patient Population | Tacrolimus Capsules | Initial Oral Dosage | Whole Blood Trough Concentration Range --- | --- | --- | --- Kidney Transplant With Azathioprine | 0.2 mg/kg/day, divided in two doses, administered every 12 hours | Month 1 to 3: 7 to 20 ng/mL, Month 4 to 12: 5 to 15 ng/mL Kidney Transplant With MMF/IL-2 receptor antagonist | 0.1 mg/kg/day, divided in two doses, administered every 12 hours | Month 1 to 12: 4 to 11 ng/mL Liver Transplant With corticosteroids only | 0.10 to 0.15 mg/kg/day, divided in two doses, administered every 12 hours | Month 1 to 12: 5 to 20 ng/mL Heart Transplant With azathioprine or MMF | 0.075 mg/kg/day, divided in two doses, administered every 12 hours | Month 1 to 3: 10 to 20 ng/mL, Month ≥ 4: 5 to 15 ng/mL

Therapeutic drug monitoring (TDM) is recommended for all patients receiving tacrolimus [see Dosage and Administration (2.6)].

The recommended dosage and monitoring for Tacrolimus (FK506) in preventing organ rejection in transplant patients are as follows:

  • Initial Oral Dosage: The initial oral dosage of tacrolimus capsules varies depending on the type of transplant and the patient population, ranging from 0.075 mg/kg/day to 0.2 mg/kg/day, divided in two doses, administered every 12 hours.
  • Whole Blood Trough Concentration Range: The whole blood trough concentration range for tacrolimus also varies depending on the type of transplant and the patient population, ranging from 4 to 20 ng/mL.
  • Therapeutic Drug Monitoring (TDM): TDM is recommended for all patients receiving tacrolimus to evaluate rejection, toxicity, dose adjustments, and compliance.
  • Monitoring Frequency: The frequency of monitoring should be individualized based on factors such as hepatic or renal dysfunction, the addition or discontinuation of potentially interacting drugs, and the post-transplant time.
  • Key Considerations:
    • African-American patients may require higher doses compared to Caucasians.
    • Patients with renal impairment may require lower doses.
    • Patients with hepatic impairment may require lower doses and close monitoring of blood concentrations.
    • Concomitant adrenal corticosteroid therapy is recommended early post-transplantation.
    • Anaphylactic reactions have occurred with injectables containing castor oil derivatives, such as tacrolimus injection, and monitoring for signs and symptoms of anaphylaxis is recommended 3, 4.

From the Research

The recommended dosage and monitoring for Tacrolimus (FK506) in preventing organ rejection in transplant patients are crucial for its effective use. Key points to consider include:

  • Tacrolimus has potent immunosuppressive qualities that prevent rejection, with straightforward dosing and generally good tolerance 5.
  • The drug is approved for prophylaxis of transplant rejection in liver, kidney, or heart allograft recipients and for the treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal products 6.
  • Monitoring is essential to ensure proper dosage and limit potential harmful adverse effects, such as renal damage, neurotoxicity, and other serious adverse events 7.

Dosage and Administration

  • Tacrolimus has become the calcineurin inhibitor of choice for the prevention of rejection in renal transplantation, with numerous clinical trials showing its superiority to cyclosporine in preventing acute rejection 8.
  • A novel once-daily dosage form of tacrolimus has been developed and is approved for use in Europe, which may improve compliance and possibly long-term outcomes 8.
  • The use of tacrolimus in renal transplant recipients is associated with a reduced risk for acute rejection, a reduction in the occurrence of steroid-resistant rejection, and better graft function compared to cyclosporine 6.

Monitoring and Adverse Effects

  • Frequent and diligent monitoring by physicians is required to ensure proper dosage and limit the potential for harmful adverse effects 7.
  • Adverse effects of tacrolimus can include calcineurin inhibitor nephrotoxicity, post-transplant diabetes mellitus, arterial hypertension, neurotoxicity, and neutropenia 5, 6, 9.
  • Tacrolimus-induced neutropenia is a less recognized but potentially harmful complication that can be managed by discontinuation of tacrolimus and switching to cyclosporine 9.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Tacrolimus in transplant rejection.

Expert opinion on pharmacotherapy, 2013

Research

The role of tacrolimus in renal transplantation.

Expert opinion on pharmacotherapy, 2008

Research

Tacrolimus-induced neutropenia in renal transplant recipients.

Clinical journal of the American Society of Nephrology : CJASN, 2011

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.