Assessment of the Association Between Colchicine Therapy and Serious Adverse Events
- 27 September 2012
- journal article
- research article
- Published by Wiley in Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
- Vol. 32 (11), 974-980
- https://doi.org/10.1002/phar.1125
Abstract
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<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.Keywords
This publication has 28 references indexed in Scilit:
- Two Cases of Acute Leukopenia Induced by Colchicine with Concurrent Immunosuppressants Use in Behçet's DiseaseYonsei Medical Journal, 2008
- Colchicine-induced toxicity in a heart transplant patient with chronic renal failureClinical Toxicology, 2008
- Rapid Onset of Muscle Weakness (Rhabdomyolysis) Associated With the Combined Use of Simvastatin and ColchicineJCR: Journal of Clinical Rheumatology, 2007
- Fatal toxic myopathy attributed to propofol, methylprednisolone, and cyclosporine after prior exposure to colchicine and simvastatinClinical Rheumatology, 2007
- Colchicine-induced rhabdomyolysisClinical Rheumatology, 2007
- Fatal Interaction between Clarithromycin and Colchicine in Patients with Renal Insufficiency: A Retrospective StudyClinical Infectious Diseases, 2005
- Cytoskeletal myotoxicity from simvastatin and colchicineMuscle & Nerve, 2004
- Guidelines for the diagnosis and management of acquired aplastic anaemiaBritish Journal of Haematology, 2003
- Colchicine induced rhabdomyolysisPublished by Oxford University Press (OUP) ,2001
- 'Arthritis' in Byzantium (AD 324-1453): unknown information from non-medical literary sources.Annals Of The Rheumatic Diseases, 1995