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Tacrolimus has also proven effective in treating several autoimmune diseases. Despite its effectiveness, the use of tacrolimus has been characterized by challenges related to its narrow therapeutic index\u2014particularly in kidney transplantation\u2014necessitating frequent blood monitoring and dose adjustments. In recent years, improved extended-release formulations have made strides in reducing toxic effects, such as neurotoxicity and nephrotoxicity, and enhancing medication adherence. However, there remains considerable room for improvement, which has the potential to ameliorate long-term graft outcomes and decrease the burden of pill intake, especially for vulnerable patient populations. Recent advances enabling very-extended oral drug delivery present potential opportunities to optimize the peak-trough effects of tacrolimus-based immunosuppression, while also benefitting from the synergy of drug compounding and minimizing pill burden. In this article, we review the history of tacrolimus as a cornerstone of immunosuppression in kidney transplantation, the iterative improvements in outcomes and patient quality-of-life enabled by increasingly extended-release formulations, and the potential outlook for very-extended release formulations in the future.<\/jats:p>","DOI":"10.1177\/08971900261427132","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T13:52:57Z","timestamp":1772459577000},"page":"559-570","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Tacrolimus in Solid Organ Transplantation: Historical Impact, Current Use, and Future Directions in Immunosuppression"],"prefix":"10.1177","volume":"39","author":[{"given":"Rebecca","family":"Dieter","sequence":"first","affiliation":[{"name":"Transplant Institute, NYU Langone Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7309-308X","authenticated-orcid":false,"given":"Ian S.","family":"Jaffe","sequence":"additional","affiliation":[{"name":"Transplant Institute, NYU Langone Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aprajita","family":"Mattoo","sequence":"additional","affiliation":[{"name":"Transplant Institute, NYU Langone Health"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1390055"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(78)91970-0"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(79)92440-1"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198310063091401"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198605083141904"},{"issue":"1","key":"e_1_3_4_7_2","first-page":"465","article-title":"Cadaveric renal transplantation with Cyclosporin-A and steroids","volume":"15","author":"Hakala TR","year":"1983","unstructured":"Hakala TR, Starzl TE, Rosenthal JT, Shaw B, Iwatsuki S. 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