OBJECT DRUGS

Anticoagulants, Oral:

• Acenocoumarol
• Warfarin (Coumadin, etc.)

PRECIPITANT DRUGS

Enzyme Inhibitors:

• Amiodarone (Cordarone, etc.)
• Androgens
• Capecitabine (Xeloda)
• Ceritinib (Zykadia)
• Danazol (Danocrine)
• Disulfiram (Antabuse)
• Etravirine (Intelence)
• Fenofibrate (Tricor, etc.)
• Fluorouracil (5-FU)
• Gemfibrozil (Lopid)
• Imatinib (Gleevec)
• Leflunomide (Arava)
• Lomitapide (Juxtapid)
• Mefloquine (Lariam)
• Tamoxifen (Nolvadex)
• Valproic Acid (Depakote, etc.)
• Zafirlukast (Accolate)

Comment:

CYP2C9 inhibitors increase S-warfarin concentrations; the increased anticoagulant effect is usually gradual (over 7-10 days). The interaction magnitude varies considerably from patient to patient, and is usually dose related. Amiodarone may also increase oral anticoagulant response by increasing circulating thyroid hormone concentrations. The mechanism for the effect of androgens, danazol, and fibrates (clofibrate, fenofibrate, gemfibrozil) on warfarin response is not established. The leflunomide-warfarin interaction is based on limited clinical information. Most studies involve warfarin, but assume that acenocoumarol interacts similarly until proved otherwise. Phenprocoumon is primarily glucuronidated; it is unlikely to interact with CYP2C9 inhibitors.

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative:
• Zafirlukast: Montelukast (Singulair) does not appear to interact with warfarin. Zileuton (Zyflo) may increase warfarin response somewhat, but probably to a lesser extent than zafirlukast.
• Monitor: If a CYP2C9 inhibitor is used, monitor for altered anticoagulant effect if inhibitor is initiated, discontinued, or changed in dosage. Amiodarone-induced inhibition may require several weeks to develop.