Drug/Small Molecule:
esomeprazole

last updated 08/10/2011

Dutch Pharmacogenetics Working Group Guideline for esomeprazole and CYP2C19

Summary

For CYP2C19 ultrarapid metabolizers, be extra alert to insufficient response and consider increasing esomeprazole dose by 50-100%.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for esomeprazole based on CYP2C19 genotype. For the CYP2C19 UM phenotype, they conclude to be extra alert to insufficient response and recommend to consider dose increase by 50-100%.

Phenotype (Genotype) Therapeutic Dose Recommendation Level of Evidence Clinical Relevance
CYP2C19 PM (*2/*2, *2/*3, *3/*3) None Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints Positive clinical effects
CYP2C19 IM (*1/*2, *1/*3, *17/*2, *17/*3) None Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints Positive clinical effects
CYP2C19 UM (*17/*17) Helicobacter pylori eradication: increase dose by 50-100%. Be extra alert to insufficient response
Other: be extra alert to insufficient response. Consider dose increase by 50-100%
no data was retrieved with the literature search no data was retrieved with the literature search

PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.



last updated 10/25/2013

FDA Label for esomeprazole and CYP2C19

This label is on the FDA Biomarker List
Actionable PGx

Summary

The FDA-approved drug label for esomeprazole (NEXIUM) notes that individuals who are CYP2C19 poor metabolizers may have double the steady state area under the plasma concentration-time curve (AUC) of esomeprazole compared to extensive metabolizers.

Annotation

Esomeprazole (NEXIUM) is a proton pump inhibitor and entantiomer of omeprazole, and is metabolized in the liver by CYP2C19 and CYP3A4. The FDA-approved drug label for esomeprazole states that CYP2C19 poor metabolizers have an esomeprazole steady state AUC double that of extensive metabolizers.

Excerpt from the esomeprazole (NEXIUM) drug label:

CYP2C19 isoenzyme exhibits polymorphism in the metabolism of esomeprazole...At steady state, the ratio of AUC in Poor Metabolizers to AUC in the rest of the population (Extensive Metabolizers) is approximately 2.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the esomeprazole drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Gastroesophageal Reflux
    • Indications & usage section, Adverse reactions section
    • source: PHONT
  • Peptic Ulcer
    • Indications & usage section, Warnings section, Adverse reactions section
    • source: PHONT
  • CYP1A2
    • Drug interactions section
    • source: FDA Label
  • CYP2A6
    • Drug interactions section
    • source: FDA Label
  • CYP2C19
    • Drug interactions section, Clinical pharmacology section, dosage, metabolism/PK
    • source: FDA Label
  • CYP2C9
    • Drug interactions section
    • source: FDA Label
  • CYP2D6
    • Drug interactions section
    • source: FDA Label
  • CYP2E1
    • Drug interactions section
    • source: FDA Label
  • CYP3A4
    • Drug interactions section, metabolism/PK
    • source: FDA Label

last updated 05/08/2014

European Medicines Agency (EMA) Label for esomeprazole and CYP2C19

Informative PGx

Summary

The EMA European Public Assessment Report (EPAR) for esomeprazole (Nexium Control) notes that CYP2C19 poor metabolizers have higher plasma concentrations of the drug compared to extensive metabolizers, but there are no implications for dosing.

Annotation

Esomeprazole is metabolized by CYP2C19 and CYP3A4, and concomitant use of drugs that inhibit these enzymes may affect esomeprazole metabolism. CYP2C19 poor metabolizers have higher plasma concentrations of esomeprazole as compared to extensive metabolizers.

Excerpt/s from the esomeprazole (Nexium Control) EPAR:

Poor metabolisers
Approximately 2.9±1.5% of the population lack a functional CYP2C19 enzyme and are called poor metabolisers. In these individuals the metabolism of esomeprazole is probably mainly catalysed by CYP3A4. After repeated once-daily administration of 40 mg esomeprazole, the mean area under the plasma concentration-time curve was approximately 100% higher in poor metabolisers than in subjects having a functional CYP2C19 enzyme (extensive metabolisers). Mean peak plasma concentrations were 60% higher. These findings have no implications for the posology of esomeprazole.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the esomeprazole (Nexium Control) EMA drug label.

*Disclaimer: The contents of this page have not been endorsed by the EMA and are the sole responsibility of PharmGKB.

