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 naive 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.