Codeine plus acetaminophen: benefits and side effects - adapted from the British Medical Journal 199

Author: Anne D. Walling
Date: Nov 15, 1996

Acetaminophen is believed to produce analgesia primarily through peripheral effects. It has become widely used for analgesia both under medical supervision arid as an over-the-counter agent. Codeine is believed to act mainly within the central nervous system and is frequently used when analgesia with acetaminophen alone is inadequate. Although the combination of the two agents is believed to enhance the analgesic effect without increasing side effects, the efficacy and safety of the combination has not been determined. De Craen and colleagues reviewed the evidence comparing acetaminophen alone and combinations of acetaminophen with codeine for analgesia.

In addition to published studies, the researchers accessed information from drug manufacturers and reference lists. They identified 29 clinical trials that met their criteria for methodologic and statistical quality. Five of these trials were excluded because of internal discrepancies or duplication of another paper. Twenty-one of the 24 remaining trials were predominantly concerned with postoperative pain. Trials that evaluated postpartum pain, osteoarthritis and experimentally induced pain were also identified. The dosages used ranged from 400 to 1,000 mg of acetaminophen and 10 to 60 mg of codeine. The studies varied in design, duration of follow-up and intensity of treatment.

For studies of single-dose treatment, the addition of codeine was calculated to increase analgesic effect by approximately 5 percent. In these studies, the incidence of side effects was similar between acetaminophen alone and combination therapy. The incidence of side effects was significantly increased when combination treatments were used in multidose studies.

The authors conclude that the addition of codeine to acetaminophen provides a significantly increased analgesic effect but an increased incidence of side effects. These effects included nausea, dizziness, drowsiness and constipation when codeine was taken in more than one dose. The authors endorse the occasional use of combination therapy as a single dose when enhanced analgesia is required, but caution that repeated use of combination medications increases the occurrence of side effects.

De Craen AJ, et al. Analgesic efficacy and safety of paracetamol-codeinz combinatioms versus paracetamol alone: a systematic review. BMJ 1996;313:321-5.

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