Zolmitriptan Nasal Spray Exhibits Good Long‐Term Safety and Tolerability in Migraine: Results of the INDEX Trial

Background.—Previous studies have shown that zolmitriptan 5 mg nasal spray has a fast onset of action, high efficacy, and good tolerability in the acute treatment of migraine. Objective.—This open‐label, noncomparative, multicenter, multinational phase III study was designed to further evaluate the long‐term safety and tolerability of zolmitriptan 5 mg nasal spray in a population of migraineurs largely naïve to triptan nasal sprays who treated multiple migraine attacks over a 1‐year period. Methods.—Patients were required to have an established diagnosis of migraine with or without aura (based on International Headache Society criteria), a high frequency of migraine attacks, and were allowed to treat migraine with any baseline headache intensity. A secondary objective of the study was to assess the long‐term efficacy of zolmitriptan nasal spray. A subgroup analysis aimed to determine whether rhinitis had any influence on outcomes of treatment. Results.—The safety population consisted of 538 patients who treated 20 717 migraine attacks with zolmitriptan 5 mg nasal spray. Overall, adverse events occurred in 32.8% of attacks, and led to treatment withdrawal in 4.5% of patients. The most common adverse events were unusual taste (19.0%) and paresthesia (6.8%). Adverse events were generally of mild intensity, transient, and well tolerated, showing a decline in incidence over time. Serious adverse events were rare. The presence of rhinitis and use of a second dose of trial medication had no effect on the incidence of adverse events. At 2 hours, 53.8% of attacks treated with zolmitriptan nasal spray 5 mg were rendered pain free. The highest 2‐hour pain free rates were seen for headaches of mild baseline intensity (83.3%), followed by headaches of moderate (56.5%), and severe (32.2%) baseline intensity. The 2‐hour pain‐free rate remained consistent throughout the study period. The presence of rhinitis had no effect on efficacy. Conclusions.—Zolmitriptan 5 mg nasal spray demonstrated a well‐tolerated and efficacious profile in the acute treatment of multiple migraine attacks over a 1‐year period.