ABSTRACT
OBJECTIVE: The clinical utility of guidelines for conversion of patients from a combination analgesic preparation of acetaminophen 300 mg plus codeine 30 mg every 4h to 6h as needed to scheduled controlled-release (CR) codeine every 12h was evaluated. METHODS: Adult patients with chronic noncancer pain underwent a two-week evaluation on acetaminophen plus codeine, followed by eight weeks of treatment with CR codeine. Patients taking four to six tablets of acetaminophen plus codeine per day were transferred to 50 mg CR codeine every 12 h; those on seven to nine tablets were transferred to 100 mg every 12 h; those on 10 to 12 tablets were transferred to 150 mg every 12 h; and those on greater than 12 tablets were transferred to 200 mg every 12 h. Subsequent dose adjustments were permitted. Acetaminophen (325 mg) was available for rescue. Pain intensity (five-point categorical and 100 mm visual analog scale), pain related disability, adverse events and acceptability were assessed. RESULTS: Of the 140 patients enrolled, 95 completed eight weeks of treatment with CR codeine. During month 1 and month 2, the mean CR codeine daily doses were 295.7+/-119.1 mg and 390.3+/-163.4 mg, respectively. Pain scores during both CR codeine month 1 and 2 were significantly lower than on acetaminophen plus codeine (53.6+/-20.9 mm and 49.7+/-23.7 mm versus 59.6+/-17.5 mm; P=0.0003, P=0.0001, respectively). CR codeine treatment was rated as moderately or highly acceptable by 82% of patients compared with 50% for acetaminophen plus codeine (P=0.001). Only seven patients (5.9%) discontinued CR codeine treatment because of adverse events. CONCLUSION: The results confirm the safety, efficacy and patient acceptability of the initial conversion and maintenance dosing recommendations for CR codeine from a combination opioid/nonopioid analgesic.
Subject(s)
Codeine/administration & dosage , Pain/drug therapy , Adult , Chronic Disease , Codeine/adverse effects , Delayed-Action Preparations/administration & dosage , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Evaluation/methods , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Pain/physiopathology , Practice Guidelines as Topic/standardsABSTRACT
Treatment decisions for the use of opioid analgesics in chronic non-malignant pain are based primarily on survey data, as evidence from well-controlled clinical trials has been lacking. Forty-six patients with chronic non-malignant pain were enrolled in a randomized, double-blind, placebo-controlled evaluation of controlled-release (CR) codeine. Following a 3-7-day diary familiarization period, patients were randomly assigned to 7 days of treatment each with CR codeine q12h or placebo. The CR codeine dose was determined from the consumption of acetaminophen+codeine in the 7 days preceding the study. During both phases, breakthrough pain was treated with acetaminophen+codeine every 4 h as required. Pain intensity was assessed at 08:00 h and 20:00 h using a visual analogue scale (VAS) and a 5-point categorical scale, and rescue analgesic consumption was recorded at the time of use. Thirty patients (17 female, 13 male; mean age: 55.1 +/- 13.4 years) completed the study and were treated with a mean daily CR codeine dose of 273 +/- 78 mg (range: 200-400 mg). CR codeine treatment resulted in significantly lower overall VAS pain intensity scores (35 +/- 18 vs. 49 +/- 16, P = 0.0001), categorical pain intensity scores (1.7 +/- 0.6 vs. 2.2 +/- 0.6, P = 0.0001), and in pain scores by day of treatment and by time of day. Daily rescue analgesic consumption was significantly lower on CR codeine, relative to placebo treatment (3.6 +/- 3.5 vs. 6.1 +/- 3.2 tablets/day, P = 0.0001). There was also a significant reduction in the Pain Disability Index (PDI) on CR codeine, compared to placebo (25.0 +/- 7.7 vs. 35.1 +/- 8.2, P = 0.0001). Patients' and investigators' blinded treatment preference was significantly in favor of CR codeine, relative to placebo (73% vs. 10%, P = 0.0160 and 80% vs. 7%, P = 0.0014, respectively). The incidence of nausea was significantly higher on CR codeine than on placebo (32.6% vs. 11.9%, P = 0.013). Ninety-three percent of patients completing the study requested long-term, open-label treatment with CR codeine. Pain intensity scores at the completion of 19 weeks of long-term evaluation were comparable to those during the double-blind CR codeine treatment. We conclude that treatment with CR codeine results in reduced pain and pain-related disability in patients with chronic non-malignant pain.