What is the use of Tacrolimus (FK506)?

From the Guidelines

Tacrolimus is the preferred immunosuppressant for liver transplant patients due to its efficacy in reducing mortality, graft loss, and rejection compared to cyclosporine, as shown in a meta-analysis of 3813 patients 1. The mechanism of action of tacrolimus involves inhibiting calcineurin, which suppresses T-cell activation and prevents the immune system from attacking the transplanted organ.

• Typical dosing ranges from 0.05-0.1 mg/kg/day divided into two doses, with blood levels carefully monitored to maintain therapeutic concentrations (typically 5-15 ng/mL, though target ranges vary by transplant type and time since transplantation) 1.
• Tacrolimus is available in immediate-release capsules (Prograf) and extended-release formulations, with the latter providing once-daily dosing and similar efficacy and safety to the twice-daily formulation 1.
• Common side effects include nephrotoxicity, neurotoxicity, hypertension, diabetes, electrolyte abnormalities, and increased infection risk.
• Regular monitoring of tacrolimus blood levels, kidney function, blood pressure, blood glucose, and electrolytes is essential, as well as avoiding grapefruit products and certain medications that interact with tacrolimus, including some antifungals, antibiotics, and antiseizure medications, as these can significantly alter drug levels and increase toxicity risk.
• The use of generic tacrolimus formulations is considered safe, but precautions should be taken, including stringent therapeutic drug monitoring during the initial switch phase, due to the lack of proven bioequivalence between different generic compounds 1.

From the FDA Drug Label

Tacrolimus capsule is a calcineurin-inhibitor immunosuppressant indicated for the prophylaxis of organ rejection in adult patients receiving allogeneic liver, kidney, or heart transplants and pediatric patients receiving allogeneic liver transplants in combination with other immunosuppressants. (1.1)

The main use of Tacrolimus is for the prophylaxis of organ rejection in patients who have received a liver, kidney, or heart transplant. It is used in combination with other immunosuppressants.

• Key indications:
  • Adult patients receiving allogeneic liver, kidney, or heart transplants
  • Pediatric patients receiving allogeneic liver transplants 2 2

From the Research

Overview of Tacrolimus

• Tacrolimus is a potent immunosuppressive agent used to prevent rejection in solid organ transplant recipients 3, 4, 5.
• It has a narrow therapeutic range and requires careful dosing to achieve optimal exposure while minimizing toxicity 6, 7.

Clinical Efficacy

• Tacrolimus has been shown to be effective in preventing acute rejection and improving graft function in renal transplant recipients compared to cyclosporine 4, 5.
• It is also used to treat allograft rejection resistant to other immunosuppressive medications 4.

Administration and Dosing

• Tacrolimus can be administered orally or sublingually, with sublingual administration achieving comparable trough concentrations to oral administration 6.
• The sublingual:oral dosing ratio is approximately 1:2, but may vary depending on individual factors and concomitant medications 6.
• Genetic variation and other factors can influence an individual's response to tacrolimus treatment, highlighting the need for personalized dosing strategies 7.

Side Effects and Toxicity

• Tacrolimus can cause significant side effects, including nephrotoxicity and post-transplant diabetes mellitus 3, 4, 5.
• Long-term use of tacrolimus can lead to conditions such as calcineurin inhibitor nephrotoxicity 3.