Abstract
Tacrolimus, the most widely used immunosuppressant derived from the fungus Streptomyces tsukubaensis, is essential in preventing rejection in solid organ transplants. It is reported to have neurotoxic effects in about 30% of the patients, which include tremors, headache, seizures, psychosis, loss of vision, posterior reversible encephalopathy syndrome (PRES), and coma. This systematic review, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, analyzed 13 high-quality studies between 2015 and 2025 identified from PubMed, ScienceDirect, MDPI, and Google Scholar, including observational studies and excluding case reports and articles not written in English. Pathogenesis involved in neurotoxicity is not fully understood but includes the disruption of the blood-brain barrier and the predisposing factors such as drug exposure, twice-daily dosing, CYP3A5 polymorphisms, older age, female sex, Black ethnicity, high model for end-stage liver disease (MELD) scores, pretransplant hemoglobin, and inflammatory markers such as C-reactive protein (CRP). Adverse effects are more frequently seen in the early post-transplant period, even at therapeutic levels, and are often associated with dose formulations and dose intervals. CYP3A5 polymorphisms for drug dosing and visual evoked potentials for optic neuropathy can be used as early subclinical markers. Management involves dose reduction or switching to cyclosporine, resulting in resolution of the symptoms. Future multi-center studies are needed to develop standardized diagnostics and personalized strategies to balance immunosuppression and neurological safety.