title: Tramadol/acetaminophen combination tablets for the treatment of osteoarthritis flare pain: a multicenter, outpatient, randomized, double-blind, placebo-controlled, parallel-group, add-on study.
abstract: BACKGROUND
  In a flare of osteoarthritis (OA) pain, increasing the dose of standard anti-inflammatory or routine analgesic drugs may not be practical because of an increased incidence of side effects. In patients achieving inadequate pain relief from traditional non-steroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase (COX)-2-selective inhibitors, it may be appropriate to add an analgesic agent with a different mechanism of action, thereby targeting multiple components of the pain pathway.
  
  
  OBJECTIVE
  The addition of tramadol/acetaminophen tablets to existing therapy was compared with the addition of placebo in the treatment of OA flare pain.
  
  
  METHODS
  This was a multicenter, outpatient, randomized, double-blind, placebo-controlled, parallel-group, add-on study. Patients received 1 or 2 tramadol/acetaminophen (37.5 mg/325 mg) tablets QID or matching placebo for 10 days in addition to ongoing NSAID or COX-2-selective inhibitor therapy. The primary outcome measures were average daily pain intensity and average daily pain relief scores from days 1 through 5.
  
  
  RESULTS
  Three hundred eight patients were randomized to tramadoUacetaminophen (n = 197) or placebo (n = 111) and were followed for up to 10 days. Patients had a mean (+/-SD) age of 60.1 +/- 9.87 years, and were predominantly female (71.8%) and white (87.7%). Their mean (+/- SD) pain visual analog score at baseline was 73.2 +/- 11.8 mm, and their mean pain intensity score was 2.4 +/- 0.5 (on a scale from 0 = none to 3 = severe). Average daily pain intensity and pain relief scores were significantly improved with tramadol/acetaminophen compared with placebo on the primary assessment of efficacy from days 1 through 5 (both, P < 0.001) and on the assessment of efficacy from days I through 10 (both, P < 0.001) Tramadol/acetaminophen was significantly superior to placebo on the patients' and physicians' overall assessments of medication (both, P < 0.001) and on 3 of 4 subscales (pain [P = 0.004], physical function [P = 0.013], and overall [P = 0.008]) of the Western Ontario and McMaster Universities Osteoarthritis Index Questionnaire. The most common treatment-emergent adverse events with tramadol/acetaminophen were nausea, vomiting, and dizziness. No serious adverse events were reported in the tramadol/acetaminophen group.
  
  
  CONCLUSIONS
  In this study, addition of tramadol/acetaminophen to NSAID or COX-2-selective inhibitor therapy was well tolerated and effective in the treatment of OA flare pain.
authors.affiliation: Tampa Medical Group, PA, Florida 33614, USA.
authors.forename: Joel C
authors.initials: JC
authors.lastname: Silverfield
authors.forename: Marc
authors.initials: M
authors.lastname: Kamin
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Wu
authors.forename: Norman
authors.initials: N
authors.lastname: Rosenthal
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000627:therapeutic use*; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy*; D014147:Tramadol / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D004338:Drug Combinations; D000082:Acetaminophen; D014147:Tramadol