title: Tramadol and acetaminophen tablets for dental pain.
abstract: The purpose of this work was to compare the efficacy and time to analgesia of a new tramadol/acetaminophen combination tablet to those of tramadol or acetaminophen (APAP) alone. A meta-analysis was performed of 3 separate single-dose, double-blind, parallel-group trials in patients with moderate or severe pain following extraction of 2 or more third molars. Patients in each study were evenly randomized to a single dose of tramadol/APAP (75 mg/650 mg), tramadol 75 mg, APAP 650 mg, ibuprofen 400 mg, or placebo. Active control with ibuprofen was used to determine model sensitivity. Pain relief (scale, 0-4) and pain intensity (scale, 0-3) were reported at 30 minutes after the dose and then hourly for 8 hours. Total pain relief over 8 hours (TOTPAR8) and the sum of pain intensity differences (SPID8) were calculated from the hourly scores. Time to onset of pain relief was determined by the double-stopwatch technique, and patients were advised to wait at least 2 hours before taking supplemental analgesia. Patients assessed overall efficacy (scale, 1-5) upon completion. In all, 1197 patients (age range, 16-46 years) were evaluable for efficacy; treatment groups in each study were similar at baseline. Pain relief was superior to placebo (P < or = .0001) for all treatments. Pain relief provided by tramadol/ APAP was superior to that of tramadol or APAP alone, as shown by mean TOT-PAR8 (12.1 vs 6.7 and 8.6, respectively, P < or = .0001) and SPID8 (4.7 vs 0.9 and 2.7, respectively, P < or = .0001). Estimated onset of pain relief was 17 minutes (95% CI, 15-20 minutes) for tramadol/APAP compared with 51 minutes (95% CI, 40-70 minutes) for tramadol, 18 minutes (95% CI, 16-21 minutes) for APAP, and 34 minutes (95% CI, 28-44 minutes) for ibuprofen. Median time to supplemental analgesia and mean overall assessment of efficacy were greater (P < .05) for the tramadol/APAP group (302 minutes and 3.0, respectively) than for the tramadol (122 minutes and 2.0) or APAP (183 minutes and 2.7) monotherapy groups. A new combination analgesic, tramadol/APAP, is superior to tramadol or APAP alone with respect to pain relief and duration of action. It is also superior to tramadol alone with respect to time to onset.
authors.affiliation: Robert Wood Johnson Pharmaceutical Research Institute, Raritan, New Jersey, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Medve
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Karim
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000704:Analysis of Variance; D019162:Anesthetics, Combined; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D004311:Double-Blind Method; D005157:Facial Pain / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D008964:Molar, Third / Q000601:surgery; D010147:Pain Measurement; D013997:Time Factors; D014081:Tooth Extraction / Q000009:adverse effects*; D014147:Tramadol / Q000008:administration & dosage*
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D019162:Anesthetics, Combined; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen; D014147:Tramadol; D007052:Ibuprofen