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Codeine

Classification: B

Drug products: Altermol, Ardinex®, Burana Comp, Citodon®, Citodon® forte, Citodon® minor, Codalvonil, Kodein Alternova, Kodein Meda, Kodeinfosfat APL, Panocod®, Paracetamol/Kodein Evolan, Treo® comp

ATC code: A07DA, N02AJ06, N02AJ08, N02AJ09, R05DA04

Substances: codeine, codeine hydrobromide, codeine hydrochloride, codeine phosphate, codeine phosphate anhydrous, codeine phosphate hemihydrate, codeine phosphate, sesquihydrate

Summary

Controlled studies on differences between men and women in effect, safety, and pharmacokinetics of codeine are lacking. Codein is a pro-drug of morphine and the effects and adverse effects are derived from morphine (see separate document on morphine).
 
The present evidence concerning differences between men and women is limited and do not motivate differentiation in dosing or treatment.

Additional information

Pharmacokinetics and dosing

Codeine is metabolized to its active metabolite morphine by the CYP2D6 isoenzyme. The activity of this isoenzyme is reported to be unaltered by sex [1, 2]. Clinical studies have shown effect with similar doses in men and women and no sex differentiation in dosing has been suggested [3].

Effects

A small randomized controlled study in healthy volunteers (9 men, 7 women) found that women were more sensitive to respiratory depression of 60 mg oral codeine [4].

Adverse effects

In a double-blind trial evaluating the analgesic effect and adverse events of 1000 mg paracetamol/60 mg codeine after tooth extraction (44 men, 50 women) women were found to report more adverse events. The mean weight was 76 kg and 62 kg in men and women, respectively, and might explain the difference [5].

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Updated: 2019-02-26

Date of litterature search: 2015-02-19

References

  1. Franconi F, Brunelleschi S, Steardo L, Cuomo V. Gender differences in drug responses. Pharmacol Res. 2007;55:81-95. PubMed
  2. Nicolson TJ, Mellor HR, Roberts RR. Gender differences in drug toxicity. Trends Pharmacol Sci. 2010;31:108-14. PubMed
  3. Citodon (kodein). Summary of Product Characteristics. Medical Products Agency - Sweden; 2014.
  4. Pleuvry BJ, Maddison SE. A sex difference in the effects of oral codeine and promethazine on the ventilatory response to carbon dioxide in human volunteers. Br J Clin Pharmacol. 1980;9:159-64. PubMed
  5. Sagne S, Henrikson PA, Kahnberg KE, Thilander H, Bertilson SO. Analgesic efficacy and side-effect profile of paracetamol/codeine and paracetamol/dextropropoxyphene after surgical removal of a lower wisdom tooth. J Int Med Res. 1987;15:83-8. PubMed
  6. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-30.] länk

Authors: Linnéa Karlsson Lind, Desirée Loikas

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson