Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Consensus Statement
  • Published:

A software tool to adjust codeine dose based on CYP2D6 gene-pair polymorphisms and drug-drug interactions

The Pharmacogenomics Journal volume 23, pages 217–224 (2023)Cite this article

Subjects

Abstract

Codeine is metabolized by the CYP2D6 enzyme, and individuals with certain genetic variations of the CYP2D6 gene may metabolize codeine differently, leading to variable efficacy and toxicity. Drug-drug interactions can also affect the metabolism of codeine. A tool to adjust codeine dose based on these factors does not currently exist. Healthcare providers should use their clinical judgment and reference different established dosing guidelines to determine the appropriate dose of codeine for individual patients. The study provides a tool that assists prescribers in adjusting codeine dose based on CYP2D6 gene-pair polymorphisms and drug-drug interactions. Highlighted is the need to consider pharmacogenetics and drug-drug interactions when determining the appropriate dosing of codeine and provide a framework for implementing individualized dosing based on these factors.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: AUC ratio versus activity scores 0.55–0.95.
Fig. 2: AUC ratio versus activity scores 0.05–0.45.
Fig. 3: AUC ratio versus activity scores for codeine.

Similar content being viewed by others

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. How codeine metabolism affects its clinical use. Pharm J [Internet]. 2021 [cited 2023 Jul 25]. Available from: https://pharmaceutical-journal.com/article/ld/how-codeine-metabolism-affects-its-clinical-use.

  2. Lam J, Woodall KL, Solbeck P, Ross CJD, Carleton BC, Hayden MR, et al. Codeine-related deaths: the role of pharmacogenetics and drug interactions. Forensic Sci Int. 2014;239:50–6.

    Article  CAS  PubMed  Google Scholar 

  3. Crews KR, Gaedigk A, Dunnenberger HM, Leeder JS, Klein TE, Caudle KE, et al. Clinical pharmacogenetics implementation consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharm Ther. 2014;95:376–82.

    Article  CAS  Google Scholar 

  4. Chidambaran V, Sadhasivam S, Mahmoud M. Codeine and opioid metabolism: implications and alternatives for pediatric pain management. Curr Opin Anaesthesiol. 2017;30:349–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Codeine label. Last accessed December 2022 [Internet]. [cited 2023 Apr 4]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022402s009lbl.pdf.

  6. Adam de Beaumais T, Jacqz-Aigrain E. Pharmacogenetics: applications to pediatric patients. In: Advances in pharmacology [Internet]. Elsevier; 2018. p. 191–215. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1054358918300255.

  7. Ma TKW, Lam YY, Tan VP, Yan BP. Variability in response to clopidogrel: how important are pharmacogenetics and drug interactions?: Clopidogrel response variability. Br J Clin Pharm. 2011;72:697–706.

    Article  CAS  Google Scholar 

  8. Saab Y, Zeenny R, Ramadan W. Optimizing clopidogrel dose response: a new clinical algorithm comprising CYP2C19 pharmacogenetics and drug interactions. Ther Clin Risk Manag. 2015;11:1421–7.

  9. Fulton CR, Zang Y, Desta Z, Rosenman MB, Holmes AM, Decker BS, et al. Drug–gene and drug–drug interactions associated with tramadol and codeine therapy in the INGENIOUS trial. Pharmacogenomics. 2019;20:397–408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. FDA table of substrates. Last accessed December 2022 [Internet]. [cited 2023 Apr 4]. Available from: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers.

  11. Lunenburg CATC, van der Wouden CH, Nijenhuis M, Crommentuijn-van Rhenen MH, de Boer-Veger NJ, Buunk AM, et al. Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene–drug interaction of DPYD and fluoropyrimidines. Eur J Hum Genet. 2020;28:508–17.

    Article  CAS  PubMed  Google Scholar 

  12. Ross CJD, Visscher H, Sistonen J, Brunham LR, Pussegoda K, Loo TT, et al. The Canadian Pharmacogenomics Network for Drug Safety: a model for safety pharmacology. Thyroid. 2010;20:681–7.

    Article  CAS  PubMed  Google Scholar 

  13. Abdullah-Koolmees H, van Keulen AM, Nijenhuis M, Deneer VHM. Pharmacogenetics guidelines: overview and comparison of the DPWG, CPIC, CPNDS, and RNPGx guidelines. Front Pharm. 2021;11:595219.

    Article  Google Scholar 

  14. Whirl‐Carrillo M, Huddart R, Gong L, Sangkuhl K, Thorn CF, Whaley R, et al. An evidence‐based framework for evaluating pharmacogenomics knowledge for personalized medicine. Clin Pharm Ther. 2021;110:563–72.

    Article  Google Scholar 

Download references

Author information

Author notes

  1. These authors contributed equally: Yolande Saab, Zahi Nakad.

Authors and Affiliations

  1. Pharmaceutical Sciences Department, School of Pharmacy, Lebanese American University, Byblos, Lebanon

    Yolande Saab

  2. Electrical and Computer Engineering Department, School of Engineering, Lebanese American University, Byblos, Lebanon

    Zahi Nakad

Authors
  1. Yolande Saab
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zahi Nakad
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Both authors contributed equally to the conceptualization and design of the study, modeling of response, critical analysis, and write up.

Corresponding authors

Correspondence to Yolande Saab or Zahi Nakad.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Saab, Y., Nakad, Z. A software tool to adjust codeine dose based on CYP2D6 gene-pair polymorphisms and drug-drug interactions. Pharmacogenomics J 23, 217–224 (2023). https://doi.org/10.1038/s41397-023-00318-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41397-023-00318-7

Search

Advanced search

Quick links