Methotrexate for topical application in an extemporaneous preparation

Background: The antifolate agent methotrexate is routinely used for systemic therapy of cancer and chronic inflammatory diseases. Successful topical use has been described for individual therapeutic attempts, in case series, and small studies, especially for mycosis fungoides (premycotic stage) and lymphomatoid papulosis. With respect to its clinical use in selected treatment scenarios, there have been no approved preparations or regulated instructions for pharmaceutical compounding. Material and methods: Two high performance liquid chromatography methods were established for the determination of the active substance within a galenic formulation as well as within extracts of biological material. Suitable vehicles for epicutaneous application were developed and preclinically tested for stability, release, and pharmacokinetics of the active substance as well as their safety. Results: The tests show that methotrexate may be readily incorporated into "Basiscreme DAC". It remains stable up to a concentration of 0.5 %. This preparation releases enough active substance to achieve relevant local bioavailability in the respective target compartments of the skin. There is no evidence of safety risks due to relevant systemic bioavailability after topical application on a limited area of the skin. Conclusions: In summary, this approved prescription for extemporaneous preparation complies with the requirements of the German Ordinance on the Operation of Pharmacies (Article 7 ApBetrO), and the available data proves its stability and pharmaceutical quality.