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Assessment of the Association Between Colchicine Therapy and Serious Adverse Events
Author(s) -
Todd Brittany A.,
Billups Sarah J.,
Delate Thomas,
Canty Kara E.,
Kauffman Amy B.,
Rawlings Julia E.,
Wagner Theresa M.
Publication year - 2012
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.1125
Subject(s) - medicine , dyscrasia , leukopenia , adverse effect , neutropenia , odds ratio , confidence interval , surgery , chemotherapy , bone marrow , plasma cell
Study 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. Design Case‐control study. Data Source Kaiser Permanente Colorado electronic data warehouses and electronic medical records. Patients 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 J anuary 1, 2006, and J une 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]). Measurements and Main 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 r atio 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). Conclusion 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.