warfarin and Candidiasis--Oral

Azole antimycotics and nystatin oral solution are used to treat oral candidiasis. Azoles inhibit cytochrome (CYP) P450-dependent metabolism of warfarin, which could increase the anticoagulant effect of warfarin. Nystatin is not expected to interfere with warfarin metabolism, but current data are conflicting. With this study, we aimed to explore the potential drug-drug interactions between warfarin and azole antimycotics used in the treatment of oral candidiasis, that is, systemic fluconazole, miconazole oral gel, and nystatin oral solution.. By linking clinical data on international normalized ratio (INR) measurements with administrative data on filled prescriptions of warfarin and antimycotics during 2000-2015, we explored INR changes in warfarin users relative to initiation of systemic fluconazole (n = 413), miconazole oral gel (n = 330), and nystatin oral solution (n = 399).. We found a significant increase in mean INR of 0.83 (95% confidence interval [CI] 0.61-1.04) and 1.27 (95% CI 0.94-1.59) following initiation of systemic fluconazole and miconazole oral gel, respectively. Also, the proportion of patients experiencing an INR-value above 5 was increased after initiation of fluconazole (from 4.3% to 15.3%) and miconazole (from 5.5% to 30.1%). INR was unaffected by initiation of nystatin oral solution (mean change 0.08; 95% CI -0.10 to 0.25).. Initiation of systemic fluconazole and miconazole oral gel was associated with increased INR in warfarin users. A similar association was not found for nystatin oral solution, which thus appears to be the safest alternative when treating oral candidiasis in warfarin users.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Antifungal Agents; Candidiasis, Oral; Drug Interactions; Female; Fluconazole; Gels; Humans; International Normalized Ratio; Male; Miconazole; Solutions; Warfarin

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.

Topics: Administration, Oral; Aged; Antifungal Agents; Blood Coagulation; Candidiasis, Oral; Cohort Studies; Cross-Over Studies; Drug Interactions; Female; Gels; Humans; International Normalized Ratio; Male; Miconazole; Middle Aged; Nystatin; Solutions; Warfarin

We report a case of a 76 year-old woman who had been taking warfarin for seven years because of relapsing deep venous thrombosis. Her daily maintenance dose was 5 mg. Monthly measurements of international normalised ratio (INR) were stable between 2-3. She developed oral candidiasis and miconazole gel was prescribed. One week later she developed bleeding gums. Eight days later she was admitted to the hospital with haematuria. INR was > 10. Warfarin and the miconazole gel were withdrawn. She was treated with phytonadione. INR normalised after four days and she continued warfarin treatment. Caution should be exercised whenever the combination of warfarin and miconazole gel are prescribed.

Topics: Aged; Anticoagulants; Antifungal Agents; Candidiasis, Oral; Drug Interactions; Female; Humans; Miconazole; Venous Thrombosis; Warfarin

The potentiation of the anticoagulant effects of warfarin by miconazole, when used in oral gel form, is described in three patients. The associated morbidity is examined, emphasising the importance of considering this potentially serious interaction when prescribing antifungal agents to patients on oral anticoagulants.

Topics: Administration, Oral; Aged; Anticoagulants; Antifungal Agents; Blood Coagulation; Candidiasis, Oral; Contusions; Drug Interactions; Female; Gels; Humans; Male; Melena; Miconazole; Middle Aged; Mouth Diseases; Purpura; Stomatitis, Denture; Warfarin

Topics: Administration, Oral; Administration, Topical; Aged; Anticoagulants; Antifungal Agents; Candidiasis, Oral; Contusions; Drug Interactions; Female; Hemorrhage; Humans; Miconazole; Middle Aged; Warfarin

Topics: Anti-Bacterial Agents; Anticoagulants; Antifungal Agents; Candidiasis, Oral; Drug Interactions; Erythromycin; Fluconazole; Humans; Warfarin

Oral candidosis is common, particularly in elderly patients who wear dentures. Many of these patients also have systemic diseases, including conditions for which they have to take oral anticoagulants, most commonly warfarin. Although the effect of parenterally administered miconazole on anticoagulant control is well known, the fact that small amounts of topically applied miconazole oral gel can have a similar effect is poorly recognized.

Topics: Administration, Oral; Administration, Topical; Adverse Drug Reaction Reporting Systems; Aged; Anticoagulants; Antifungal Agents; Candidiasis, Oral; Cytochrome P-450 Enzyme Inhibitors; Dental Care for Chronically Ill; Drug Synergism; Female; Gels; Humans; Miconazole; Warfarin