The problem: The US Food and Drug Administration (FDA) and Health Canada have issued warnings that prothrombin times can increase for patients receiving anticoagulation therapy who also use vaginal miconazole. The warnings were posted after adverse events affected 2 patients in the US and 1 in Canada; they 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 prescription and over-the-counter formulations to counter yeast infections, have previously been documented in warfarin's product monograph. Studies have shown that minimal amounts of vaginal miconazole are absorbed systemically in healthy women of child-bearing age (Daneshmend TK. Systemic absorption of miconazole from the vagina. J Antimicrob Chemother 1986;18:507-11).
It is hypothesized that vaginal atrophy may in part be responsible for altered systemic uptake of miconazole, leading to the interaction (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]).
Health Canada and the FDA are asking manufacturers of vaginal miconazole products to add a warning to the product monograph and label informing patients who take anticoagulants that they should consult their physician before using the product.
Miconazole is marketed in Canada under several names — Miconazole, Monazole, Miconazole Nitrate Vaginal Cream, Micozole and Monistat — and in several different formulations.
What to do: The adverse interaction between these 2 drugs is uncommon, but physicians and women receiving anticoagulants should be aware of it. If miconazole is to be used vaginally, the patient's INR should be monitored and patients should be 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.
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Eric Wooltorton
CMAJ