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However, as a lipophilic weak base, crystalline monohydrate, dasatinib (Sprycel\u00ae) is poorly soluble, rendering a pH\u2010dependent absorption and a highly variable bioavailability. Thus, co\u2010medication with proton pump inhibitors (PPI) profoundly impairs dasatinib uptake and is clearly recommended against.<\/jats:p><jats:p>XS004 is a novel oral immediate release and amorphous solid dispersion (ASD) formulation of dasatinib and is bioequivalent to the original crystalline dasatinib at 30% lower dosages. XS004 is designed to mitigate gastric pH dependency, thus optimizing absorption and bioavailability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the prevalence of dasatinib and PPI co\u2010medication among chronic\u2010phase CML patients in a real\u2010world setting and assessed the plasma pharmacokinetics (PK) of XS004 with and without PPI co\u2010medication (omeprazole) in healthy volunteers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using the Swedish CML and Prescribed Drug Registers, we identified 676 TKI\u2010treated CML patients; 320 (47%) had been prescribed PPI at some point after CML diagnosis. Among dasatinib\u2010treated patients, the 2\u2010year cumulative PPI co\u2010medication was 24%. Interestingly, the 5\u2010year overall survival was significantly lower for TKI\u2010treated CML patients with versus without PPI co\u2010medication (79% vs. 94%; hazard ratio 3.5; 95% confidence interval, 2.1\u20135.3; <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001).<\/jats:p><jats:p>When assessing PK of XS004, neither <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> nor area under the plasma concentration curve levels in plasma were significantly altered by the PPI co\u2010medication.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In conclusion, despite warnings, PPI co\u2010medication is common among dasatinib\u2010treated CML patients in a real\u2010world setting. The new XS004 ASD formulation of dasatinib provided, in contrast to original crystalline dasatinib, superior pH independence with stable bioavailability, thereby minimizing drug\u2013drug interactions. This may improve the long\u2010term efficacy and tolerability of dasatinib in CML.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.14059","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T10:10:25Z","timestamp":1690539025000},"page":"644-654","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Despite warnings, co\u2010medication with proton pump inhibitors and dasatinib is common in chronic myeloid leukemia, but <scp>XS004<\/scp>, a novel oral dasatinib formulation, provides reduced <scp>pH\u2010dependence<\/scp>, minimizing undesirable <scp>drug\u2013drug<\/scp> interactions"],"prefix":"10.1111","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1549-8695","authenticated-orcid":false,"given":"Gunnar","family":"Larfors","sequence":"first","affiliation":[{"name":"Unit of Hematology, Department of Medical Sciences Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Andersson","sequence":"additional","affiliation":[{"name":"Xspray  Solna Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9rald","family":"Jesson","sequence":"additional","affiliation":[{"name":"Xspray  Solna Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotta","family":"Liljebris","sequence":"additional","affiliation":[{"name":"Xspray  Solna Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Brisander","sequence":"additional","affiliation":[{"name":"Xspray  Solna Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Lennern\u00e4s","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Translational Drug Discovery and Development Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif","family":"Stenke","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital and Karolinska Institutet, Department of Hematology Theme Cancer and Department of Medicine Solna  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12743"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.892684"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.2335"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.73"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10010077"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2015.05.013"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1016212804288"},{"key":"e_1_2_11_9_1","unstructured":"European Medicines Agency.Sprycel: EPAR\u2014Scientific Discussion.2006. 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