#Nystatin swish series

#Nystatin swish series

Despite this lack of biological plausibility for DDIs, a recent case series reported substantially increased INR values and bleedings in patients using warfarin and nystatin concomitantly, leading to speculations on the safety of nystatin in this setting 16. Furthermore, nystatin does not inhibit the CYP450 system 15, and DDIs involving nystatin have not been conclusively confirmed. On the other hand, gastrointestinal absorption of nystatin is negligible when taken as an oral solution 14. Increased values of international normalized ratio (INR) and bleedings after concomitant treatment with warfarin have been described in case reports 11, 12 and in a small case series of six patients 13. Gastrointestinal absorption of miconazole occurs to some extent when administered as an oral gel 10. Miconazole is a strong inhibitor of CYP2C9 9. The potential for the development of treatment resistance is considered lower for nystatin compared to treatment with azoles, including miconazole 8. The effectiveness of nystatin and miconazole against oral candida infections is considered comparable 7. In Denmark, only miconazole and nystatin are marketed for this indication. greater potential for DDIs and development of treatment-resistant fungal strains), topically applied clotrimazole, miconazole or nystatin is generally recommended internationally as the first-line choice of treatment for oral candidiasis 6. Due to disadvantages of systemic antimycotic therapy (e.g. Many warfarin users are elderly persons with a high frequency of comorbid conditions and concomitant medications 5 who are at increased risk of developing local fungal infections, primarily oral candidiasis 6. Warfarin has a narrow therapeutic index, and even minor DDIs may therefore have serious consequences 4. As warfarin is metabolized by the cytochrome P450 system (CYP), especially CYP2C9 3, warfarin users are susceptible to drug–drug interactions (DDIs). Warfarin is widely used in the prophylaxis and treatment of thrombosis 1, 2. Nystatin rather than miconazole should be preferred when treating warfarin users for oral candidiasis. In contrast, we did not find any indication of an interaction between warfarin and nystatin oral solution. In conclusion, we found evidence supporting a clinically relevant drug–drug interaction between warfarin and miconazole oral gel. 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.

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).

Potential DDIs were assessed by comparing INR values before and after initiation of an antimycotic drug. 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. The cohort consisted of individuals using warfarin in the period of 1998–2012 (n ≈ 7400). 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. However, current knowledge of these putative DDIs is merely based on case series. Treatment for oral candidiasis in warfarin users may be complicated by drug–drug interactions (DDIs) between warfarin and topically applied antimycotics.