Association of Omeprazole-Related Myopathy With Drug-Drug and Drug-Gene Interactions Involving CYP2C19 and CYP3A4: A Nested Case-Control Study

  • 0Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

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Summary

This summary is machine-generated.

Concurrent use of omeprazole and fluconazole increases myopathy risk. Genetic variations in CYP enzymes, particularly CYP2C19 and CYP3A4, further elevate this risk, highlighting crucial drug-gene interactions.

Area Of Science

  • Pharmacogenomics
  • Clinical Pharmacology
  • Drug Safety

Background

  • Omeprazole, a proton pump inhibitor, is linked to myopathy.
  • Concurrent use with fluconazole, a CYP enzyme inhibitor, may heighten this risk.
  • The role of genetic variations in cytochrome P450 (CYP) enzymes is not fully understood.

Purpose Of The Study

  • Validate the drug-drug interaction (DDI) between omeprazole and fluconazole.
  • Investigate drug-gene interactions (DGIs) between omeprazole and CYP enzyme genetic polymorphisms.
  • Assess myopathy risk associated with these interactions using real-world data.

Main Methods

  • Nested case-control study design with incidence-density matching.
  • Utilized electronic health records (EHR) and biobank data.
  • Conditional logistic regression models analyzed DDI and DGI effects on myopathy risk.

Main Results

  • Combined omeprazole and fluconazole use significantly increased myopathy risk (AOR=1.75).
  • Specific CYP2C19 and CYP3A4 genetic profiles showed elevated myopathy risk (e.g., CYP2C19 poor metabolizers/CYP3A4 intermediate metabolizers: AOR=4.77).
  • Findings confirm DDIs and reveal significant DGIs.

Conclusions

  • Confirms the DDI between omeprazole and fluconazole regarding myopathy risk.
  • Highlights the significant clinical impact of DGIs involving CYP2C19 and CYP3A4.
  • Demonstrates the utility of integrating EHR and genetic data for DGI discovery.

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