Paradoxical severe decrease in high-density lipoprotein cholesterol due to rosiglitazone-fenofibrate interaction.
OBJECTIVE
To determine whether the marked decrease in high-density lipoprotein cholesterol (HDL-C) occasionally associated with combination fibrate-thiazolidinedione therapy results from interaction between the 2 drugs or is solely the result of fibrate administration, a previously recognized cause.


METHODS
We 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 associated with fibrate administration alone and in conjunction with rosiglitazone and statins. Additional references were obtained from the bibliography of each identified article.


RESULTS
Each 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 interaction between the 2 drugs as opposed to either drug being given alone.


CONCLUSIONS
In 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 pharmaceutical agents and is not reproduced by the administration of either drug singly.
Schwing
William
W
Division of Clinical and Molecular Endocrinology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Hustak
Leighanne
L
Taylor
Harris C
HC
D000368:Aged; D008076:Cholesterol, HDL / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004347:Drug Interactions; D011345:Fenofibrate / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D011446:Prospective Studies; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000627:therapeutic use*
D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D011345:Fenofibrate