Abstract

GONZALEZ-ESCALADA, J.R.. Pharmacological synergy applied to analgesia: review of the combination of ibuprofen with codeine. Rev. Soc. Esp. Dolor [online]. 2010, vol.17, n.1, pp.51-60. ISSN 1134-8046.

Multimodal analgesia, which is currently included in all postoperative analgesia protocols, is also used by specialists in chronic pain who routinely use drug combinations to optimize analgesic effectiveness; drug combination is a well-known and widespread practice due to its demonstrated therapeutic utility and is routinely used in both anesthesia and analgesia. The concept of an adequate balance between safety and effectiveness is essential. Although the quality of treatment is measured by the relief obtained, comfort is evaluated by taking into account the relation between analgesic efficacy and the absence, or minimal presence, of adverse effects, which is crucial in the treatment of patients with pain. The search for the minimum effective dose for each drug is crucial to achieve the optimal combination of doses. The search for drugs to form a combination and the doses to be used should be the result of research but should also be corroborated by clinical experience, expert opinion and published evidence. The present article provides an extensive review of clinical experience of the use of ibuprofen with codeine and analyzes the historical antecedents leading to the use of this combination, the studies demonstrating the synergy between these drugs and their pharmacokinetic compatibility and the pioneer clinical studies that allowed the optimal fixed dose of this combination to be defined as 400 mg of ibuprofen with 30 mg codeine. It is difficult to draw conclusions on the analgesic effectiveness of the distinct non-steroidal anti-inflammatory agents but, according to the data gathered to date, ibuprofen is undoubtedly among the most effective agents in this class and is a good option for inclusion in any galenic product combining analgesics. Numerous studies in acute pain indicate that ibuprofen only improves the efficacy of paracetamol and that of the combination of paracetamol and codeine. Studies comparing ibuprofen plus codeine with high-dose codeine show a highly significant difference (p > 0.05) in favor of the combination. Moreover, the differences are increased in studies of acute pain with multiple doses and in studies of chronic pain. The fixed-dose combination of ibuprofen plus codeine, recently introduced in Spain, fulfills all the criteria required for multimodal therapy and has been demonstrated to be an excellent therapeutic option for acute and chronic pain in the numerous studies reviewed.

Keywords : NSAID; Ibuprofen; Synergies; Opioids; Acute pain; Multimodal analgesia; Chronic pain.

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