{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T10:12:30Z","timestamp":1789726350924,"version":"4.0.1"},"reference-count":17,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:00:00Z","timestamp":1690329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mavacamten is a potential inducer of cytochrome P450 (CYP) 3A4 and, as such, could reduce the exposure of the active components of oral contraceptives, ethinyl estradiol (EE) and norethindrone (NOR), where CYP3A4 is involved in metabolism. This study assessed if repeat doses of mavacamten led to a drug\u2013drug interaction with EE and\/or NOR. This was an open\u2010label study in healthy women. In Period 1, participants received 35\u00a0mcg of EE and 1 mg of NOR. In Period 2, participants received oral loading doses of mavacamten 25 mg on Days 1\u20132, 15 mg\/day on Days 3\u201217, and 35 mcg of EE and 1 mg of NOR on Day 15. Plasma concentrations of mavacamten, EE, and NOR were obtained before dosing and up to 72 hours after dosing. For EE only, a physiologically based pharmacokinetic model was used to simulate mavacamten\u2010mediated CYP3A4 induction with EE for various CYP2C19 phenotypes. In total, 13 women were enrolled (mean age, 38.9 [standard deviation, 9.65] years). After mavacamten administration, modest increases in area under the concentration\u2013time curves were observed for both EE and NOR. The maximum concentrations and half\u2010lives for EE and NOR were not affected by coadministration with mavacamten. Criteria for bioequivalence were met or nearly met for EE and NOR exposure with geometric mean ratios between 0.8 and 1.25. All adverse events were mild. The physiologically based pharmacokinetic model predicted a less than 15% decrease in EE exposure across CYP2C19 phenotypes. Coadministration of mavacamten at a therapeutically relevant dose with EE and NOR did not decrease the exposure to either EE or NOR to a level that may lead to reduced effectiveness.<\/jats:p>","DOI":"10.1002\/jcph.2298","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T06:23:35Z","timestamp":1687933415000},"page":"1275-1282","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Drug\u2013Drug Interaction Potential of Mavacamten with Oral Contraceptives: Results from a Clinical Pharmacokinetic Study and a Physiologically Based Pharmacokinetic Model"],"prefix":"10.1002","volume":"63","author":[{"given":"Manting","family":"Chiang","sequence":"first","affiliation":[{"name":"Bristol Myers Squibb Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Sychterz","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Gaohua","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidya","family":"Perera","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel D.","family":"Gretler","sequence":"additional","affiliation":[{"name":"Daniel Gretler Consulting San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Florea","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira","family":"Merali","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,26]]},"reference":[{"issue":"25","key":"e_1_2_10_2_1","first-page":"e558","article-title":"AHA\/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"142","author":"Ommen SR","year":"2020","journal-title":"Circulation"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4471-4956-9"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu284"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31792-X"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2018.1495856"},{"issue":"388","key":"e_1_2_10_7_1","first-page":"1","article-title":"Current contraceptive status among women aged 15\u201349: United States, 2017\u20132019","author":"Daniels K","year":"2020","journal-title":"NCHS Data Brief"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.769187"},{"key":"e_1_2_10_9_1","article-title":"Clinical drug interaction studies with combined oral contraceptives","author":"Food and Drug Administration","year":"2020","journal-title":"Services USDoHaH"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12499"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199018060-00004"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0010-7824(90)90093-B"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-0760(00)00125-4"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2008.11.008"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2007.09.025"},{"key":"e_1_2_10_16_1","unstructured":"ChiangM SychterzC PereraV PalmisanoM TempletonIE GaohuaL.PBPK\u2010informed proposed posology of mavacamten: CYP2C19 polymorphism in simulated CYP2C19 induction.Poster presented at: The 2022 American College of Clinical Pharmacology (ACCP) Annual Meeting; September 25\u201327 2022;North Bethesda MD USA."},{"key":"e_1_2_10_17_1","unstructured":"ChangP PereraV SalingerDH et\u00a0al.Population pharmacokinetics of mavacamten in adults with obstructive hypertrophic cardiomyopathy (HCM).Poster presented at: The 13th American Conference on Pharmacometrics (ACoP13); October 30\u2013November 2 2022;Aurora CO USA."},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1848"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.2298","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T07:31:14Z","timestamp":1697182274000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.2298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,26]]},"references-count":17,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1002\/jcph.2298"],"URL":"https:\/\/doi.org\/10.1002\/jcph.2298","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,26]]},"assertion":[{"value":"2023-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}