Assessment of the Association Between Colchicine Therapy and Serious Adverse Events

• Published in: Pharmacotherapy 2012-11, Vol.32 (11), p.974-980
• Main Authors: Todd, Brittany A., Billups, Sarah J., Delate, Thomas, Canty, Kara E., Kauffman, Amy B., Rawlings, Julia E., Wagner, Theresa M.
• Format: Article
• Language: English
• Subjects: Adult; Aged; aplastic anemia; Biological and medical sciences; blood dyscrasia; Case-Control Studies; Chemical and Drug Induced Liver Injury - epidemiology; Cohort Studies; colchicine; Colchicine - administration & dosage; Colchicine - adverse effects; Colchicine - therapeutic use; Colorado - epidemiology; creatine kinase; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Drug toxicity and drugs side effects treatment; Electronic Health Records; Enzyme Inhibitors - adverse effects; Female; Gout - blood; Gout - drug therapy; Gout Suppressants - administration & dosage; Gout Suppressants - adverse effects; Gout Suppressants - therapeutic use; Hematologic Diseases - chemically induced; Hematologic Diseases - epidemiology; Humans; Insurance, Health, Reimbursement; leukopenia; Male; Medical sciences; Middle Aged; myotoxicity; neutropenia; Pharmacology. Drug treatments; Prevalence; Renal Insufficiency - chemically induced; Renal Insufficiency - epidemiology; rhabdomyolysis; thrombocytopenia; Toxicity: blood; Young Adult
• ISSN: 0277-0008; 1875-9114
• DOI: 10.1002/phar.1125

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 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]). 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 ratio 3.9, 95% confidence interval 1.4–10.7). In addition, cases had higher hospitalization rates (14.9% vs 5.0%, p