BACKGROUND: Therapeutic options for pain management are restricted in patients with nonsteroidal anti-inflammatory drug (NSAID)-induced or NSAID-exacerbated urticaria because strong cyclooxygenase (COX)-I inhibiting NSAID cannot be used. Alternative NSAID such as weak COX-I inhibitors or selective COX-II inhibitors are sometimes not sufficiently effective or have potentially troublesome adverse effects. OBJECTIVE: To date, prophylactic premedication with H-1-antihistamines is rarely practiced in patients concurrently suffering from recurrent pain and NSAID-associated urticaria. Our data analysis aims to clarify whether prophylactic premedication before the intake of NSAID is effective, safe, and practicable. METHODS: Data of 21 patients with NSAID-induced or NSAID-exacerbated urticaria who underwent single dose NSAID provocation 30 minutes after premedication with 5 mg desloratadine were retrospectively evaluated. RESULTS: After H-1-antihistamine premedication, 17 patients tolerated 16 single dose provocation tests with strong COX-I inhibitors and 2 tests with weak COX-I inhibitors. Despite H1-antihistamine premedication, 2 patients developed acute urticaria after intake of 400 mg ibuprofen. Another 2 patients with acute urticaria after intake of 800 mg ibuprofen tolerated 400 mg ibuprofen and 1000 mg paracetamol, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In the majority of patients with NSAID-induced or NSAID-exacerbated urticaria concurrently suffering from intermittent pain, a premedication regimen with 5 mg desloratadine 30 minutes before intake of a strong COX-I inhibitor seems to be effective, safe, and practicable. (C) 2016 American Academy of Allergy, Asthma & Immunology