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Mast Cell Activation Syndrome Treatment Conventional treatment for mast cell activation syndrome generally involves the use of pharmaceutical and over-the-counter medications to alleviate symptoms, such as the following medications: Epinephrine (such as an EpiPen) for severe reactions First generation H1 blockers diphenhydramine (Benadryl) and hydroxyzine (Vistaril) Second generation H1 blockers, including loratadine (Claritin), cetirizine (Zyrtec), and fexofenadine (Allegra) H2 blockers, such as ranitidine (Zantac) and famotidine (Pepcid) Aspirin, to block production of prostaglandin D2 and reduce flushing