Clinical Information

Tacrolimus is a macrolide antibiotic derived from the fungus Streptomyces tsukubaensis. Like cyclosporine, tacrolimus inhibits calcineurin to suppress T cells. Tacrolimus is metabolized by cytochrome P450 (CYP) 3A4; thus, its concentrations are affected by drugs that inhibit (calcium channel blockers, antifungal agents, some antibiotics, grapefruit juice) or induce (anticonvulsants, rifampin) this enzyme. Tacrolimus has a narrow therapeutic range, and adverse effects are common, particularly at high doses and concentrations, making therapeutic drug monitoring essential.

Since 90% of tacrolimus is in the cellular components of blood, especially erythrocytes, whole blood is the preferred specimen for analysis of trough concentrations. Target steady-state concentrations vary depending on clinical protocol, the presence or risk of rejection, time from transplant, type of allograft, concomitant immunosuppression, and side effects (mainly nephrotoxicity). Optimal trough blood concentrations are generally between 5.0 and 15.0 ng/mL. Higher levels are often sought immediately after transplant, but as organ function stabilizes at about 4 weeks from transplant, doses are generally reduced in stable patients for most solid organ transplants. Trough concentrations should be maintained below 20 ng/mL.