OBJECTIVES: Colchicine was originally used, and continues to be used, to treat rheumatic diseases.  It is used most frequently for the treatment of gout but is also used to treat familial Mediterranean fever, pericarditis, and Behcet’s disease. However, because of its pharmacokinetics, colchicine can interact dangerously with other drugs. The objective of the study was to analyze the association between drug-drug interactions involving colchicine and major adverse events as reported in the U.S. FDA Adverse Event Reporting System (FAERS). METHODS: All major adverse events (including death, initial or prolonged hospitalization, and persistent or significant disability) related to colchicine between 2004 and 2011 were retrieved from FAERS.  Then, events evidently caused by interactions with drugs (such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, cyclosporine, and ranolazine) were distinguished from events evidently caused by colchicine as the primary suspect drug.  Major adverse event rates were calculated.  RESULTS: Between 2004 and 2011, a total of 2655 adverse event reports involving colchicine interactions with other drugs were found in the FAERS database, of which 718 reported a death (implying a fatality ratio of 27.0%), 762 reported a hospitalization (giving a 28.7% hospitalization rate), 78 referred to life-threatening events, and 56 reported disability.  Pancytopenia, renal failure, vomiting, drug toxicity, and diarrhea were the most common reported events.  There were 4,717 reports involving colchicine as the primary suspect drug, of which 527 reported a death (fatality ratio of 11.2%).  A statistically significant (p<0.001) difference between the two fatality ratios was found.      CONCLUSIONS: When combined with certain other drugs, evidence suggests that colchicine may be associated with a relatively high death rate, especially if not dosed appropriately. In light of the current data, physicians should be keenly aware of all potentially fatal drug-drug interactions and follow therapeutic guidelines on using colchicine.