title: Fixed-dose sumatriptan and naproxen in poor responders to triptans with a short half-life.
abstract: OBJECTIVE
  To evaluate efficacy and tolerability of a single, fixed-dose tablet of sumatriptan 85 mg/naproxen sodium 500 mg (sumatriptan/naproxen sodium) vs placebo in migraineurs who had discontinued treatment with a short-acting triptan because of poor response or intolerance.
  
  
  BACKGROUND
  Triptan monotherapy is ineffective or poorly tolerated in 1 of 3 migraineurs and in 2 of 5 migraine attacks. In April, 2008, the Food and Drug Administration approved the combination therapy sumatriptan/naproxen sodium, developed specifically to target multiple migraine mechanisms. This combination product offers an alternative migraine therapy for patients who have reported poor response or intolerance to short-acting triptans.
  
  
  METHODS
  Two replicate, randomized, multicenter, double-blind, placebo-controlled, 2-attack crossover trials evaluated migraineurs who had discontinued a short-acting triptan in the past year because of poor response or intolerance. Patients were instructed to treat within 1 hour and while pain was mild.
  
  
  RESULTS
  Patients (n = 144 study 1; n = 139 study 2) had discontinued an average of 3.3 triptans before study entry. Sumatriptan/naproxen sodium was superior (P < .001) to placebo for 2- through 24-hour sustained pain-free response (primary end point) (study 1, 26% vs 8%; study 2, 31% vs 8%) and pain-free response 2 hours post dose (key secondary end point) (study 1, 40% vs 17%; study 2, 44% vs 14%). A similar pattern of results was observed for other end points that evaluated acute (2- or 4-hour), intermediate (8-hour), or 2- through 24-hour sustained response for migraine (ie, pain and associated symptoms), photophobia, phonophobia, or nausea (with the exception of nausea 2 and 4 hours post dose). The percentage of patients with at least 1 adverse event (regardless of causality) was 11% with sumatriptan/naproxen sodium compared with 4% with placebo in study 1 and 9% with sumatriptan/naproxen sodium compared with 5% with placebo in study 2. Only 1 adverse event in 1 study was reported in > or =2% of patients after treatment with sumatriptan/naproxen sodium and reported more frequently with sumatriptan/naproxen than placebo: chest discomfort was reported in 2% of subjects in study 1, and no events met this threshold in study 2. No serious adverse events attributed to study medication were reported in either study.
  
  
  CONCLUSIONS
  In migraineurs who reported poor response to a short-acting triptan, sumatriptan/naproxen sodium was generally well tolerated and significantly more effective than placebo in conferring initial, intermediate, and sustained efficacy for pain and migraine-associated symptoms of photophobia and phonophobia.
authors.affiliation: Houston Headache Clinic, Houston, 1213 Hermann Drive, Suite 820, Houston, TX 77004, USA.
authors.forename: Ninan T
authors.initials: NT
authors.lastname: Mathew
authors.forename: Stephen
authors.initials: S
authors.lastname: Landy
authors.forename: Stuart
authors.initials: S
authors.lastname: Stark
authors.forename: Gretchen E
authors.initials: GE
authors.lastname: Tietjen
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Derosier
authors.forename: Jonathan
authors.initials: J
authors.lastname: White
authors.forename: Shelly E
authors.initials: SE
authors.lastname: Lener
authors.forename: Deo
authors.initials: D
authors.lastname: Bukenya
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D009288:Naproxen / Q000627:therapeutic use*; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*; D018170:Sumatriptan / Q000627:therapeutic use*; D016896:Treatment Outcome; D014363:Tryptamines / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D016861:Cyclooxygenase Inhibitors; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; D009288:Naproxen; D018170:Sumatriptan