Genes and/or phenotypes found in this label

  • Gastroesophageal Reflux
    • Indications & usage section, Information for patients section, Pharmacodynamics section, other
    • source: European Medicines Agency (EMA) Label
  • CYP2C19
    • Drug interactions section, Pharmacokinetics section, Warnings and precautions section, metabolism/PK
    • source: European Medicines Agency (EMA) Label
  • CYP3A4
    • Drug interactions section, Pharmacokinetics section, metabolism/PK
    • source: European Medicines Agency (EMA) Label

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?
Roche AmpliChip CYP450 Test Variant in CYP2C19
Luminex xTAG CYP2C19 CYP2C19*1, CYP2C19*10, CYP2C19*17, CYP2C19*2, CYP2C19*3, CYP2C19*4, CYP2C19*5, CYP2C19*6, CYP2C19*7, CYP2C19*8, CYP2C19*9

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA CYP2C19 *1 N/A N/A N/A
No VIP available No VIP available VA CYP2C19 *1A N/A N/A N/A
No VIP available CA VA CYP2C19 *2 N/A N/A N/A
No VIP available CA VA CYP2C19 *3 N/A N/A N/A
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • (-)-omeprazole
  • (s)-omeprazole
  • Esomeprazole Sodium
  • Esomperazole
  • esomeprazole
Trade Names
  • Axagon
  • Esopral
  • Lucen
  • Nexiam
  • Nexium
  • Nexium Control
  • Nexium IV
Brand Mixture Names

PharmGKB Accession Id:
PA10075

Description

A highly effective inhibitor of gastric acid secretion used in the therapy of stomach ulcers and zollinger-ellison syndrome. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-exchanging ATPase) in the proton pump of gastric parietal cells.

Source: Drug Bank

Indication

For the treatment of acid-reflux disorders (GERD), peptic ulcer disease, H. pylori eradication, and prevention of gastroinetestinal bleeds with NSAID use.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H +/K +-ATPase in the gastric parietal cell. By acting specifically on the proton pump, Esomeprazole blocks the final step in acid production, thus reducing gastric acidity.

Source: Drug Bank

Pharmacology

Esomeprazole is a compound that inhibits gastric acid secretion and is indicated in the treatment of gastroesophageal reflux disease (GERD), the healing of erosive esophagitis, and H. pylori eradication to reduce the risk of duodenal ulcer recurrence. Esomeprazole belongs to a new class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or H2 histamine antagonistic properties, but that suppress gastric acid secretion by specific inhibition of the H +/K + ATPase at the secretory surface of the gastric parietal cell. By doing so, it inhibits acid secretion into the gsatric lumen. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.

Source: Drug Bank

Food Interaction

Take without regard to meals.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Mainly hepatic. Esomeprazole is completely metabolized by the cytochrome P450 system via CYP2C19 and CYP3A4. Metabolism produces inactive hydroxy and desmethyl metabolites, which have no effect on gastric acid secretion. Less than 1% of the parent drug is excreted in urine.

Source: Drug Bank

Protein Binding

97%

Source: Drug Bank

Absorption

90%

Source: Drug Bank

Half-Life

1-1.5 hours

Source: Drug Bank

Toxicity

Blurred vision, confusion, drowsiness, dry mouth, flushing headache, nausea, rapid heartbeat, sweating

Source: Drug Bank

Route of Elimination

Approximately 80% of the administered dose of esomeprazole is excreted as metabolites in urine and the remaining 20% is excreted in feces.

Source: Drug Bank

Volume of Distribution

Source: Drug Bank

Chemical Properties

Chemical Formula

C17H19N3O3S

Source: Drug Bank

Isomeric SMILES

Cc1cnc(c(c1OC)C)C[S@](=O)c2[nH]c3ccc(cc3n2)OC

Source: OpenEye

Canonical SMILES

COC1=CC2=C(NC(=N2)[S@](=O)CC2=NC=C(C)C(OC)=C2C)C=C1

Source: Drug Bank

Average Molecular Weight

345.416

Source: Drug Bank

Monoisotopic Molecular Weight

345.114712179

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
ATP12A (source: Drug Bank)
ATP1A1 (source: Drug Bank)
ATP4A (source: Drug Bank)

