Fenofibrate potentiates warfarin effects.

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Kim KY, Mancano MA

Fenofibrate potentiates warfarin effects.

Ann Pharmacother. 2003 Feb;37(2):212-5. doi: 10.1177/106002800303700210.

PubMed ID

12549950 [ View in PubMed

]

Abstract

OBJECTIVE: To describe 2 patients in whom the initiation of fenofibrate potentiated warfarin's anticoagulant effects. CASE SUMMARY: A 71-year-old white woman and an 80-year-old white woman with multiple medical conditions were both stabilized on long-term warfarin therapy. During the course of anticoagulation, both patients were prescribed fenofibrate and experienced threefold and twofold increases in international normalized ratio (INR), respectively, requiring total weekly warfarin dosage reductions of 30-40%. Before starting fenofibrate therapy, both patients' coagulation values were within the therapeutic range. When interviewed, patients and caregivers denied bleeding, bruising, changes in diet, alcohol ingestion, nonadherence with therapy, or changes in drug regimen except for the addition of fenofibrate. Upon chart review, evaluation of potentially contributory parameters, such as other changes in drug therapy, thyroid function, liver function, and drug-disease interactions, showed that these parameters remained stable and were ruled noncontributory. DISCUSSION: The addition of fenofibrate in 2 patients on stable and therapeutic doses of warfarin increased the anticoagulant response to warfarin. A clear temporal relationship with the addition of fenofibrate and the appearance of the interaction was seen. Fenofibrate is highly protein bound, with the potential to displace warfarin from its binding protein, leading to an enhanced hypoprothrombinemic effect. Fenofibrate is also a mild to moderate inhibitor of CYP2C9, the enzyme responsible for warfarin metabolism. The combination of these effects--displacement of warfarin by fenofibrate coupled with decreased metabolism of warfarin--may increase the anticoagulant response to warfarin. Using the Naranjo probability scale, these interactions were designated as probable. CONCLUSIONS: We suggest serial monitoring of INR and consider an empiric 20% reduction in warfarin dosage when fenofibrate is initiated, with the possibility for a greater warfarin dosage reduction based on INR results.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Fenofibrate	Cytochrome P450 2C9	Protein	Humans	Unknown	Inhibitor	Details

Drug Interactions

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drugs	Interaction
Integrate drug-drug interactions in your software
Acenocoumarol Etofibrate	The risk or severity of bleeding can be increased when Etofibrate is combined with Acenocoumarol.
Acenocoumarol Ciprofibrate	The risk or severity of bleeding can be increased when Ciprofibrate is combined with Acenocoumarol.
Acenocoumarol Simfibrate	The risk or severity of bleeding can be increased when Simfibrate is combined with Acenocoumarol.
Acenocoumarol Ronifibrate	The risk or severity of bleeding can be increased when Ronifibrate is combined with Acenocoumarol.
Acenocoumarol Aluminium clofibrate	The risk or severity of bleeding can be increased when Aluminium clofibrate is combined with Acenocoumarol.