title: Topical Antimycotics for Oral Candidiasis in Warfarin Users.
abstract: Treatment for oral candidiasis in warfarin users may be complicated by drug-drug interactions (DDIs) between warfarin and topically applied antimycotics. However, current knowledge of these putative DDIs is merely based on case series. We therefore performed a cohort cross-over study with the objective to evaluate the potential DDIs between warfarin and miconazole oral gel or nystatin oral solution. The cohort consisted of individuals using warfarin in the period of 1998-2012 (n ≈ 7400). We collected data on cohort members' measurements of the international normalized ratio (INR) from a clinical database, and obtained information on their use of topically applied miconazole and nystatin from a regional prescription register. Potential DDIs were assessed by comparing INR values before and after initiation of an antimycotic drug. Among 17 warfarin users exposed to miconazole oral gel, the mean INR increased from 2.5 (95% CI: 2.1-2.8) to 3.8 (95% CI: 2.8-4.8) after exposure, corresponding to a mean INR increase of 1.4 (95% CI: 0.3-2.4). Among 30 warfarin users exposed to nystatin oral solution, the mean INR was 2.7 (95% CI: 2.3-3.1) before and 2.5 (95% CI: 2.2-2.9) after exposure. In conclusion, we found evidence supporting a clinically relevant drug-drug interaction between warfarin and miconazole oral gel. In contrast, we did not find any indication of an interaction between warfarin and nystatin oral solution. Nystatin rather than miconazole should be preferred when treating warfarin users for oral candidiasis.
authors.affiliation: Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Maja
authors.initials: M
authors.lastname: Hellfritzsch
authors.affiliation: Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Anton
authors.initials: A
authors.lastname: Pottegård
authors.affiliation: Department of Clinical Chemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
authors.forename: Andreas James Thestrup
authors.initials: AJ
authors.lastname: Pedersen
authors.affiliation: Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Alaa
authors.initials: A
authors.lastname: Burghle
authors.affiliation: Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Fatima
authors.initials: F
authors.lastname: Mouaanaki
authors.affiliation: Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.|Department of Clinical Chemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Hallas
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.|Faculty of Health, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Erik Lerkevang
authors.initials: EL
authors.lastname: Grove
authors.affiliation: Department of Clinical Chemistry and Pharmacology, Odense University Hospital, Odense, Denmark.|Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Damkier
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects*; D002180:Candidiasis, Oral / Q000097:blood / Q000188:drug therapy*; D015331:Cohort Studies; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D005782:Gels; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008825:Miconazole / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D009761:Nystatin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012996:Solutions; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000935:Antifungal Agents; D005782:Gels; D012996:Solutions; D009761:Nystatin; D014859:Warfarin; D008825:Miconazole