Tramadol/acetaminophen combination tablets for the treatment of osteoarthritis flare pain: a multicenter, outpatient, randomized, double-blind, placebo-controlled, parallel-group, add-on study

Clin Ther. 2002 Feb;24(2):282-97. doi: 10.1016/s0149-2918(02)85024-x.


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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / therapeutic use*
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Cyclooxygenase Inhibitors / therapeutic use
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Humans
  • Male
  • Middle Aged
  • Osteoarthritis / drug therapy*
  • Pain / drug therapy*
  • Tramadol / administration & dosage
  • Tramadol / therapeutic use*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Drug Combinations
  • Acetaminophen
  • Tramadol