A double-blind study of diflunisal and codeine compared with codeine or diflunisal alone in postoperative pain

A double-blind, randomized, parallel-group study compared the analgesic efficacy of a single oral dose of 500 mg diflunisal, 60 mg codeine, 500 mg diflunisal plus 60 mg codeine given as separate agents, and placebo in 161 patients with moderate to severe postoperative pain. Standard subjective measures were used to evaluate analgesia. Eight-hour sum of pain intensity differences and total pain relief scores for all active treatments were significantly better than were those for placebo (p less than 0.05). Diflunisal plus codeine performed the best followed by diflunisal, codeine, and placebo. Diflunisal plus codeine was better than placebo from 1 1/2 to 8 hours (p less than 0.01), better than codeine from 1 1/2 to 6 hours (p less than 0.05), and better than diflunisal alone from 1/2 to 1 1/2 hours (p less than 0.05) for most measures of analgesia. Factorial analysis demonstrated a significant early codeine effect and a significant diflunisal effect throughout. No significant treatment group differences were observed regarding adverse effects. Our data demonstrate that diflunisal plus codeine is generally well tolerated and provides analgesia superior to that of diflunisal or codeine alone in the treatment of moderate to severe postoperative pain.