title: Miconazole and nystatin used as topical antifungal drugs interact equally strongly with warfarin.
abstract: OBJECTIVE
  Medline search disclosed 10 case reports of interactions between oral anticoagulants and miconazole oral gel, but none so far between nystatin solution and anticoagulants. We report on change in anticoagulant activity with use of different topical antifungal drugs, miconazole oral gel and vaginal suppositories, and nystatin solution.
  
  
  METHODS
  We conducted a retrospective study that included 43 patients on stable anticoagulation before the introduction of topical antifungal drugs. Miconazole oral gel was prescribed for 32 patients, nystatin solution for eight patients and miconazole vaginal suppositories for three patients.
  
  
  CONCLUSIONS
  Nineteen (44·2%) of the patients reported bleeding complications and some of these were severe. Fifteen of 32 who used miconazole oral gel and four of 8 of those who used nystatin solution were affected. Before use of the antifungal drugs, the mean weekly warfarin dose in the nystatin group was 14·5 mg, and after antifungal drugs, 9 mg, P = 0·038, while the mean international normalized ratio (INR) before antifungal drugs was 2·5 (range 1·9-3·5) and afterwards it was 10·6 (range 4·5-19·3), P = 0·0001. In the miconazole oral gel group the mean weekly warfarin dose was 15·7 mg, and after 10·8 mg, P = 0·008, while the mean INR before antifungal drugs was 2·44 (range 1·92-3·18) and afterwards it was 8·8 (range 4·9-16·9), P < 0·0001.
  
  
  CONCLUSIONS
  Miconazole oral gel and topically applied nystatin solution have equally strong effects on warfarin activity and can provoke major bleeding. Prospective evaluation of this effect is called for. However, based on our results the warfarin dose adjustment appears necessary when the anticoagulant is used concomitantly with those topical antifungals.
authors.affiliation: Haemostasis Department, Blood Transfusion Institute of Serbia, Belgrade, Serbia. mkovac008@gmail.com
authors.forename: M
authors.initials: M
authors.lastname: Kovac
authors.forename: G
authors.initials: G
authors.lastname: Mitic
authors.forename: Z
authors.initials: Z
authors.lastname: Kovac
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005782:Gels; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008825:Miconazole / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D009761:Nystatin / Q000008:administration & dosage / Q000494:pharmacology*; D012189:Retrospective Studies; D013488:Suppositories; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D000935:Antifungal Agents; D005782:Gels; D013488:Suppositories; D009761:Nystatin; D014859:Warfarin; D008825:Miconazole