title: Safety and tolerability of frovatriptan in the acute treatment of migraine and prevention of menstrual migraine: Results of a new analysis of data from five previously published studies.
abstract: BACKGROUND
  Triptans are a recommended first-line treatment for moderate to severe migraine.
  
  
  OBJECTIVE
  Using clinical trial data, we evaluated the safety and tolerability of frovatriptan as acute treatment (AT) and as short-term preventive (STP) therapy for menstrual migraine (MM).
  
  
  METHODS
  Data from 2 Phase III AT trials (AT1: randomized, placebo controlled, 1 attack; AT2: 12-months, noncomparative, open label) and 3 Phase IIIb STP trials in MM (MMP1 and MMP2: randomized, placebo controlled, double blind, 3 perimenstrual periods; MMP3: open label, noncomparative, 12 perimenstrual periods) were analyzed. In AT1, patients treated each attack with frovatriptan 2.5 mg, sumatriptan 100 mg, or placebo. In AT2, they used frovatriptan 2.5 mg. In MMP1 and MMP2, women administered frovatriptan 2.5 mg for 6 days during the perimenstrual period, taking a loading dose of 2 or 4 tablets on day 1, followed by once-daily or BID frovatriptan 2.5 mg, respectively; in MMP3, they used BID frovatriptan 2.5 mg. In AT1, which was previously published in part, group differences in adverse events (AEs) were analyzed using the Fisher exact test, and response rates were compared using logistic regression. Post hoc analyses of sustained pain-free status with no AEs (SNAE) and sustained pain response with no AEs (SPRNAE) were performed using a 2-sample test for equality of proportions without continuity correction. For AT2 and the STP studies, data were summarized using descriptive statistics. Results of individual safety analyses for the STP studies were previously reported; the present report includes new results from a pooled analysis of MMP1 and MMP2 and a new analysis of MMP3 in which AEs were coded using Medical Dictionary for Regulatory Activities version 8.0.
  
  
  RESULTS
  AT1 included 1206 patients in the safety group; AT2 included 496. In the STP studies, safety data were collected for 1487 women. In AT1 and AT2, 85.6% and 88.3%, respectively, of enrolled patients were women. Overall, AEs were generally mild to moderate (AT studies: 82.3%-90.0%; STP studies: 78.9%89.5%). In AT1, 27.3% (131/480) of frovatriptan patients, 33.4% (161/482) of sumatriptan patients, and 14.8% (36/244) of placebo patients experienced an AE considered possibly or probably related to treatment (P < 0.001 for either drug vs placebo).There were no significant differences between frovatriptan and sumatriptan in SNAE at 4 to 24 hours or in SPRNAE at 2 to 24 hours or at 4 to 24 hours. In randomized, controlled STP trials for MM, AEs were reported by 57.8% (166/287, BID) and 63.4% (210/331, once daily) of frovatriptan users versus 62.8% (216/344) of placebo recipients. There were no consistent differences in AEs reported by patients with potential cardiovascular risk or in AEs related to the use of estrogencontaining contraceptives (ECCs).
  
  
  CONCLUSIONS
  In randomized controlled trials and 12-month open-label studies, frovatriptan was well tolerated in these women during AT and STP therapy for MM. Subgroup analyses provide preliminary evidence of tolerability in women using ECCs and in women with comorbidities that do not contraindicate triptan use but may be suggestive of cardiovascular risk.
authors.affiliation: The City of London Migraine Clinic, London, United Kingdom. anne.macgregor@migraineclinic.org.uk
authors.forename: E Anne
authors.initials: EA
authors.lastname: MacGregor
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Pawsey
authors.forename: John C
authors.initials: JC
authors.lastname: Campbell
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Hu
mesh_terms: D000208:Acute Disease; D002227:Carbazoles / Q000009:adverse effects / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000209:etiology; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008599:Menstruation Disturbances / Q000188:drug therapy / Q000517:prevention & control; D008881:Migraine Disorders / Q000188:drug therapy / Q000517:prevention & control; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012449:Safety; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use; D018170:Sumatriptan / Q000627:therapeutic use; D016896:Treatment Outcome; D014363:Tryptamines / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D002227:Carbazoles; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; D018170:Sumatriptan; C108128:frovatriptan