{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:20:52Z","timestamp":1789791652018,"version":"4.0.1"},"reference-count":14,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>PAXLOVID (nirmatrelvir and ritonavir) and VEKLURY (remdesivir) are the first- and second-line antivirals administered to adult patients at risk of severe forms of SARS-CoV-2 infection (COVID-19), such as transplant recipients. As this specific population requires lifelong immunosuppressive treatments, the administration of antivirals with cytochrome P450-modulating properties exposes patients to a high risk of drug\u2013drug interactions (DDI).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Case Presentation:<\/jats:title>\n            <jats:p>A 72-year-old male patient who underwent a pancreatic islet transplant experienced DDI between antiviral treatment and tacrolimus during the management of SARS-CoV-2 pneumonia. The patient received a single dose of nirmatelvir\/ritonavir followed by a single dose of remdesivir. Tacrolimus treatment was interrupted for the duration of the antiviral treatment, and the concentration of tacrolimus was within the target range for this patient. Once antiviral treatment was stopped, tacrolimus was reintroduced at the initial dose. On day 6, the patient presented with clinical and biological parameters consistent with a tacrolimus overdose. A trough concentration 18 times higher than the therapeutic target was found, prompting tacrolimus to be discontinued for 9 days and reintroduced at a lower dose, followed by a gradual increase based on therapeutic drug monitoring to the initial dose. Clinical and biological parameters gradually returned to baseline levels.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Management of DDI between tacrolimus and anti-SARS-CoV-2 drugs requires a substantial therapeutic intervention and close therapeutic drug monitoring during and for several days after antiviral treatment.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/ftd.0000000000001306","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T13:00:17Z","timestamp":1738587617000},"page":"326-329","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Delayed Drug\u2013Drug Interaction Between Antiviral Drugs and Tacrolimus in a Pancreatic Islet Transplant Recipient With SARS-CoV-2 Pneumonia"],"prefix":"10.1097","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3560-0166","authenticated-orcid":false,"given":"Amelia-Naomi","family":"Sabo","sequence":"first","affiliation":[{"name":"Laboratoire de Biochimie et Biologie Mol\u00e9culaire, H\u00f4pitaux Universitaires de Strasbourg, Strasbourg, France;"},{"name":"Laboratoire de Pharmacologie et Toxicologie Neurocardiovasculaire, Unit\u00e9 de recherche 7296, Facult\u00e9 de M\u00e9decine de Ma\u00efeutique et des Sciences de la Sant\u00e9, Centre de Recherche en Biom\u00e9decine de Strasbourg (CRBS), Strasbourg, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibylle","family":"Cunat","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine Intensive et R\u00e9animation, Nouvel H\u00f4pital Civil, H\u00f4pitaux Universitaires de Strasbourg, Strasbourg, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Kemmel","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie et Biologie Mol\u00e9culaire, H\u00f4pitaux Universitaires de Strasbourg, Strasbourg, France;"},{"name":"Laboratoire de Pharmacologie et Toxicologie Neurocardiovasculaire, Unit\u00e9 de recherche 7296, Facult\u00e9 de M\u00e9decine de Ma\u00efeutique et des Sciences de la Sant\u00e9, Centre de Recherche en Biom\u00e9decine de Strasbourg (CRBS), Strasbourg, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,2,3]]},"reference":[{"key":"R1-20250509","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1056\/NEJMoa2118542","article-title":"Oral nirmatrelvir for high-risk, nonhospitalized adults with covid-19","volume":"386","author":"Hammond","year":"2022","journal-title":"N Engl J Med."},{"key":"R2-20250509","doi-asserted-by":"crossref","first-page":"e111128","DOI":"10.1371\/journal.pone.0111128","article-title":"The tacrolimus metabolism rate influences renal function after kidney transplantation","volume":"9","author":"Th\u00f6lking","year":"2014","journal-title":"PLoS One"},{"key":"R3-20250509","doi-asserted-by":"crossref","first-page":"9866","DOI":"10.3390\/ijms23179866","article-title":"The mechanism-based inactivation of CYP3A4 by ritonavir: what mechanism?","volume":"23","author":"Loos","year":"2022","journal-title":"Int J Mol Sci."},{"key":"R4-20250509","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1093\/jac\/dkaa253","article-title":"Stopping lopinavir\/ritonavir in COVID-19 patients: duration of the drug interacting effect","volume":"75","author":"Stader","year":"2020","journal-title":"J Antimicrob Chemother."},{"key":"R5-20250509","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1002\/cpt.2646","article-title":"Recommendations for the management of drug-drug interactions between the COVID-19 antiviral nirmatrelvir\/ritonavir (paxlovid) and comedications","volume":"112","author":"Marzolini","year":"2022","journal-title":"Clin Pharmacol Ther."},{"key":"R6-20250509","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1111\/ajt.13111","article-title":"Pharmacokinetics and dose recommendations for cyclosporine and tacrolimus when coadministered with ABT-450, ombitasvir, and dasabuvir","volume":"15","author":"Badri","year":"2015","journal-title":"Am J Transpl."},{"key":"R7-20250509","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.therap.2022.03.005","article-title":"Management of drug-drug interactions with nirmatrelvir\/ritonavir in patients treated for Covid-19: guidelines from the French Society of Pharmacology and Therapeutics (SFPT)","volume":"77","author":"Lemaitre","year":"2022","journal-title":"Therapie"},{"key":"R8-20250509","doi-asserted-by":"crossref","first-page":"655","DOI":"10.3390\/ph14070655","article-title":"ADME and pharmacokinetic properties of remdesivir: its drug interaction potential","volume":"14","author":"Deb","year":"2021","journal-title":"Pharmaceuticals"},{"key":"R9-20250509","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1111\/cts.12815","article-title":"What do we know about remdesivir drug interactions?","volume":"13","author":"Yang","year":"2020","journal-title":"Clin Transl Sci."},{"key":"R10-20250509","doi-asserted-by":"crossref","first-page":"765","DOI":"10.3390\/ph17060765","article-title":"Efficacy and safety of remdesivir in adult solid organ transplant recipients: a scoping review","volume":"17","author":"Smith","year":"2024","journal-title":"Pharmaceuticals"},{"key":"R11-20250509","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1016\/j.ekir.2023.04.028","article-title":"Potential effects of remdesivir on tacrolimus exposure in transplant recipients with COVID-19 infection","volume":"8","author":"Habeeb","year":"2023","journal-title":"Kidney Int Rep"},{"key":"R12-20250509","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s13181-022-00922-2","article-title":"Tacrolimus drug\u2013drug interaction with nirmatrelvir\/ritonavir (PaxlovidTM) managed with phenytoin","volume":"19","author":"Sindelar","year":"2023","journal-title":"J Med Toxicol."},{"key":"R13-20250509","doi-asserted-by":"crossref","first-page":"218.e5","DOI":"10.1016\/j.ajem.2023.04.045","article-title":"Tacrolimus toxicity due to enzyme inhibition from ritonavir","volume":"69","author":"Snee","year":"2023","journal-title":"Am J Emerg Med."},{"key":"R14-20250509","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00467-018-4117-x","article-title":"The potential impact of hematocrit correction on evaluation of tacrolimus target exposure in pediatric kidney transplant patients","volume":"34","author":"Schijvens","year":"2019","journal-title":"Pediatr Nephrol (Berlin, Germany)"}],"container-title":["Therapeutic Drug 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