{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T09:18:14Z","timestamp":1773825494796,"version":"3.50.1"},"reference-count":13,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,5,28]],"date-time":"2014-05-28T00:00:00Z","timestamp":1401235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>In 2005, the Food and Drug Administration approved Qualaquin (quinine) for treatment of malaria and later ordered unapproved quinine formulations off the market. In 2009, labeling for Qualaquin added a warning for use for leg cramps, as serious hematologic reactions could occur. We examined quinine use trends among Medicare beneficiaries focusing on indications for use and associations with adverse hematologic outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Medicare beneficiaries, aged 65\u2009years and older, in 2006\u20132012, were included in incident quinine or comparator, diltiazem, cohorts if 183\u2009days prior to dispensing, they were enrolled in Medicare, had no dispensing of quinine, diltiazem, ticlodipine, clopidogrel, and sulfonamide drugs, and had no diagnoses of thrombocytopenia, immune thrombocytopenic purpura (ITP), thrombotic microangiopathy (TMA), or hemolytic\u2010uremic syndrome (HUS). Diagnoses of malaria or leg cramps were observed during 183\u2009days prior to index dispensing. Outcomes of ITP, TMA, or HUS in inpatient or emergency room settings were then observed during drug use.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Prevalent use of quinine decreased by 99%, from 419\u2009675 to 6036 users during 2006\u20132012. Of 88\u2009066 quinine users, 9 had diagnoses of malaria and 36\u2009218 had leg cramps. Incidence rates (per 1000 person\u2010years) for ITP were quinine 1.67 and diltiazem 0.40 [incidence rate ratio 4.2 (95% confidence interval 2.5, 6.5)], for TMA were quinine 0.23 and diltiazem 0.03 [incidence rate ratio 6.9 (95% confidence interval 1.3, 24.0)], and for HUS were quinine 0 and diltiazem 0.01.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Use of quinine decreased substantially, although diagnoses of leg cramps persist. To our knowledge, this is the first demonstration of an association for quinine and ITP and TMA in claims data. Copyright \u00a9 2014 John Wiley &amp; Sons, Ltd..<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.3644","type":"journal-article","created":{"date-parts":[[2014,5,28]],"date-time":"2014-05-28T10:46:45Z","timestamp":1401274005000},"page":"911-917","source":"Crossref","is-referenced-by-count":14,"title":["Use of an active surveillance system by the FDA to observe patterns of quinine sulfate use and adverse hematologic outcomes in CMS Medicare data"],"prefix":"10.1002","volume":"23","author":[{"given":"Monika","family":"Houstoun","sequence":"first","affiliation":[{"name":"Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research Food and Drug Administration  Silver Spring MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marsha E.","family":"Reichman","sequence":"additional","affiliation":[{"name":"Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research Food and Drug Administration  Silver Spring MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Graham","sequence":"additional","affiliation":[{"name":"Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research Food and Drug Administration  Silver Spring MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumathi","family":"Nambiar","sequence":"additional","affiliation":[{"name":"Office of New Drugs, Center for Drug Evaluation and Research Food and Drug Administration  Silver Spring MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hala","family":"Shamsuddin","sequence":"additional","affiliation":[{"name":"Office of New Drugs, Center for Drug Evaluation and Research Food and Drug Administration  Silver Spring MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. Christopher","family":"Jones","sequence":"additional","affiliation":[{"name":"Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research Food and Drug Administration  Silver Spring MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly","family":"Cao","sequence":"additional","affiliation":[{"name":"Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research Food and Drug Administration  Silver Spring MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Wernecke","sequence":"additional","affiliation":[{"name":"Acumen, LLC  Burlingame CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chelsea","family":"Lam","sequence":"additional","affiliation":[{"name":"Acumen, LLC  Burlingame CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris M.","family":"Worrall","sequence":"additional","affiliation":[{"name":"CMS\/CM  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas E.","family":"MaCurdy","sequence":"additional","affiliation":[{"name":"Stanford University  Stanford CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey A.","family":"Kelman","sequence":"additional","affiliation":[{"name":"CMS\/CM  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,5,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475\u20102875\u201010\u2010144"},{"key":"e_1_2_8_3_1","unstructured":"Centers for Disease Control and Prevention.Malaria treatment table. September2011. Available at:http:\/\/www.cdc.gov\/malaria\/resources\/pdf\/treatmenttable.pdf[1 September 2012]."},{"key":"e_1_2_8_4_1","unstructured":"Food and Drug Administration.FDA orders stop to marketing of quinine for night leg cramps. August1995. Available at:http:\/\/web.archive.org\/web\/20080115020839\/http:\/\/www.fda.gov\/fdac\/departs\/695_updates.html[22 May 2013]."},{"key":"e_1_2_8_5_1","unstructured":"ARScientific.FDA approved Qualaquin prescribing information. April2011. Available at:http:\/\/www.qualaquin.com\/q_insert.pdf[5 June 2013]."},{"key":"e_1_2_8_6_1","unstructured":"Food and Drug Administration.Questions and answers about FDA's enforcement action.2006. Available at:http:\/\/www.fda.gov\/downloads\/Drugs\/GuidanceComplianceRegulatoryInformation\/EnforcementActivitiesbyFDA\/SelectedEnforcementActionsonUnapprovedDrugs\/ucm119653.pdf[2 September 2012]."},{"key":"e_1_2_8_7_1","unstructured":"Food and Drug Administration.FDA warns of risks with unapproved use of malaria drug Qualaquin. July2010. Available at:http:\/\/www.fda.gov\/NewsEvents\/Newsroom\/PressAnnouncements\/ucm218383.htm[22 May 2013]."},{"key":"e_1_2_8_8_1","unstructured":"Food and Drug Administration.The sentinel initiative: access to electronic healthcare data for more than 25 million lives.2010. Available at:http:\/\/www.fda.gov\/downloads\/Safety\/FDAsSentinelInitiative\/UCM233360.pdf[6 June 2013]."},{"key":"e_1_2_8_9_1","unstructured":"WinkelmanJ.Nocturnal leg cramps. January2013. Available at:http:\/\/www.uptodate.com\/contents\/nocturnal\u2010leg\u2010cramps?source=search_result&search=leg+cramps&selectedTitle=1~150#H7[6 March 2013]."},{"key":"e_1_2_8_10_1","unstructured":"Centers for Disease Control and Prevention.Parasites\u2014babesiosis[online]. Available at:www.cdc.gov\/parasites\/babesiosis\/health_professionals\/index.html[28 January 2013]."},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1525-1497.1998.00182.x"},{"key":"e_1_2_8_12_1","unstructured":"The Medical Letter on Drugs and Therapeutics.In brief: safety of quinine.2010; 1350: 88."},{"key":"e_1_2_8_13_1","unstructured":"Centers for Disease Control and Prevention.About malaria[online]. Available at:http:\/\/www.cdc.gov\/malaria\/about\/[21 March 2014]."},{"issue":"9","key":"e_1_2_8_14_1","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1182\/blood.V82.9.2714.2714","article-title":"Acute thrombocytopenic purpura in relation to the use of drugs","volume":"82","author":"Kaufman DW","year":"1993","journal-title":"Blood"}],"container-title":["Pharmacoepidemiology and Drug Safety"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpds.3644","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpds.3644","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pds.3644","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T18:05:34Z","timestamp":1695492334000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pds.3644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,28]]},"references-count":13,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2014,9]]}},"alternative-id":["10.1002\/pds.3644"],"URL":"https:\/\/doi.org\/10.1002\/pds.3644","archive":["Portico"],"relation":{},"ISSN":["1053-8569","1099-1557"],"issn-type":[{"value":"1053-8569","type":"print"},{"value":"1099-1557","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,28]]}}}