Evidence map›Paper›PMID 40916919›Full record

ArticlePharmacotherapy2025

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

Eugene Jeong, Aditi Shendre, Yu Su, Xingyi Guo, Lang Li, You Chen

Abstract read
In one paragraph

Article in Pharmacotherapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Eugene JeongDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.ORCID 0000-0001-8240-1198
Aditi ShendreDepartment of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, Ohio, USA.ORCID 0000-0003-4123-7613
Yu SuDepartment of Computer Science and Engineering, College of Engineering, The Ohio State University, Columbus, Ohio, USA.ORCID 0000-0002-6649-4766
Xingyi GuoDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.ORCID 0000-0001-5269-1294
Lang LiDepartment of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, Ohio, USA.ORCID 0000-0002-0746-1809
You ChenDepartment of Biomedical Informatics, School of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.ORCID 0000-0001-8232-8840

Funding

Vanderbilt Institute for Clinical and Translational Research (VICTR) -Identifying correlates of functional immunity in SARS-CoV-2 convalescent plasmaUL1TR002243 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Paul A. Harris, Wesley H Self · 2017 to 2026
$130.7M
Vanderbilt Training Program in Molecular and Genetic Epidemiology of CancerT32CA160056 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Xiao-Ou Shu · 2017 to 2026
$3.8M
Machine learning drives translational research from drug interactions to pharmacogeneticsR01LM014199 · NLM · OHIO STATE UNIVERSITY · PI You Chen, Lang Li · 2023 to 2026
$2.5M
National Cancer Institute of the National Institutes of Health T32CA160056National Center for Advancing Translational Sciences of the National Institutes of Health UL1TR002243NCATS NIH HHS UL1 TR002243NCI NIH HHS T32 CA160056NLM NIH HHS R01 LM014199U.S. National Library of Medicine of the National Institutes of Health R01LM014199
6 · The paper itself

Abstract

backgroundOmeprazole, a widely used proton pump inhibitor, has been associated with rare but serious adverse events such as myopathy. Previous research suggests that concurrent use of omeprazole with fluconazole, a potent cytochrome P450 (CYP) 2C19/3A4 inhibitor, may increase the risk of myopathy. However, the contribution of genetic polymorphisms in CYP enzymes remains unclear.

aimsThis study leveraged electronic health record (EHR) and biobank data to validate an interaction between omeprazole and fluconazole and to explore drug-gene interactions (DGIs) between omeprazole and polymorphisms in CYP enzymes. MATERIALS AND

methodsA nested case-control design with incidence-density matching was used. Cases were defined as patients who developed myopathy during ongoing omeprazole therapy. For each case, up to four controls were selected from patients who had not developed myopathy by the time the case was diagnosed. Conditional logistic regression models, adjusting for relevant covariates, evaluated (i) the association between concomitant fluconazole use and myopathy and (ii) genotype-stratified myopathy risk.

resultsAmong 902 cases and 3608 controls, the combined use of omeprazole and fluconazole was linked to an increased risk of myopathy (adjusted odds ratio [AOR] = 1.75, 95% confidence interval [CI]: 1.17-2.63, p = 0.007). In the DGI analysis, which included 862 cases and 3448 controls, individuals classified as CYP2C19 poor metabolizers paired with CYP3A4 extensive metabolizers showed a significantly higher myopathy risk (AOR = 1.62, 95% CI: 1.03-2.55, p = 0.036); those with CYP2C19 poor metabolizer/CYP3A4 intermediate metabolizer had an even greater risk (AOR = 4.77, 95% CI: 1.74-13.1, p = 0.002). DISCUSSION: These findings not only confirm previously reported drug-drug interactions (DDIs) between omeprazole and fluconazole but also reveal the emerging clinical implications of DGIs.

conclusionBy integrating EHR and genetic data, the study showcases how informatics tools can translate DDI findings into DGI hypotheses, effectively bridging genetic insights and clinical outcomes.

Indexed as

Cytochrome P-450 CYP2C19Cytochrome P-450 CYP3AFluconazoleMuscular DiseasesOmeprazoleProton Pump InhibitorsAdultAgedCase-Control StudiesDrug InteractionsFemaleGenotypeHumansMaleMiddle AgedCYP2C19 protein, humanCYP3A4 protein, humanCytochrome P-450 CYP2C19Cytochrome P-450 CYP3AFluconazoleOmeprazoleProton Pump Inhibitorsbiobankdrug interactionsEHRomeprazolepharmacogenomicspharmacokineticstranslational science

Identifiers

PMID40916919
PMCPMC12530008

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.