Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing

John J Lima¹, Cameron D Thomas², Julia Barbarino³, Zeruesenay Desta⁴, Sara L Van Driest⁵, Nihal El Rouby^{2

6}, Julie A Johnson², Larisa H Cavallari², Valentina Shakhnovich^{7

8

9}, David L Thacker^{10

11}, Stuart A Scott^{12

13}, Matthias Schwab^{14

15

16}, Chakradhara Rao S Uppugunduri^{17

18}, Christine M Formea¹⁹, James P Franciosi^{20

21}, Katrin Sangkuhl³, Andrea Gaedigk⁷, Teri E Klein³, Roseann S Gammal^{22

23}, Takahisa Furuta²⁴

Affiliations

¹ Center for Pharmacogenomics and Translational Research, Nemours Children's Health, Jacksonville, Florida, USA.
² Department of Pharmacotherapy and Translational Research, and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
³ Department of Biomedical Data Science, Stanford University, Stanford, California, USA.
⁴ Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁵ Departments of Pediatrics and Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
⁶ Division of Pharmacy Practice & Administrative Sciences, University of Cincinnati James Winkle College of Pharmacy, Cincinnati, Ohio, USA.
⁷ Division of Clinical Pharmacology, Toxicology, and Therapeutic Innovation, Children's Mercy Kansas City and University of Missouri Kansas City School of Medicine, Kansas City, Missouri, USA.
⁸ Division of Gastroenterology, Hepatology, and Nutrition, Children's Mercy Kansas City, Kansas City, Missouri, USA.
⁹ Center for Children's Healthy Lifestyles & Nutrition, Kansas City, Missouri, USA.
¹⁰ Department of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹¹ Translational Software, Bellevue, Washington, USA.
¹² Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹³ Sema4, Stamford, Connecticut, USA.
¹⁴ Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
¹⁵ Department of Clinical Pharmacology, University Hospital, Tuebingen, Germany.
¹⁶ Department of Pharmacy and Biochemistry, University of Tuebingen, Tuebingen, Germany.
¹⁷ CANSEARCH Research Laboratory, Department of Pediatrics, Gynecology, and Obstetrics, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
¹⁸ Oncology-Hematology Unit, Department of Pediatrics, Gynecology, and Obstetrics, Geneva University Hospital, Geneva, Switzerland.
¹⁹ Department of Pharmacy Services and Intermountain Precision Genomics, Intermountain Healthcare, Salt Lake City, Utah, USA.
²⁰ Division of Gastroenterology, Hepatology, and Nutrition, Nemours Children's Hospital, Orlando, Florida, USA.
²¹ Department of Pediatrics, University of Central Florida College of Medicine, Orlando, Florida, USA.
²² Department of Pharmacy Practice, MCPHS University School of Pharmacy, Boston, Massachusetts, USA.
²³ Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
²⁴ Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.

PMID: 32770672
PMCID: PMC7868475
DOI: 10.1002/cpt.2015

Practice Guideline

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing

John J Lima et al. Clin Pharmacol Ther. 2021 Jun.

. 2021 Jun;109(6):1417-1423.

doi: 10.1002/cpt.2015. Epub 2020 Sep 20.

