tacrolimus

Tacrolimus is a macrolide immunosuppressant produced by the bacterium Streptomyces tsukubaensis. It is used systemically to prevent organ transplant rejection and, in topical form, to treat inflammatory skin conditions such as atopic dermatitis.

Tacrolimus binds to FKBP12 to form a complex that inhibits calcineurin, preventing NFAT dephosphorylation and reducing IL-2 transcription, thereby dampening T-cell activation.

It is highly lipophilic and metabolized mainly by the liver enzyme CYP3A4/5. Oral bioavailability is variable, and systemic exposure is primarily eliminated via biliary excretion. The half-life is approximately 12–18 hours, and dosing is adjusted based on trough blood concentrations.

Systemic tacrolimus is used to prevent rejection in kidney, liver, and heart transplantation and is typically given in combination with corticosteroids. Topical tacrolimus is applied as an ointment for atopic dermatitis and other inflammatory skin conditions. Dosing is individualized and requires regular trough monitoring.

Safety and interactions: systemic therapy can cause nephrotoxicity, neurotoxicity (such as tremor), hypertension, hyperglycemia, electrolyte disturbances, increased infection risk, and post-transplant malignancies. Topical use can cause local irritation, and systemic absorption can lead to broader adverse effects. Tacrolimus levels are increased by strong CYP3A4 inhibitors (for example certain azole antifungals and macrolide antibiotics) and decreased by inducers; grapefruit juice may raise exposure. Data in pregnancy are limited and use requires a risk-benefit assessment. Tacrolimus was approved for transplantation in 1994.