Warfarin Institute of America
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FENOFIBRATE INTERACTIONS WITH WARFARIN
Ascah et al report an interaction between warfarin and fenofibrate. A 79 year-old man who was started on fenofibrate 67 mg three times daily. One month later, the man experienced fainting and blood in his stools. His INR was found to be 18. His treatment required 4 units of packed red blood cells and 1 unit of fresh frozen plasma. He was hospitalized for 5 days. The fenofibrate was discontinued and simvastatin started. The same warfarin dose that the patient was taking before the incident again maintained his INR in the desired range.
Editor's Note: I think that this case has two lessons. First, it was probably not a good idea to start the patient on the maximum fenofibrate dose. The prescribing information clearly states that, "In the elderly, the initial dose should ... be limited to 67 mg per day." A 79 year-old man taking six medications daily would qualify as elderly. Second, there were reports in the medical literature of an interaction occurring between these two drugs. It would have been prudent to have scheduled his INR to be monitored in one to two weeks since the previous reports stated that the interaction was apparent after 5 to 10 days.
Aldridge et al report two cases where patient's INRs increased when fenofibrate was added to their medications, including warfarin. They performed several tests to confirm that this was indeed a true drug interaction. These tests were positive.
The authors report that the interaction is evident at five to ten days after fenofibrate is started. They recommend monitoring the INR three times per week until the warfarin dose is again stabilized.
Editor's Note: I do not usually recommend monitoring the INR three times per week. This is one of the major reasons for INRs being out of range. When the INR is monitored three times per week frequent changes of the warfarin dose are made. As a result, the INR does not have time to stabilize. In my experience, it is unlikely that the INR will go far enough out of range to cause a serious reaction if the INR is monitored weekly.
Kim and Mancano report the cases of two women (71 and 80 years of age) who had fenofibrate added to their warfarin therapy. They required 30 to 40% reductions in their warfarin dosages to bring the INR back into the therapeutic range. After other factors were ruled-out, this was declared a probably drug interaction. The authors suggest reducing the warfarin dose by 20% when fenofibrate is added to warfarin.
I could find no report of the effect of discontinuing fenofibrate when patients were taking both it and warfarin. However, it seems prudent to monitor the INR frequently when fenofibrate is stopped and warfarin continued.
Holbrook et al. published a systematic review of warfarin and its interactions. They rate this as an interaction that is highly probable for raising the INR, necessitating a lower warfarin dose when fenofibrate is added to the medications of someone already taking warfarin.
References:
Ascah KJ et al. Interaction between fenofibrate and warfarin. Ann Pharmacother 1998;32:765-768.
Aldridge MA et al. Fenofibrate and Warfarin Interaction. Pharmacotherapy 2001;21:886-889.
Kim KY, Mancano MA. Fenofibrate Potentiates Warfarin Effects. Ann Pharmacother 2003;37:212-215.
Holbrook AM et al. Systematic Overview of warfarin and its drug and food interactions. Arch Intern Med 2005;165:1096-1106.
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Last updated May 25, 2005