title: Assessment of the association between colchicine therapy and serious adverse events.
abstract: OBJECTIVE
  As data that prompted a 2009 labeling change detailing contraindications, precautions, and dosing recommendations for the first branded colchicine product were limited to case reports of myotoxicity and blood dyscrasias ascribed to the drug, we sought to quantify the association of colchicine therapy with serious adverse outcomes in a cohort of insured patients.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Kaiser Permanente Colorado electronic data warehouses and electronic medical records.
  
  
  METHODS
  Cases were patients with a creatine kinase (CK) level of at least 2000 U/L or who developed a clinically significant non-cancer-related blood dyscrasia (thrombocytopenia, neutropenia, leukopenia, aplastic anemia, or pancytopenia) between January 1, 2006, and June 30, 2009 (954 cases). Each case was matched to up to 10 controls by age, sex, and index date (date of the increased CK level or blood dyscrasia-supporting laboratory value). Controls were patients without elevated CK levels or blood dyscrasias who had a routine health maintenance examination during the same time period (index date was the date of their health maintenance examination [9007 controls]).
  
  
  RESULTS
  The primary study outcome was colchicine exposure, defined as a colchicine prescription purchase in the 100 days before the index date. The likelihood of colchicine exposure was examined with conditional logistic regression. Cases experienced a higher rate of previous colchicine exposure compared with controls (0.6% vs 0.2%, odds ratio 3.9, 95% confidence interval 1.4-10.7). In addition, cases had higher hospitalization rates (14.9% vs 5.0%, p<0.001), higher mean chronic disease scores (2.5 vs 0.0, p<0.001), and were more likely to have been exposed to drugs that may increase the risk of adverse events due to an interaction with a CYP3A4 inhibitor drug (6.9% vs 2.3%, p<0.001).
  
  
  CONCLUSIONS
  Patients with confirmed elevations in CK level and/or blood dyscrasias had a higher rate of previous colchicine exposure, although low overall, and greater hospitalization rates and exposure to drugs that may increase the risk of adverse events compared with controls. These findings support the 2009 United States Food and Drug Administration labeling for the first branded colchicine product, cautioning use in patients with liver impairment or renal dysfunction and/or those receiving concurrent drugs that may increase risk of adverse events.
authors.affiliation: Kaiser Permanente Colorado, Aurora, Colorado 80011, USA. brittany.x.todd@kp.org
authors.forename: Brittany A
authors.initials: BA
authors.lastname: Todd
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Billups
authors.forename: Thomas
authors.initials: T
authors.lastname: Delate
authors.forename: Kara E
authors.initials: KE
authors.lastname: Canty
authors.forename: Amy B
authors.initials: AB
authors.lastname: Kauffman
authors.forename: Julia E
authors.initials: JE
authors.lastname: Rawlings
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Wagner
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology; D015331:Cohort Studies; D003078:Colchicine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D003120:Colorado / Q000453:epidemiology; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D057286:Electronic Health Records; D004791:Enzyme Inhibitors / Q000009:adverse effects; D005260:Female; D006073:Gout / Q000097:blood / Q000188:drug therapy*; D006074:Gout Suppressants / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006402:Hematologic Diseases / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D007349:Insurance, Health, Reimbursement; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000453:epidemiology; D055815:Young Adult
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D006074:Gout Suppressants; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D003078:Colchicine