[Problem forte--is paracetamol-codeine combination rational?].
BACKGROUND
Combination drugs containing codeine and paracetamol are widely prescribed in Norway.


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.


CONCLUSIONS
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.
Helland
Arne
A
Institutt for laboratoriemedisin, barne- og kvinnesykdommer, Norges teknisk-naturvitenskapelige universitet, 7489 Trondheim.
Spigset
Olav
O
Slørdal
Lars
L
D000082:Acetaminophen / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics; D000208:Acute Disease; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics; D002908:Chronic Disease; D003061:Codeine / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D004338:Drug Combinations; D006801:Humans; D010146:Pain / Q000188:drug therapy
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D004338:Drug Combinations; C526278:acetaminophen, codeine drug combination; D000082:Acetaminophen; D019389:Cytochrome P-450 CYP2D6; D003061:Codeine