title: One-year safety of ibuprofen/famotidine fixed combination versus ibuprofen alone: pooled analyses of two 24-week randomized, double-blind trials and a follow-on extension.
abstract: OBJECTIVE
  To evaluate the safety of the fixed combination of ibuprofen and famotidine compared with ibuprofen alone from two 24-week, multicenter, double-blind trials designed to evaluate the comparative incidence of endoscopically documented upper gastrointestinal ulcers and a 28-week double-blind extension study.
  
  
  METHODS
  Safety was analyzed by pooling data from the two double-blind trials and the follow-on study. Safety was assessed by monitoring the incidence, causality, and severity of adverse events (AEs).
  
  
  RESULTS
  In the pivotal efficacy and safety trials, discontinuation rates due to any cause and dyspepsia were significantly lower for the ibuprofen/famotidine combination versus ibuprofen alone. Other than dyspepsia, gastrointestinal and cardiovascular AEs of special interest were similar. Events judged to be treatment related were significantly lower with the ibuprofen/famotidine combination (20.6% vs. 25%). In the safety extension population, there were no differences in the discontinuation rates and the reporting of AEs or serious AEs (SAEs) between the two groups. Gastrointestinal-related events were similar between the groups. Incidence of cardiovascular-related AEs of special interest were 11% (ibuprofen/famotidine) and 2% (ibuprofen) (p=0.06), possibly due to a higher number of rheumatoid arthritis patients in the combination group. Of these, 80% were reports of hypertension (8% ibuprofen/famotidine vs. 2% ibuprofen). Three cases of hypertension in the ibuprofen/famotidine group were considered treatment related. The probability of a cardiovascular event decreased during days 112-167 of treatment and remained low with continued treatment.
  
  
  CONCLUSIONS
  One-year safety data from two pivotal trials and a long-term extension study indicate that the ibuprofen/famotidine combination demonstrates a favorable gastrointestinal safety profile and more patients continued on therapy compared to ibuprofen alone. No new safety signals have been identified. These data offer additional evidence supporting a new therapeutic option to improve gastrointestinal safety and adherence for patients who require long-term ibuprofen.
authors.affiliation: University of Illinois-Chicago, College of Medicine, and Illinois Bone and Joint Institute LLC , Glenview, IL , USA.
authors.forename: Alfonso E
authors.initials: AE
authors.lastname: Bello
authors.forename: Amy Y
authors.initials: AY
authors.lastname: Grahn
authors.forename: Julie
authors.initials: J
authors.lastname: Ball
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Kent
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Holt
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D004338:Drug Combinations; D016903:Drug Monitoring / Q000379:methods; D004415:Dyspepsia / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control; D016099:Endoscopy, Gastrointestinal / Q000379:methods; D015738:Famotidine / Q000008:administration & dosage; D005260:Female; D006635:Histamine H2 Antagonists / Q000008:administration & dosage*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000175:diagnosis; D007052:Ibuprofen / Q000008:administration & dosage / Q000009:adverse effects; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D012720:Severity of Illness Index; D013276:Stomach Ulcer / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology / Q000517:prevention & control; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D006635:Histamine H2 Antagonists; D015738:Famotidine; D007052:Ibuprofen
keywords: Arthritis, rheumatoid; Cardiovascular; Famotidine; Gastrointestinal; Ibuprofen; Non-steroidal anti-inflammatory agents; Safety