{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T20:04:22Z","timestamp":1789070662233,"version":"build-2803163510"},"reference-count":9,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,4,3]],"date-time":"2014-04-03T00:00:00Z","timestamp":1396483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:p>Tacrolimus, a macrolide immunosuppressant, is used topically for the treatment of cutaneous manifestations of graft\u2010versus\u2010host disease (<jats:styled-content style=\"fixed-case\">GVHD<\/jats:styled-content>) for rapid, symptomatic relief of pruritus and erythema. Despite the manufacturer's product information reporting minimal systemic effects of topical tacrolimus, this has not been evaluated in patients with cutaneous <jats:styled-content style=\"fixed-case\">GVHD<\/jats:styled-content> and with occlusive dressings. We describe two patients with cutaneous <jats:styled-content style=\"fixed-case\">GVHD<\/jats:styled-content> who developed toxic tacrolimus levels after receiving several applications of tacrolimus ointment along with occlusive dressings to enhance skin effectiveness. The first patient was a 62\u2010year\u2010old woman with a history of acute myelogenous leukemia (<jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content>) who underwent allogeneic bone marrow transplantation and developed chronic <jats:styled-content style=\"fixed-case\">GVHD<\/jats:styled-content> involving 70% of her body surface area. Her <jats:styled-content style=\"fixed-case\">GVHD<\/jats:styled-content> treatment plan consisted of oral corticosteroids, oral tacrolimus, topical corticosteroids, topical tacrolimus 0.1% ointment twice\/day, emollient creams, intravenous rituximab, and photopheresis. The patient's tacrolimus trough levels rose rapidly over the course of 6\u00a0days from less than 2\u00a0ng\/ml to 23\u00a0ng\/ml, despite oral tacrolimus dosage adjustments. The second patient was a 25\u2010year\u2010old man who developed severe, chronic skin <jats:styled-content style=\"fixed-case\">GVHD<\/jats:styled-content> after undergoing allogeneic sibling bone marrow transplantation for <jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content>. In addition to intravenous corticosteroids, corticosteroid creams, and oral tacrolimus, the patient also received topical tacrolimus twice\/day with occlusive dressings. Over the course of 2\u00a0days, his tacrolimus trough levels increased from 7.10\u00a0ng\/ml to 22.10\u00a0ng\/ml. Although improvement was noted in both patients' skin <jats:styled-content style=\"fixed-case\">GVHD<\/jats:styled-content> with application of the occlusive dressings, the practice was discontinued due to increased and erratic systemic tacrolimus absorption. These case reports suggest that substantial use of topical tacrolimus with occlusive dressings in patients with cutaneous <jats:styled-content style=\"fixed-case\">GVHD<\/jats:styled-content> may contribute to increased systemic absorption resulting in toxic tacrolimus levels. Based on the findings from our two patients as well as published case reports, systemic absorption appears to increase with greater skin permeability, skin barrier dysfunction, amount of body surface area applied, and use of occlusive dressings. When one or more of these factors are present, it may be prudent to monitor tacrolimus levels.<\/jats:p>","DOI":"10.1002\/phar.1418","type":"journal-article","created":{"date-parts":[[2014,4,3]],"date-time":"2014-04-03T04:03:41Z","timestamp":1396497821000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Toxic Tacrolimus Levels After Application of Topical Tacrolimus and Use of Occlusive Dressings in Two Bone Marrow Transplant Recipients with Cutaneous Graft\u2010versus\u2010Host Disease"],"prefix":"10.1002","volume":"34","author":[{"given":"Katherine A.","family":"Olson","sequence":"first","affiliation":[{"name":"Department of Pharmacy Services State University of New York at Buffalo Buffalo New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"West","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Services Roswell Park Cancer Institute Buffalo New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip L.","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Blood and Marrow Transplant Service Roswell Park Cancer Institute Buffalo New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,4,3]]},"reference":[{"key":"e_1_2_5_2_1","unstructured":"Astellas Pharma US Inc.Protopic (tacrolimus ointment) [package insert].Deerfield IL;2009."},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.2310\/6620.2005.04045"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1705726"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.137.9.1202"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1D082"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1610-0387.2007.06455.x"},{"key":"e_1_2_5_8_1","first-page":"747","article-title":"Significant absorption of topical tacrolimus in 3 patients with Netherton syndrome","volume":"137","author":"Allen A","year":"2001","journal-title":"Arch Dermatol"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2005.02637.x"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1159\/000113941"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fphar.1418","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fphar.1418","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.1418","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:48:25Z","timestamp":1761054505000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1002\/phar.1418"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4,3]]},"references-count":9,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,6]]}},"alternative-id":["10.1002\/phar.1418"],"URL":"https:\/\/doi.org\/10.1002\/phar.1418","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4,3]]},"assertion":[{"value":"2014-04-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}