{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:31:21Z","timestamp":1791923481223,"version":"4.3.4"},"reference-count":22,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T00:00:00Z","timestamp":1555372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009947","name":"Merck Sharp and Dohme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009947","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Letermovir (AIC246, MK\u20108228) is a human cytomegalovirus terminase inhibitor indicated for the prophylaxis of cytomegalovirus infection and disease in allogeneic hematopoietic stem cell transplant recipients that is also being investigated for use in other transplant settings. Many transplant patients receive immunosuppressant drugs, of which several have narrow therapeutic ranges. There is a potential for the coadministration of letermovir with these agents, and any potential effect on their pharmacokinetics (PK) must be understood. Five phase 1 trials were conducted in 73 healthy female participants to evaluate the effect of letermovir on the PK of cyclosporine, tacrolimus, sirolimus, and mycophenolic acid (active metabolite of mycophenolate mofetil [MMF]), as well as the effect of cyclosporine and MMF on letermovir PK. Safety and tolerability were also assessed. Coadministration of letermovir with cyclosporine, tacrolimus, and sirolimus resulted in 1.7\u2010, 2.4\u2010, and 3.4\u2010fold increases in area under the plasma concentration\u2013time curve and 1.1\u2010, 1.6\u2010, and 2.8\u2010fold increases in maximum plasma concentration, respectively, of the immunosuppressants. Coadministration of letermovir and MMF had no meaningful effect on the PK of mycophenolic acid. Coadministration with cyclosporine increased letermovir area under the plasma concentration\u2013time curve by 2.1\u2010fold and maximum plasma concentration by 1.5\u2010fold, while coadministration with MMF did not meaningfully affect the PK of letermovir. Given the increased exposures of cyclosporine, tacrolimus, and sirolimus, frequent monitoring of concentrations should be performed during administration and at discontinuation of letermovir, with dose adjustment as needed. These data support the reduction in clinical dosage of letermovir (to 240\u00a0mg) upon coadministration with cyclosporine.<\/jats:p>","DOI":"10.1002\/jcph.1423","type":"journal-article","created":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T17:23:02Z","timestamp":1555435382000},"page":"1331-1339","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Pharmacokinetic Drug\u2010Drug Interactions Between Letermovir and the Immunosuppressants Cyclosporine, Tacrolimus, Sirolimus, and Mycophenolate Mofetil"],"prefix":"10.1002","volume":"59","author":[{"given":"Jacqueline B.","family":"McCrea","sequence":"first","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreeraj","family":"Macha","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adedayo","family":"Adedoyin","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Marshall","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Menzel","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn R.","family":"Cho","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  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