Yes, Flonase (fluticasone nasal spray) can be used safely with Benadryl (diphenhydramine). There is no listed or reported interaction between the two medications.
Flonase (fluticasone) is a nasal corticosteroid indicated for the management of symptoms of allergic rhinitis and conjunctivitis. Benadryl (diphenhydramine) is a first generation, sedating antihistamine that is often used for the treatment of allergy symptoms as well as insomnia. In regard to the treatment of allergies, some studies suggest that the combined use of oral antihistamines and nasal steroids are more effective than either agent alone.
Antihistamine And Nasal Steroid Combination
While multiple studies show that nasal steroids are generally more effective for allergic rhinitis symptoms (i.e. inflammation of the nasal passages) than oral antihistamines, combined use of steroids and antihistamines have may provide more benefit than either medication alone.
One study found the combined use of Flonase and Claritin (loratadine), a second generation antihistamine, improved allergy symptoms in certain individuals more than either agent alone. These results haven't been ubiquitous however. Another study found that the combination of Nasonex (mometasone), another nasal steroid, and Claritin, was no more effective than Nasonex alone.
Nevertheless, combining a nasal steroid (such as Flonase) and an oral antihistamine (such as Benadryl) is considered safe.