Warfarin Institute of America
DEDICATED TO YOUR HEALTH SINCE 2000
Aprepitant Interaction with Warfarin
Brand Name: Emend
Aprepitant is metabolized by the liver enzyme known as CYP450-3A4. One form of warfarin is also metabolized by this enzyme. However, the effect of this enzyme on the International Normalized Ratio (INR) is usually insignificant.
Warfarin is found in two forms that are mirror images of each other (think right and left hands). For warfarin to work, it has to fit on a receptor site (think of a hand going into a glove). Almost all of the warfarin in a tablet is the left-handed form. Almost all of the receptors in the body are like gloves for the left hand. The 3A4 enzyme only is responsible for the metabolism of the right-handed form. Since the right handed form makes up very little of each tablet and there are few right-handed receptors anything that affects the right-handed form has only a negligible effect on the INR.
For some unknown reason, the US Food and Drug Administration fails to understand this. They require a statement in the package insert that goes with each container of aprepitant to advise that careful monitoring of the INR is necessary when it is started or stopped for someone taking warfarin.
There is a reason for monitoring warfarin carefully for anyone who has nausea and vomiting but it is not related to the 3A4 enzyme. People who have nausea and/or vomiting are very unlikely to be eating their normal diet. When a person does not eat normally, their INR is almost always high.
My method is to monitor people on chemotherapy approximately every two weeks. They are by definition unstable because of the effects of the chemotherapy. By monitoring them frequently, many of the bleeding or clotting episodes that they are likely to experience can be avoided.
Reference:
Emend Package Insert. June 2006. Merck and Co., INC. Whitehouse Station NJ, USA.
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Last updated June 14, 2007
