The US Food and Drug Administration (FDA) and Health Canada have issued warnings that prothrombin times can increase for anticoagulated patients who use vaginal miconazole. The warnings were posted after adverse events for 2 patients in the US and 1 in Canada were reported to have increased INRs and associated bleeding tendencies (including bruising, gingival bleeding and nosebleeds).

The drugs

Interactions between warfarin, an anticoagulant, and systemic miconazole, used in both prescription and over-the-counter formats as yeast-infection therapy, have previously been documented in the product monograph for warfarin. Studies have shown that minimal amounts of vaginal miconazole are absorbed systemically in healthy women of child-bearing age.¹ It is hypothesized that vaginal atrophy may in part be responsible for altered systemic uptake of miconazole, leading to the interaction.²

Health Canada and the FDA are asking manufacturers of vaginal miconazole products to add a new warning to the product monograph and label informing patients taking anticoagulants that they should consult their physician before using the product.

Miconazole is marketed in Canada under the following names: Miconazole 3 Day Ovule Treatment 400 mg, Miconazole 7 Vaginal Cream 2%, Monazole 7 Cream 20 mg/g, Miconazole Nitrate Vaginal Cream, USP 2%, Micozole, Monistat 1 Vaginal Ovule, Monistat 3 Dual Pak Vag 400 Mg Ovule, Monistat 3 Vaginal Ovules 400 mg/ovule, Monistat 7 Vaginal Cream 2%, Monistat 7 Dual PAK Vaginal Suppositories 100 mg, Monistat 7 Vaginal Suppositories, Monistat 1 Combination Pack.

What to do

The warfarin-vaginal miconazole interaction is uncommon, but physicians and women receiving anticoagulants should be aware of this potential interaction. If miconazole is to be used vaginally, the patient's INR should be monitored and patients urged to report any adverse symptoms. No recommendations have yet been made regarding the concurrent use of warfarin and topical miconazole used for the treatment of skin fungi.

1.	Daneshmend TK. Systemic absorption of miconazole from the vagina. J Antimicrob Chemother 1986; 18: 507-11. [MEDLINE]
2.	Murty M. Miconazole–warfarin interaction: increased INR Can Adverse Drug React Newsl 2001;11(3):1-2. [Also in CMAJ 2001;165(1):81-2].

Copyright 2001 Canadian Medical Association or its licensors