{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:43:21Z","timestamp":1761093801133,"version":"build-2065373602"},"reference-count":19,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,7,11]],"date-time":"2019-07-11T00:00:00Z","timestamp":1562803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:sec><jats:title>Study Objectives<\/jats:title><jats:p>Continuous intravenous (<jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content>) infusion bumetanide has been associated with severe myalgia in case reports, and the package labeling lists a reported incidence of 0.2% for severe myalgia. The primary objective of this study was to quantify the incidence of bumetanide infusion\u2013induced severe myalgia in patients with acute heart failure (<jats:styled-content style=\"fixed-case\">AHF<\/jats:styled-content>). Secondary objectives were to assess a dose\u2013response relationship between bumetanide infusion rate and occurrence of myalgia and to investigate potential risk factors associated with bumetanide\u2010induced myalgia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Retrospective analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Large academic medical center.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>Adults hospitalized with <jats:styled-content style=\"fixed-case\">AHF<\/jats:styled-content> who required bumetanide (\u2265\u00a00.5\u00a0mg\/hr [464 patients]) or furosemide (\u2265\u00a020\u00a0mg\/hr [197 patients]) by continuous <jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> infusion between September 2015 and May 2017.<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements and Main Results<\/jats:title><jats:p>The incidence of severe myalgia with <jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> furosemide infusion was assessed to measure confounding by indication bias. Electronic medical records were used to identify patients exposed to bumetanide 0.25\u2010mg\/ml or furosemide 2\u2010mg\/ml continuous <jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> infusions. We defined severe myalgia as a diffuse myalgia with a physician's documented suspicion of bumetanide\u2010 or furosemide\u2010induced myalgia unresponsive to electrolyte repletion and necessitating a change to alternative diuretics. The incidence of severe myalgia during bumetanide therapy was 5.8%, with the incidence increasing with higher bumetanide infusion rates: 2.6% for an infusion rate \u2264\u00a01\u00a0mg\/hour and 10.3% for a rate &gt;\u00a01\u00a0mg\/hour (p=0.0005). In the multivariate logistic regression analysis, a bumetanide infusion rate &gt;\u00a01\u00a0mg\/hour was independently associated (odds ratio 4.8, 95% confidence interval 1.94\u201312.02, p=0.0007) with severe myalgia compared to that with a rate \u2264\u00a01\u00a0mg\/hour. No patients receiving furosemide continuous <jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> infusion experienced severe myalgia, although infusion rates were lower in potency than bumetanide infusion rates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The incidence of severe myalgia in patients with <jats:styled-content style=\"fixed-case\">AHF<\/jats:styled-content> receiving bumetanide infusion was 5.8%, 29\u2010fold higher than incidence rate listed in the package labeling. Patients receiving infusion rates &gt;\u00a01\u00a0mg\/hour were 4\u2010fold more likely to experience bumetanide\u2010induced severe myalgia than those receiving rates \u2264\u00a01\u00a0mg\/hour.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.2297","type":"journal-article","created":{"date-parts":[[2019,6,21]],"date-time":"2019-06-21T10:44:30Z","timestamp":1561113870000},"page":"854-860","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Evaluation of Severe Myalgia Induced by Continuous\u2010Infusion Bumetanide in Patients with Acute Heart Failure"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0570-8505","authenticated-orcid":false,"given":"Lianjie","family":"Xiong","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences California Health Sciences University College of Pharmacy Clovis 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