Paradoxical Severe Decrease in High-Density Lipoprotein Cholesterol Due to Rosiglitazone-Fenofibrate Interaction

ObjectiveTo determine whether the marked decrease in high-density lipoprotein cholesterol (HDL-C) occasion- ally associated with combination fibrate-thiazolidinedione therapy results from interaction between the 2 drugs or is solely the result of fibrate administration, a previously rec- ognized cause.MethodsWe prospectively followed the clinical course of 2 patients receiving fenofibrate and rosiglitazone and reviewed the relevant literature, searching PubMed for reports describing striking reductions in HDL-C associ- ated with fibrate administration alone and in conjunction with rosiglitazone and statins. Additional references were obtained from the bibliography of each identified article.ResultsEach of the 2 patients demonstrated a Drug Interaction Probability Score score of 9, indicating a highly probable likelihood of interaction. Critical review of all reported cases of concurrent fenofibrate-rosiglitazone– associated decreases in HDL-C failed to show conclusive evidence that the HDL-C decrease could be due to an inter- action between the 2 drugs as opposed to either drug being given alone.ConclusionsIn at least some patients who experience marked HDL-C decrease when given a combination of fenofibrate and rosiglitazone, this severe adverse effect is the result of a drug interaction between the 2 pharmaceuti- cal agents and is not reproduced by the administration of either drug singly. (Endocr Pract. 2010;16:382-388)