Tramadol/acetaminophen combination tablets and codeine/acetaminophen combination capsules for the management of chronic pain: a comparative trial.

BACKGROUND

Opioid/acetaminophen (APAP) combination analgesics are widely prescribed for the relief of moderate pain. Tramadol is a synthetic analgesic that has been shown to be effective both alone and in combination with APAP.

OBJECTIVE

The purpose of this study was to compare the efficacy and tolerability of tramadol/APAP tablets with codeine/APAP capsules.

METHODS

This 4-week, randomized, double-blind, parallel-group, active-control, double-dummy, multicenter trial compared tramadol/APAP (37.5 mg/325 mg) with codeine/APAP (30 mg/300 mg) for the management of chronic nonmalignant low back pain, osteoarthritis (OA) pain, or both in adults. Pain relief (scale, 0 = none to 4 = complete) and pain intensity (scale, 0 = none to 3 = severe) were measured 30 minutes and then hourly for 6 hours after the first daily dose each week. Patients and investigators assessed the efficacy (scale, 1 = poor to 5 = excellent) of each medication, and patients recorded daily doses of study and rescue medications.

RESULTS

A total of 462 patients (mean age, 57.6 years) were randomly assigned to treatment, with 112 (24%) reporting chronic low back pain, 162 (35%) reporting OA pain, and 188 (41%) reporting both low back and OA pain; 309 patients (67%) received tramadol/APAP and 153 (33%) received codeine/APAP. Pain relief and changes in pain intensity were comparable from day 1, as early as 30 minutes after the first dose, and lasted for at least 6 hours. Total pain relief scores (11.9 for tramadol/APAP; 11.4 for codeine/APAP) and sum of pain intensity differences (3.8 for tramadol/APAP; 3.3 for codeine/APAP) were also comparable throughout. Overall assessments of efficacy by patients (mean score 2.9 in each treatment group) and investigators (mean score 3.0 for tramadol/APAP, 2.9 for codeine/APAP) were similar for the 2 treatment groups. Equivalent mean doses (3.5 tablets or capsules daily) and maximum daily doses (5.5 tablets or 5.7 capsules) were used in the 2 treatment groups. The overall incidence of adverse events was comparable, with a significantly higher proportion of patients in the codeine/APAP group reporting somnolence (24% [37/153] vs 17% [54/309], P = 0.05) or constipation (21% [32/153] vs 11% [35/309], P < 0.01) and a larger proportion of patients in the tramadol/APAP group reporting headache (11% [34/309] vs 7% [11/153], P = 0.08).

CONCLUSION

The results of this study suggest that tramadol/APAP tablets (37.5 mg/325 mg) are as effective as codeine/ APAP capsules (30 mg/300 mg) in the treatment of chronic nonmalignant low back pain and OA pain and are better tolerated.