This multicenter, randomized, double-blind, active- and placebo-controlled trial evaluated tramadol plus acetaminophen (APAP) for orthopedic (n = 153) and abdominal (n = 152) postsurgical pain.

Patients with moderate pain or greater were randomized to an initial two tablets of 37.5 mg tramadol plus 325 mg APAP (n = 98), codeine 30 mg plus APAP 300 mg (n = 109), or placebo (n = 98); thereafter, they received 1 to 2 tablets every 4 to 6 hours as needed for pain for 6 days. Outcome measures were pain relief and pain intensity, total pain relief, sum of pain intensity differences, and sum of pain relief and pain intensity differences during 4 hours and the daily averages.

Tramadol plus APAP was superior to placebo for total pain relief, sum of pain intensity differences, and sum of pain relief and pain intensity differences (P ≤0.015); tramadol plus APAP and codeine plus APAP did not separate (P ≥0.281). For average daily pain relief, average daily pain intensity, and overall medication assessment, tramadol plus APAP was superior to placebo (P ≤0.038); codeine plus APAP did not separate from placebo (P ≥0.125). Discontinuation because of adverse events occurred in 8.2% of tramadol plus APAP, 10.1% of codeine plus APAP, and 3.0% of placebo patients. Except for constipation (4.1% tramadol plus APAP vs 10.1% codeine plus APAP) and vomiting (9.2% vs 14.7%, respectively), adverse events were similar for active treatments.

Tramadol plus APAP (mean dose 4.4 tablets) was effective and well tolerated for postsurgical pain and showed better tolerability than did codeine plus APAP.