Codeine is widely used in combination with
acetaminophen and
aspirin for the management of mild to moderate
pain. However, there are few controlled clinical trials of single-entity
codeine in chronic
cancer pain. The purpose of this study was to evaluate the clinical efficacy and safety of controlled-release
codeine given every 12 hr in patients with
cancer pain. Thirty-five patients with chronic
cancer pain were randomized in a double-blind crossover study to controlled-release (CR)
codeine or placebo, for 7 days each.
Pain intensity was assessed at 0800 hr and 2000 hr using a visual analogue scale (VAS) and a five-point categorical scale, and the use of "rescue"
acetaminophen-plus-
codeine (300 mg/30 mg every 4 hr as needed) was recorded. Thirty patients completed the study (17 male, 13 female; mean age, 64.4 +/- 9.8 years) with a mean daily CR
codeine dose of 277 +/- 77 mg (range, 200-400 mg). CR
codeine treatment resulted in significantly lower overall VAS
pain intensity scores (22 +/- 18 mm versus 36 +/- 20 mm, P = 0.0001), categorical
pain intensity scores (1.2 +/- 0.8 versus 1.8 +/- 0.8, P = 0.0001), and
pain scores when assessed by day of treatment and by time of day. Daily "rescue"
analgesic consumption was significantly lower on CR
codeine, compared to placebo treatment (2.2 +/- 2.3 versus 4.6 +/- 2.8
tablets per day, P = 0.0001). Both patients and investigators preferred CR
codeine to placebo (80% versus 3%, P = 0.0014 and 73% versus 7%, P = 0.0160, respectively). These data indicate that CR
codeine, given every 12 hr results in significant reductions in
pain intensity and the use of "rescue"
acetaminophen-plus-
codeine in patients with
cancer pain. CR
codeine provides the benefits of a flexible single entity
codeine formulation and the convenience of 12-hr duration of action, which allows patients uninterrupted sleep and improved compliance.