{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T23:29:45Z","timestamp":1769124585215,"version":"3.49.0"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,10,9]],"date-time":"2019-10-09T00:00:00Z","timestamp":1570579200000},"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":[[2019,11]]},"abstract":"\n l<\/jats:sc>\n \u2010glutamine was approved by the U.S. Food and Drug Administration (\n FDA<\/jats:styled-content>\n ) for sickle cell disease (\n SCD<\/jats:styled-content>\n ) in 2017. A vaso\u2010occlusive crisis (\n VOC<\/jats:styled-content>\n ) occurs in persons with\n SCD<\/jats:styled-content>\n and is associated with acute pain episodes. This systematic review summarizes the evidence for\n l<\/jats:sc>\n \u2010glutamine in the prevention of\n VOC<\/jats:styled-content>\n and associated pain in patients with\n SCD<\/jats:styled-content>\n . Medline, Embase, and International Pharmaceutical Abstracts were searched for records reporting on\n l<\/jats:sc>\n \u2010glutamine use in persons with\n SCD<\/jats:styled-content>\n . Eligibility criteria identified primary reports of investigations conducted in humans who were administered\n l<\/jats:sc>\n \u2010glutamine, reported on outcomes related to\n VOC<\/jats:styled-content>\n or associated pain, published in English, and were available as full text. All relevant efficacy, safety, participant demographic data, and study method characteristics were extracted and documented. Risk\u2010of\u2010bias assessments were conducted using the Risk of Bias in Non\u2010Randomized Studies\u2010of Interventions (\n ROBINS<\/jats:styled-content>\n \u2010I) tool and the revised Cochrane risk\u2010of\u2010bias tool for randomized studies. Three studies assessing the effect of exogenous\n l<\/jats:sc>\n \u2010glutamine administration in patients with\n SCD<\/jats:styled-content>\n met eligibility criteria: one prospective nonrandomized controlled study and two prospective randomized controlled trials. Rate of\n VOC<\/jats:styled-content>\n and related hospitalizations were reduced in patients receiving\n l<\/jats:sc>\n \u2010glutamine, although some conflicting results were noted between studies.\n l<\/jats:sc>\n \u2010glutamine was generally well tolerated. Limitations of one or more of the eligible studies included small sample size, nonblinding, and study groups that differed at baseline.\n l<\/jats:sc>\n \u2010glutamine has limited high\u2010quality evidence supporting its use. Although\n l<\/jats:sc>\n \u2010glutamine is\n FDA<\/jats:styled-content>\n approved for the prevention of frequent episodes of\n VOC<\/jats:styled-content>\n pain, only one randomized controlled trial has strong evidence to support this indication. Based on the results of a systematic review,\n l<\/jats:sc>\n \u2010glutamine may be considered for patients unable to receive hydroxyurea or in addition to hydroxyurea for reduction in\n VOC<\/jats:styled-content>\n and associated pain.\n <\/jats:p>","DOI":"10.1002\/phar.2329","type":"journal-article","created":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T14:44:42Z","timestamp":1568126682000},"page":"1095-1104","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Systematic Review of\n l<\/scp>\n \u2010glutamine for Prevention of Vaso\u2010occlusive Pain Crisis in Patients with Sickle Cell Disease"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2861-3074","authenticated-orcid":false,"given":"Nicole E.","family":"Cieri\u2010Hutcherson","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice School of Pharmacy and Pharmaceutical Science University at Buffalo Buffalo New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1630-874X","authenticated-orcid":false,"given":"Timothy C.","family":"Hutcherson","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice D'Youville College School of Pharmacy Drug Information Center Buffalo New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin E.","family":"Conway\u2010Habes","sequence":"additional","affiliation":[{"name":"Department of Medicine Jacobs School of Medicine & Biomedical Sciences Buffalo New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brianna N.","family":"Burns","sequence":"additional","affiliation":[{"name":"D'Youville School of Pharmacy Buffalo New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan A.","family":"White","sequence":"additional","affiliation":[{"name":"D'Youville School of Pharmacy Buffalo New York"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,10,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1542\/pir.33-5-195"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcl.2013.09.006"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23232"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prrv.2013.10.005"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/JBM.S14942"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pedhc.2009.12.006"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61029-X"},{"key":"e_1_2_7_9_1","unstructured":"US Department of Health and Human Services National Institute of Health National Heart Lung and Blood Institute.Evidence\u2010Based Management of Sickle Cell Disease Expert Panel Report 2014. Available fromhttps:\/\/www.nhlbi.nih.gov\/health-topics\/evidence-based-management-sickle-cell-disease. Accessed July 2 2019."},{"key":"e_1_2_7_10_1","unstructured":"Lexi\u2010Comp Online.Hudson OH:Lexi\u2010Comp Inc. Available fromhttps:\/\/online.lexi.com. Accessed July 2 2019."},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2143(97)90062-7"},{"key":"e_1_2_7_12_1","first-page":"4","article-title":"L\u2010glutamine therapy reduces endothelial adhesion of sickle red blood cells to human umbilical vein endothelial cells","volume":"5","author":"Niihara Y","year":"2005","journal-title":"BMC Blood Disord"},{"key":"e_1_2_7_13_1","unstructured":"Endari (glutamine) [prescribing information].Torrance CA:Emmaus Medical Inc; July2017."},{"key":"e_1_2_7_14_1","unstructured":"PRISMA: Transparent Reporting of Systematic Reviews and Meta\u2010Analyses.PRISMA Statement. Available fromhttp:\/\/www.prisma-statement.org\/PRISMAStatement\/. Accessed July 2 2019."},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jebm.12141"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8652(199806)58:2<117::AID-AJH5>3.0.CO;2-V"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.4172\/2167-065X.1000116"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1715971"},{"key":"e_1_2_7_19_1","unstructured":"ClinicalTrials.gov.L\u2010Glutamine therapy for sickle cell anemia. Available fromhttps:\/\/clinicaltrials.gov\/ct2\/show\/NCT00586209. Accessed July 2 2019."},{"key":"e_1_2_7_20_1","unstructured":"ClinicalTrials.gov.L\u2010Glutamine therapy for sickle cell anemia and sickle \u03b20\u2010thalassemia. Available fromhttps:\/\/clinicaltrials.gov\/ct2\/show\/NCT00125788. 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Available fromhttps:\/\/www.novartis.com\/news\/media-releases\/novartis-announces-new-crizanlizumab-seg101-data-analysis-sickle-cell-disease-and-investment-sentry-clinical-program. Accessed July 2 2019."},{"key":"e_1_2_7_27_1","unstructured":"ClinicalTrials.gov.A study of the safety blood levels and biological effects of GBT440 in healthy subjects and subjects with sickle cell disease. Available fromhttps:\/\/clinicaltrials.gov\/ct2\/show\/NCT02285088. Accessed July 2 2019."},{"key":"e_1_2_7_28_1","unstructured":"ClinicalTrials.gov.An extension study to further evaluate the safety tolerability of GBT440 in patients with sickle cell disease who participated in the study GBT440\u2010001. Available fromhttps:\/\/clinicaltrials.gov\/ct2\/show\/NCT03041909. 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Accessed July 2 2019."}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fphar.2329","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.2329","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/phar.2329","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.2329","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T17:40:05Z","timestamp":1761068405000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1002\/phar.2329"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,9]]},"references-count":30,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,11]]}},"alternative-id":["10.1002\/phar.2329"],"URL":"https:\/\/doi.org\/10.1002\/phar.2329","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,9]]},"assertion":[{"value":"2019-10-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}