Authors

Affiliations

¹ Center for Pharmacogenomics and Translational Research, Nemours Children's Health, Jacksonville, Florida, USA.
² Department of Pharmacotherapy and Translational Research, and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
³ Department of Biomedical Data Science, Stanford University, Stanford, California, USA.
⁴ Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁵ Departments of Pediatrics and Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
⁶ Division of Pharmacy Practice & Administrative Sciences, University of Cincinnati James Winkle College of Pharmacy, Cincinnati, Ohio, USA.
⁷ Division of Clinical Pharmacology, Toxicology, and Therapeutic Innovation, Children's Mercy Kansas City and University of Missouri Kansas City School of Medicine, Kansas City, Missouri, USA.
⁸ Division of Gastroenterology, Hepatology, and Nutrition, Children's Mercy Kansas City, Kansas City, Missouri, USA.
⁹ Center for Children's Healthy Lifestyles & Nutrition, Kansas City, Missouri, USA.
¹⁰ Department of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹¹ Translational Software, Bellevue, Washington, USA.
¹² Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹³ Sema4, Stamford, Connecticut, USA.
¹⁴ Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
¹⁵ Department of Clinical Pharmacology, University Hospital, Tuebingen, Germany.
¹⁶ Department of Pharmacy and Biochemistry, University of Tuebingen, Tuebingen, Germany.
¹⁷ CANSEARCH Research Laboratory, Department of Pediatrics, Gynecology, and Obstetrics, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
¹⁸ Oncology-Hematology Unit, Department of Pediatrics, Gynecology, and Obstetrics, Geneva University Hospital, Geneva, Switzerland.
¹⁹ Department of Pharmacy Services and Intermountain Precision Genomics, Intermountain Healthcare, Salt Lake City, Utah, USA.
²⁰ Division of Gastroenterology, Hepatology, and Nutrition, Nemours Children's Hospital, Orlando, Florida, USA.
²¹ Department of Pediatrics, University of Central Florida College of Medicine, Orlando, Florida, USA.
²² Department of Pharmacy Practice, MCPHS University School of Pharmacy, Boston, Massachusetts, USA.
²³ Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
²⁴ Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.

PMID: 32770672
PMCID: PMC7868475
DOI: 10.1002/cpt.2015

Abstract

Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, Helicobacter pylori infection, and pathological hypersecretory conditions. Most PPIs are metabolized primarily by cytochrome P450 2C19 (CYP2C19) into inactive metabolites, and CYP2C19 genotype has been linked to PPI exposure, efficacy, and adverse effects. We summarize the evidence from the literature and provide therapeutic recommendations for PPI prescribing based on CYP2C19 genotype (updates at www.cpicpgx.org). The potential benefits of using CYP2C19 genotype data to guide PPI therapy include (i) identifying patients with genotypes predictive of lower plasma exposure and prescribing them a higher dose that will increase the likelihood of efficacy, and (ii) identifying patients on chronic therapy with genotypes predictive of higher plasma exposure and prescribing them a decreased dose to minimize the risk of toxicity that is associated with long-term PPI use, particularly at higher plasma concentrations.

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Conflict of interest statement

Conflicts of Interest:

JAJ is a consultant to United Health Group for their plans to begin implementing pharmacogenomics in clinical practice; SAS is a paid employee of Sema4, which is a for-profit genetic testing company that offers pharmacogenetic testing. DLT is a paid employee of Translational Software, which is a for-profit genetic testing company that offers pharmacogenetic testing. All other authors declared no competing interests for this work. As an Associate Editor for Clinical Pharmacology & Therapeutics, Sara L. Van Driest was not involved in the review or decision process for this paper.

References

1. El Rouby N, Lima JJ & Johnson JA Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine. Expert Opin Drug Metab Toxicol 14, 447–60 (2018). - PMC - PubMed
1. Jaynes M & Kumar AB The risks of long-term use of proton pump inhibitors: a critical review. Ther Adv Drug Saf 10, 2042098618809927 (2019). doi: 10.1177/2042098618809927. - DOI - PMC - PubMed
1. CPIC. CPIC® Guideline for Proton Pump Inhibitors and CYP2C19. <https://cpicpgx.org/guidelines/cpic-guideline-for-proton-pump-inhibitors...> (2020).
1. PharmGKB. Gene-specific Information Tables for CYP2C19. <https://www.pharmgkb.org/page/cyp2c19RefMaterials>. Accessed Jan 20 2020.
1. Sibbing D et al. Isolated and interactive impact of common CYP2C19 genetic variants on the antiplatelet effect of chronic clopidogrel therapy. J Thromb Haemost 8, 1685–93 (2010). - PubMed

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Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing

Affiliations

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing

Authors

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Abstract

Conflict of interest statement

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