Open-label, long-term tolerability of naratriptan for short-term prevention of menstrually related migraine

Background.-Although naratriptan is not approved for prophylactic use in migraine, naratriptan has been shown to be significantly more effective than placebo for short-term prevention of menstrually related migraine (MRM). The tolerability of naratriptan administered intermittently for prophylaxis for MRM over the long term has not been assessed. Objective.-To assess the tolerability of naratriptan 1 mg given twice daily for 6 days per month, administered for up to 1 year for short-term prevention of MRM in an open-label study. Methods.-Patients were eligible for the study if they were between 18 and 65 years of age and had at least a 1-year history of migraine, with or without aura, as defined by 1988 International Headache Society criteria; reported a history of MRM; and had at least 1 MRM attack during their last menstrual cycle. MRM was defined as any migraine beginning during the perimenstruall period (PMP). By definition, the PMP consisted of Days -2, -1,1,2,3, and 4, with Day 1 being the first day of menstrual flow. During each menstrual cycle occurring over a 1-year period, patients began short-term treatment with naratriptan 1 mg twice daily (BID) 3 days before the expected onset of MRM and treated for a total of 6 days. Naratriptan 2.5 mg could be taken for breakthrough MRM attacks. Tolerability and safety measures included adverse events, standard clinical laboratory tests, electrocardiograms (ECGs), and vital signs. The secondary endpoints were the percentage of PMPs without MRM; headache disability as measured by the Headache Impact Test (HIT), and psychological health as measured by the Beck Depression Inventory version 2 (BDI-II). Results.-The number of patients who took at least 1 dose of study medication (safety population) was 457, and the numbers of patients completing 6 months and 12 months of treatment were 318 and 131, respectively. Note that 171 (37%) patients were asked to leave the study once target enrollment numbers were met. The only adverse event occurring at an incidence of more than 2% during the 6-day treatment periods when naratriptan 1 mg BID was taken with or without an additional 2.5-mg dose for breakthrough attacks was ear, nose, throat infection (3%). No specific adverse event considered at least possibly to be related to study medication occurred in more than 2% of patients. No serious drug-related adverse events were reported. Furthermore, no patient experienced clinically relevant drug-related changes in 12-lead ECGs, vital signs, or clinical laboratory tests. Patients in both the 6- and 12-month populations did not experience an MRM in approximately 50% of treated PMPs. Health outcomes results suggested that naratriptan reduced headache impact when used for up to 12 months for the short-term prevention of MRM. Conclusion.-Naratriptan 1 mg BID, with the optional use of an additional 2.5-mg dose for breakthrough attacks, was well tolerated when used for 6 continuous days per month for up to 1 year for short-term prevention of MRM.