Analgesic efficacy and safety of tramadol/ acetaminophen combination tablets (Ultracet) in treatment of chronic low back pain: a multicenter, outpatient, randomized, double blind, placebo controlled trial.
OBJECTIVE
To evaluate the analgesic efficacy and safety of tramadol 37.5 mg/acetaminophen 325 mg (tramadol/APAP) combination tablets for treatment of chronic low back pain (LBP).


METHODS
This 91 day, multicenter, outpatient, randomized, double blind, placebo controlled study enrolled 338 patients with chronic LBP requiring daily medication for > or = 3 months. Patients with at least moderate pain [pain visual analog scale (VAS) with scores > or = 40/100 mm] after washout were randomized to tramadol/APAP or placebo. After a 10 day titration, patients received 1 or 2 tablets QID. Primary outcome measure was final pain VAS score. Secondary measures included pain relief, quality of life and physical functioning, efficacy failure, and overall medication assessments.


RESULTS
In total, 336 intent-to-treat patients received tramadol/APAP (n = 167) or placebo (n = 169). Mean baseline pain VAS score was 67.8. Intent-to-treat analysis showed significantly better mean final pain VAS scores (47.4 vs 62.9; p < 0.001) and mean final pain relief scores (1.8 vs 0.7; p < 0.001) for tramadol/APAP than for placebo. Roland Disability Questionnaire scores and physical-related subcategories of the McGill Pain Questionnaire and the Medical Outcome Study Short Form-36 Health Survey were significantly better for tramadol/APAP patients. More patients rated tramadol/APAP as "very good" or "good" than placebo (63.6 vs 25.2%; p < 0.001). Kaplan-Meier estimates of cumulative discontinuation rates due to efficacy failures were 22.9% (tramadol/APAP) vs 54.7% (placebo; p < 0.001). The most common treatment related adverse events with tramadol/APAP were nausea (12.0%), dizziness (10.8%), and constipation (10.2%). Average daily dose of tramadol/APAP was 4.2 tablets (tramadol 158 mg/APAP 1369 mg).


CONCLUSIONS
Tramadol 37.5 mg/APAP 325 mg combination tablets show efficacy in pain reduction, in measures of physical functioning and quality of life, and in overall medication assessments, with a tolerability profile comparable with other opioids used for the treatment of chronic LBP.
Peloso
Paul M
PM
Division of Rheumatology, Roy and Lucille Carver College of Medicine, University of Iowa Health Care E330 GH, 200 Hawkins Drive, Iowa City, IA 52242, USA. ppeloso@adelphia.net
Fortin
Luc
L
Beaulieu
André
A
Kamin
Marc
M
Rosenthal
Norman
N
D000082:Acetaminophen / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017116:Low Back Pain / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D011336:Probability; D012016:Reference Values; D012720:Severity of Illness Index; D014147:Tramadol / Q000008:administration & dosage*; D016896:Treatment Outcome
D018712:Analgesics, Non-Narcotic; D004338:Drug Combinations; C478659:Ultracet; D000082:Acetaminophen; D014147:Tramadol