Drug Interactions Newsletter

Volume 1, Issue 32, 08/25/2009

Question

What is the mechanism by which the cholesterol absorption inhibitor, ezetimibe (Zetia®), increases the blood concentrations of cyclosporine (Gengraf®, Sandimmune®, Neoral®) and is it clinically relevant?

Answer

The use of the immunosuppressants, such as cyclosporine (Gengraf®, Sandimmune®, Neoral®), have led to the improvements in organ rejection related mortality.(1)  Unfortunately, a large number of organ-transplant patients will develop post-transplantation hyperlipidemia, which is caused in part by many of the immunosuppressant medications.(2-4)  A closer inspection of cyclosporine reveals that, in addition to increasing the risk for post-transplantation cardiovascular complications and contributions to drug-drug interactions, many patients are likely to require the addition of lipid lowering therapy.(4-9) 

One such lipid lowering therapy that may be given consideration is the cholesterol absorption inhibitor, ezetimibe (Zetia®).  Its candidacy for lowering low density lipoprotein cholesterol (LDL-C) in this patient population may occur as result of a perception that ezetimibe does not cause drug interactions.  Recognizing the potential for other drugs to interact with immunosuppressive therapy is important for the avoidance of adverse drug reactions, as well as preventing organ rejection.  While this perception with ezetimibe is largely true based on its pharmacokinetic profile, when coadministered with cyclosporine, it has been shown that the total exposure to cyclosporine increased by....

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