What is Tacrolimus (FK506)?

From the Guidelines

Tacrolimus is a calcineurin inhibitor that plays a crucial role in preventing organ rejection in transplant patients, particularly in liver transplantation, by inhibiting T-cell activation and proliferation. It is available in various formulations, including oral capsules and extended-release tablets, with dosing regimens tailored to individual patient needs and blood concentration levels 1. The medication works by binding to FK-binding protein 12, inhibiting calcineurin, and preventing IL-2 gene transcription, thereby reducing T-cell activation and proliferation 1.

Key Characteristics of Tacrolimus

• Mechanism of action: Inhibition of calcineurin, preventing T-cell activation and proliferation 1
• Formulations: Oral capsules, extended-release tablets, topical ointments, and injectable forms 1
• Dosing: Highly individualized, based on transplanted organ, patient weight, and blood concentration levels, with regular monitoring through blood tests 1
• Side effects: Kidney problems, tremors, headache, high blood pressure, diabetes, and increased infection risk 1

Clinical Use and Recommendations

• Liver transplantation: Tacrolimus is the preferred calcineurin inhibitor, used in almost 90% of liver transplanted patients, due to its efficacy in reducing mortality, graft loss, and rejection 1
• Dosing and monitoring: Regular blood tests are necessary to maintain optimal blood levels and minimize toxicity 1
• Combination therapy: Tacrolimus is often used in combination with other immunosuppressive agents, such as antimetabolites, to reduce the risk of rejection and minimize side effects 1

Important Considerations

• Generic formulations: While generic tacrolimus formulations are available, caution is advised when switching from brand-name to generic formulations, and regular monitoring is necessary to ensure therapeutic equivalence 1
• Interactions and precautions: Patients taking tacrolimus should avoid grapefruit products and certain medications that can interact with it, and careful management by transplant specialists is necessary to maintain the delicate balance between preventing rejection and avoiding toxicity 1

From the FDA Drug Label

Tacrolimus, previously known as FK506, is the active ingredient in Tacrolimus capsules, USP. Tacrolimus is a calcineurin-inhibitor immunosuppressant produced by Streptomyces tsukubaensis Tacrolimus is a calcineurin-inhibitor immunosuppressant previously known as FK506. It is produced by Streptomyces tsukubaensis 2.

• Key points:
  • Immunosuppressant: Tacrolimus is used to suppress the immune system.
  • Calcineurin-inhibitor: It works by inhibiting the calcineurin enzyme.
  • Produced by: Streptomyces tsukubaensis.
• Main use: Tacrolimus is used for the prophylaxis of organ rejection in patients receiving allogeneic liver, kidney, or heart transplants 2.

From the Research

Definition and Mechanism of Tacrolimus

• Tacrolimus, also known as FK506, is an immunosuppressant agent that acts by inhibiting calcineurin 3.
• It is used as a therapeutic alternative to cyclosporin and represents a cornerstone of immunosuppressive therapy in organ transplant recipients 3.

Clinical Use of Tacrolimus

• Tacrolimus is widely used to prevent acute rejection following solid-organ transplantation, particularly in kidney transplantation 4.
• It has been evaluated as immunosuppressive therapy in patients with a variety of solid organ transplants, including liver, heart, lung, pancreas, and intestinal transplants 5.
• Tacrolimus has been shown to be effective in preventing episodes of acute rejection and allowing reduction of corticosteroid use 5.

Efficacy and Safety of Tacrolimus

• Extensive clinical use has confirmed that tacrolimus is a key option for immunosuppression after transplantation, with efficacy at least as good as or better than cyclosporin microemulsion in terms of patient and graft survival, treatment failure rates, and incidence of biopsy-proven acute and corticosteroid-resistant rejection episodes 6.
• However, tacrolimus has a higher incidence of diabetes mellitus, neurotoxicity, and nephrotoxicity compared to cyclosporin, while cyclosporin has a higher incidence of significant hypertension, hyperlipidaemia, hirsutism, and gingival hyperplasia 5, 3, 6.

Extended Release Formulation of Tacrolimus

• An extended release formulation of tacrolimus (Advagraf, Astagraf XL) allows for once-daily dosing, with the potential to improve adherence 7.
• The extended release formulation has a similar safety and efficacy profile to the traditional twice-daily formulation, but is not recommended for use in liver transplant patients due to increased risk of mortality in female recipients 7.