Drug Interactions

Drug Description
esomeprazole This gastric pH modifier decreases the levels/effects of atazanavir (source: Drug Bank)
esomeprazole This gastric pH modifier decreases the levels/effects of atazanavir (source: Drug Bank)
atazanavir This gastric pH modifier decreases the levels/effects of atazanavir (source: Drug Bank)
atazanavir This gastric pH modifier decreases the levels/effects of atazanavir (source: Drug Bank)
enoxacin The agent decreases the absorption of enoxacin (source: Drug Bank)
enoxacin Esomeprazole may decrease the absorption of enoxacin. (source: Drug Bank)
indinavir Omeprazole decreases the absorption of indinavir (source: Drug Bank)
indinavir Omeprazole decreases the absorption of indinavir (source: Drug Bank)
itraconazole The proton pump inhibitor decreases the absorption of imidazole (source: Drug Bank)
itraconazole The proton pump inhibitor decreases the absorption of imidazole (source: Drug Bank)
ketoconazole The proton pump inhibitor decreases the absorption of imidazole (source: Drug Bank)
ketoconazole The proton pump inhibitor decreases the absorption of imidazole (source: Drug Bank)
esomeprazole Omeprazole decreases the absorption of indinavir (source: Drug Bank)
esomeprazole Omeprazole decreases the absorption of indinavir (source: Drug Bank)
esomeprazole The proton pump inhibitor decreases the absorption of imidazole (source: Drug Bank)
esomeprazole The proton pump inhibitor decreases the absorption of imidazole (source: Drug Bank)
esomeprazole The proton pump inhibitor decreases the absorption of imidazole (source: Drug Bank)
esomeprazole The proton pump inhibitor decreases the absorption of imidazole (source: Drug Bank)
esomeprazole Tipranavir, co-administered with Ritonavir, may decrease the plasma concentration of Esomeprazole. Consider alternate therapy or increase the dose of Esomeprazole based on the therapeutic response. (source: Drug Bank)

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to esomeprazole: 16

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Effects of CYP2C19 loss-of-function variants on the eradication of H. pylori infection in patients treated with proton pump inhibitor-based triple therapy regimens: a meta-analysis of randomized clinical trials. PloS one. 2013. Tang Hui-Lin, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
A comparison of the acid-inhibitory effects of esomeprazole and rabeprazole in relation to pharmacokinetics and CYP2C19 polymorphism. Alimentary pharmacology & therapeutics. 2012. Hunfeld N G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Efficacy and tolerability of first-line triple therapy with levofloxacin and amoxicillin plus esomeprazole or rabeprazole for the eradication of Helicobacter pylori infection and the effect of CYP2C19 genotype: a 1-week, randomized, open-label study in Chinese adults. Clinical therapeutics. 2010. Pan Xiaolin, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
A comparison of the acid-inhibitory effects of esomeprazole and pantoprazole in relation to pharmacokinetics and CYP2C19 polymorphism. Alimentary pharmacology & therapeutics. 2010. Hunfeld N G, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Optimal dose regimens of esomeprazole for gastric acid suppression with minimal influence of the CYP2C19 polymorphism. European journal of clinical pharmacology. 2009. Lou Horng-Yuan, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ADME pharmacogenetics: current practices and future outlook. Expert opinion on drug metabolism & toxicology. 2009. Grossman Iris. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Analytical and bioanalytical chemistry. 2008. Zanger Ulrich M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Proton pump inhibitors: an update of their clinical use and pharmacokinetics. European journal of clinical pharmacology. 2008. Shi Shaojun, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Effect of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple therapy for Helicobacter pylori eradication: a meta-analysis. Helicobacter. 2008. Zhao Fujun, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Effect of the CYP2C19 polymorphism on the eradication rate of Helicobacter pylori infection by 7-day triple therapy with regular proton pump inhibitor dosage. Journal of gastroenterology and hepatology. 2008. Kang Jung Mook, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinical impact of CYP2C19 polymorphism on the action of proton pump inhibitors: a review of a special problem. International journal of clinical pharmacology and therapeutics. 2006. Klotz U. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Esomeprazole-induced healing of gastroesophageal reflux disease is unrelated to the genotype of CYP2C19: evidence from clinical and pharmacokinetic data. Clinical pharmacology and therapeutics. 2005. Schwab Matthias, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein. Naunyn-Schmiedeberg's archives of pharmacology. 2001. Pauli-Magnus C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The proton-pump inhibitors: similarities and differences. Clinical therapeutics. 2000. Horn J. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0186-6020-01
DrugBank:
DB00736
ChEBI:
50275
KEGG Drug:
D01984
PubChem Compound:
4594
PubChem Substance:
3865629
Drugs Product Database (DPD):
2244521
Therapeutic Targets Database:
DCL000524
FDA Drug Label at DailyMed:
c325bbfc-46f3-471e-7bbc-ed0d6965d13b

Clinical Trials

These are trials that mention esomeprazole and are related to either pharmacogenetics or pharmacogenomics.

Common Searches

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.