{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T16:43:05Z","timestamp":1792255385891,"version":"4.4.0"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract:<\/jats:title>\n          <jats:p>Nirmatrelvir\/ritonavir (Paxlovid) consists of a peptidomimetic inhibitor (nirmatrelvir) of the SARS-CoV-2 main protease and a pharmacokinetic enhancer (ritonavir). It is approved for the treatment of mild-to-moderate COVID-19. This combination of nirmatrelvir and ritonavir can mediate significant and complex drug\u2013drug interactions (DDIs), primarily due to the ritonavir component. Indeed, ritonavir inhibits the metabolism of nirmatrelvir through cytochrome P450 3A (CYP3A) leading to higher plasma concentrations and a longer half-life of nirmatrelvir. Coadministration of nirmatrelvir\/ritonavir with immunosuppressive drugs (ISDs) is particularly challenging given the major involvement of CYP3A in the metabolism of most of these drugs and their narrow therapeutic ranges. Exposure of ISDs will be drastically increased through the potent ritonavir-mediated inhibition of CYP3A, resulting in an increased risk of adverse drug reactions. Although a decrease in the dosage of ISDs can prevent toxicity, an inappropriate dosage regimen may also result in insufficient exposure and a risk of rejection. Here, we provide some general recommendations for therapeutic drug monitoring of ISDs and dosing recommendations when coadministered with nirmatrelvir\/ritonavir. Particularly, tacrolimus should be discontinued, or patients should be given a microdose on day 1, whereas cyclosporine dosage should be reduced to 20% of the initial dosage during the antiviral treatment. Dosages of mammalian target of rapamycin inhibitors (m-TORis) should also be adjusted while dosages of mycophenolic acid and corticosteroids are expected to be less impacted.<\/jats:p>","DOI":"10.1097\/ftd.0000000000001014","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T19:09:55Z","timestamp":1660072195000},"page":"191-199","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":55,"title":["Therapeutic Drug Monitoring and Dosage Adjustments of Immunosuppressive Drugs When Combined With Nirmatrelvir\/Ritonavir in Patients With COVID-19"],"prefix":"10.1097","volume":"45","author":[{"given":"Florian","family":"Lemaitre","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Univ Rennes, CHU Rennes, Inserm, EHESP, IRSET\u2014UMR S 1085, Rennes, France;"},{"name":"INSERM, Centre d\u2019Investigation Clinique 1414, Rennes, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klemens","family":"Budde","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teun","family":"Van Gelder","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, the Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stein","family":"Bergan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Oslo University Hospital and Department of Pharmacy, University of Oslo, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Lawson","sequence":"additional","affiliation":[{"name":"University of Limoges, Inserm U1248, Pharmacology & Transplantation, Limoges, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ofelia","family":"Noceti","sequence":"additional","affiliation":[{"name":"National Center for Liver Transplantation and Liver Diseases, Army Forces Hospital, Montevideo, Uruguay;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raman","family":"Venkataramanan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy and Department of Pathology, Starzl Transplantation Institute, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Elens","sequence":"additional","affiliation":[{"name":"Integrated Pharmacometrics, Pharmacogenetic and Pharmacokinetics Research Group (PMGK), Louvain Drug for Research Institute (LDRI), Catholic University of Louvain (UCLouvain), Brussels, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk Jan A. R.","family":"Moes","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, the Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis A.","family":"Hesselink","sequence":"additional","affiliation":[{"name":"Erasmus MC Transplant Institute, University Medical Center, Rotterdam, the Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Pawinski","sequence":"additional","affiliation":[{"name":"Department of Drug Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamisha L.","family":"Johnson-Davis","sequence":"additional","affiliation":[{"name":"University of Utah Health Sciences Center and ARUP Laboratories, Salt Lake City, Utah;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda C. M.","family":"De Winter","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smita","family":"Pattanaik","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, INDIA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merc\u00e8","family":"Brunet","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Laboratory, Biochemistry and Molecular Genetics Department, Biomedical Diagnostic Center, Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, CIBERehd, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satohiro","family":"Masuda","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo 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