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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Medicare beneficiaries, aged 65 years and older, in 2006-2012, were included in incident quinine or comparator, diltiazem, cohorts if 183 days 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-uremic syndrome (HUS). Diagnoses of malaria or leg cramps were observed during 183 days prior to index dispensing. Outcomes of ITP, TMA, or HUS in inpatient or emergency room settings were then observed during drug use.
  
  
  RESULTS
  Prevalent use of quinine decreased by 99%, from 419 675 to 6036 users during 2006-2012. Of 88 066 quinine users, 9 had diagnoses of malaria and 36 218 had leg cramps. Incidence rates (per 1000 person-years) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Monika
authors.initials: M
authors.lastname: Houstoun
authors.forename: Marsha E
authors.initials: ME
authors.lastname: Reichman
authors.forename: David J
authors.initials: DJ
authors.lastname: Graham
authors.forename: Sumathi
authors.initials: S
authors.lastname: Nambiar
authors.forename: Hala
authors.initials: H
authors.lastname: Shamsuddin
authors.forename: S Christopher
authors.initials: SC
authors.lastname: Jones
authors.forename: Kelly
authors.initials: K
authors.lastname: Cao
authors.forename: Michael
authors.initials: M
authors.lastname: Wernecke
authors.forename: Chelsea
authors.initials: C
authors.lastname: Lam
authors.forename: Chris M
authors.initials: CM
authors.lastname: Worrall
authors.forename: Thomas E
authors.initials: TE
authors.lastname: MaCurdy
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kelman
mesh_terms: D000368:Aged; D014487:Centers for Medicare and Medicaid Services, U.S.; D016208:Databases, Factual; D004110:Diltiazem / Q000009:adverse effects / Q000627:therapeutic use; D017277:Drug Approval; D004348:Drug Labeling; D006801:Humans; D015994:Incidence; D008288:Malaria / Q000188:drug therapy*; D006278:Medicare; D009120:Muscle Cramp / Q000188:drug therapy*; D009125:Muscle Relaxants, Central / Q000009:adverse effects / Q000627:therapeutic use*; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000453:epidemiology; D011803:Quinine / Q000009:adverse effects / Q000627:therapeutic use*; D057049:Thrombotic Microangiopathies / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration
chemical_list: D009125:Muscle Relaxants, Central; D011803:Quinine; D004110:Diltiazem
keywords: active surveillance; hematologic; pharmacoepidemiology; quinine