{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:21:02Z","timestamp":1789791662664,"version":"4.0.1"},"reference-count":9,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Transplantation"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Paxlovid, a fixed combination nirmatrelvir and ritonavir (NIM\u2010RTV), is a potent inhibitor of cytochrome P450 3A4 (CYP3A4) isoenzyme. It is approved for the treatment of mild to moderate COVID\u201019 infections in patients at risk for serious infection. The metabolism of tacrolimus, a CYP3A4 substrate, is significantly reduced in those receiving NIM\u2010RTV. Coadministration of NIM\u2010RTV without tacrolimus dose reduction may result in toxicity. CYP3A4\u2010inducing medications, including phenytoin, fosphenytoin or rifampin, may reverse toxicity while achieving rapid clearance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case Presentation<\/jats:title><jats:p>A 14\u2010year\u2010old, 66.5\u2009kg African American female with a history of chronic kidney disease stage 5 secondary to collapsing focal segmental glomerulosclerosis (FSGS) underwent an uncomplicated deceased donor kidney transplant at 12\u2009years of age. Approximately 2.5\u2009years after transplant, she tested positive for COVID\u201019. NIM\u2010RTV was prescribed through a local pharmacy. She presented 3.5\u2009days later with nausea, vomiting, fatigue, and oligo\u2010anuria with acute kidney injury (AKI) and creatinine of 2.6\u2009mg\/dL from baseline of 0.7\u2009mg\/dL. Tacrolimus level was &gt;\u200960\u2009ng\/mL. Phenytoin\/fosphenytoin was initiated to induce tacrolimus clearance due to sustained AKI and neurological risk. Within 36\u2009h, her tacrolimus level was 38\u2009ng\/mLwith improved urine output. After 3\u2009days, her tacrolimus level 11.9\u2009ng\/mL and serum creatinine was near baseline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>To our knowledge, this is the first report of a pediatric kidney transplant patient with tacrolimus toxicity secondary to NIM\u2010RTV therapy utilizing phenytoin\/fosphenytoin to induce tacrolimus metabolism and prevent further toxicity. Heightened awareness of this interaction is paramount to reduce allograft injury and promote patient safety.<\/jats:p><\/jats:sec>","DOI":"10.1111\/petr.70030","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T03:28:39Z","timestamp":1742959719000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Case Report of Successful Use of Phenytoin\/Fosphenytoin in a Pediatric Kidney Transplant Recipient With Nirmatrelvir\/Ritonavir\u2010Induced Tacrolimus Allograft Injury"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8418-0741","authenticated-orcid":false,"given":"Jennifer L.","family":"Hewlett","sequence":"first","affiliation":[{"name":"Department of Pharmacy Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selasie","family":"Goka","sequence":"additional","affiliation":[{"name":"Division of Nephrology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uche","family":"Nwaogazie","sequence":"additional","affiliation":[{"name":"Division of Nephrology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Finkel","sequence":"additional","affiliation":[{"name":"Division of Nephrology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Galea","sequence":"additional","affiliation":[{"name":"Division of Nephrology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonya","family":"Lopez","sequence":"additional","affiliation":[{"name":"Division of Nephrology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Laskin","sequence":"additional","affiliation":[{"name":"Division of Nephrology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"LaRosa","sequence":"additional","affiliation":[{"name":"Division of Nephrology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5015-8146","authenticated-orcid":false,"given":"Kevin J.","family":"Downes","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7357-242X","authenticated-orcid":false,"given":"Sandra","family":"Amaral","sequence":"additional","affiliation":[{"name":"Division of Nephrology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Biostatistics, Epidemiology and Informatics University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Savant","sequence":"additional","affiliation":[{"name":"Division of Nephrology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5566-0768","authenticated-orcid":false,"given":"Bernarda","family":"Viteri","sequence":"additional","affiliation":[{"name":"Division of Nephrology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"PAXLOVID (Nirmatrelvir Tablets; 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