[Problem forte--is paracetamol-codeine combination rational?]

Abstract

Background: Combination drugs containing codeine and paracetamol are widely prescribed in Norway.

Material and methods: We reviewed relevant literature identified through searches on Medline or found in the reference lists of important articles.

Results: Codeine mediates its analgesic effect through the active metabolite morphine, a reaction which is catalysed by the cytochrome P450-isoenzyme CYP2D6. Approximately 7-10 % of the population does not express functional CYP2D6; for them codeine have no analgesic effect. They may, however, experience side effects from codeine. Used alone, codeine is an inefficient analgesic. Meta-analyses have shown little therapeutic advantage by adding codeine to paracetamol.

Interpretation: Codeine is an opiate with uncertain and unpredictable effects. The therapeutic benefit from the codeine component in combination with paracetamol is small, even in single dose evaluations. In chronic use, the therapeutic efficacy is most likely outweighed by side effects, including development of tolerance and abuse.