Tacrolimus (FK506): Safety and Applications in Reconstructive Surgery

Tacrolimus (FK506) is a macrolide immunosuppressive drug that is approved for the prevention of allograft rejection. It is a standard component of immunosuppressive regimens currently in use for organ and reconstructive tissue transplants. The experimental literature has demonstrated potential efficacy in the management of other diseases for which transplantation does not play a role. The ability of tacrolimus to modulate the immune system and inhibit T cell activation provides a potential benefit for the treatment of disorders in which autoimmune phenomena are central to their pathogenesis such as rheumatoid arthritis and inflammatory bowel disease. Tacrolimus also has well-established neuroprotective and neuroregenerative properties through both similar and different mechanisms that have been extensively demonstrated in both small and large animal models. However, as a potent immunosuppressive agent, it can cause serious adverse effects, some of which are irreversible and potentially life threatening. This article reviews its safety under different therapeutic requirements and applications in both allogeneic and autogenous tissue reconstruction

Tolerance and effects of FK506 (tacrolimus) on nerve regeneration: a pilot study.

In adults, the outcome of nerve suture and nerve autograft remains generally unsatisfactory. FK506 (tacrolimus), an immunosuppressant drug used in transplantation, has been reported in animal studies to enhance nerve regeneration. In hand transplantation patients, nerve regeneration was unexpectedly good and rapid, and this observation has been attributed to FK506. The present Phase II experiment investigated the tolerance to FK506 after nerve suture or autograft, and the potential effects of the drug on axonal regeneration. Following strict criteria, five patients were included in this study. Within 7 days of nerve repair (median, ulnar and sciatic transections), patients received FK506 (aiming for blood concentrations between 5 and 8 ng/ml) for a total duration of 60 days. The patients were carefully followed with clinical and biological monitoring in order to detect side-effects. A clinical and electrophysiological assessment of the effect of FK506 on nerve regeneration was conducted. No undesirable side-effect was observed during or after FK506 treatment, but one non-compliant patient discontinued treatment. There was no evident improvement of sensory, motor or functional recovery at the end of the follow-up period (average duration 39.8 months), as compared to the expected clinical result without treatment. Although statistically non-significant, FK506 seemed to accelerate the progression of the Hoffmann-Tinel sign, but without impact on the final result.Clinical Trial, Phase IIJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe