takrolimus

Takrolimus, also spelled tacrolimus, is a macrolide lactone immunosuppressant derived from the bacterium Streptomyces tsukubaensis. It acts as a calcineurin inhibitor after binding to the immunophilin FKBP12, forming a complex that blocks calcineurin. This prevents dephosphorylation of the nuclear factor of activated T-cells (NF-AT), reducing transcription of interleukin-2 and other cytokines and thereby suppressing T-cell activation.

Systemic tacrolimus is used to prevent organ transplant rejection, particularly in kidney, liver, and heart recipients, as part of a multi-drug immunosuppressive regimen. It is also used to prevent graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Topical tacrolimus ointment, commonly available as 0.03% and 0.1%, is approved for atopic dermatitis in adults and children and is used as a non-steroidal alternative in areas where steroids are undesirable.

Pharmacokinetics and interactions: oral tacrolimus has variable bioavailability and is extensively metabolized by hepatic cytochrome P450 3A4/5. Blood levels are monitored to guide dosing. Many drugs interact with tacrolimus by inhibiting or inducing CYP3A4, altering its concentrations.

Adverse effects and safety: systemic tacrolimus can cause nephrotoxicity and neurotoxicity, along with hypertension, hyperkalemia, hyperglycemia, and an increased risk of infections and malignancies (including skin cancer and lymphoma). Topical use may cause local burning or irritation; systemic absorption from topical formulations can occur. Careful monitoring is advised, and use during pregnancy requires a risk–benefit assessment.