title: Long-term safety of naproxen and esomeprazole magnesium fixed-dose combination: phase III study in patients at risk for NSAID-associated gastric ulcers.
abstract: OBJECTIVE
  To evaluate long-term safety of enteric-coated naproxen 500 mg and immediate-release esomeprazole magnesium 20 mg fixed-dose combination (FDC) in patients at risk of NSAID-associated upper gastrointestinal (UGI) ulcers.
  
  
  METHODS
  In this open-label, multicenter, phase III study, Helicobacter pylori-negative patients aged ≥50 years or 18-49 years with history of uncomplicated ulcer within the past 5 years, who had osteoarthritis, rheumatoid arthritis, or other condition requiring daily NSAIDs for ≥12 months received naproxen/esomeprazole twice daily for 12 months.
  
  
  BACKGROUND
  NCT00527904.
  
  
  METHODS
  Adverse events (AEs), vital signs, physical examination, and laboratory tests. Subgroup analyses included age and low-dose aspirin (LDA) use. Predefined NSAID-associated UGI and cardiovascular AEs were analyzed.
  
  
  RESULTS
  Of 239 patients treated (safety population), 135 completed ≥348 treatment days (12-month completers). AE incidence was approximately 70%; dyspepsia, constipation, upper respiratory tract infection, nausea, back pain, and contusion were most frequent (≥5% patients, either population). Treatment-related AEs occurred in 28.0% and 23.7% of patients in the safety and 12-month completer populations, respectively; 18.8% of patients withdrew due to AEs (safety population). Few serious AEs and no deaths occurred. In the safety population, AE incidence was 71.4% and 76.9% in patients aged <65 years (n = 161) and ≥65 years (n = 78), respectively, and 67.6% and 75.8% in LDA users (n = 74) and non-users (n = 165), respectively. Predefined UGI and cardiovascular AEs were observed in 18.8% and 6.3% of patients, respectively, in the safety population, and 16.3% and 5.2%, respectively, in 12-month completers. Dyspepsia and hypertension were most common. Additional assessments showed no unexpected findings.
  
  
  CONCLUSIONS
  Based on these outcome measures, long-term treatment with FDC naproxen/esomeprazole is not associated with any new safety issues, including predefined UGI and cardiovascular AEs, in patients requiring NSAID therapy who are at risk of UGI complications.
authors.affiliation: AstraZeneca, Wilmington, DE, USA. Mark.Sostek@AstraZeneca.com
authors.forename: Mark B
authors.initials: MB
authors.lastname: Sostek
authors.forename: John G
authors.initials: JG
authors.lastname: Fort
authors.forename: Lennart
authors.initials: L
authors.lastname: Estborn
authors.forename: Kerstin
authors.initials: K
authors.lastname: Vikman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004304:Dosage Forms; D004338:Drug Combinations; D064098:Esomeprazole / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D017616:Magnesium Compounds / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000008:administration & dosage* / Q000009:adverse effects; D010003:Osteoarthritis / Q000188:drug therapy*; D012307:Risk Factors; D013276:Stomach Ulcer / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D004304:Dosage Forms; D004338:Drug Combinations; D017616:Magnesium Compounds; D009288:Naproxen; D064098:Esomeprazole