2. Royal Dutch Pharmacists Association (KNMP). Dutch Pharmacogenetics Working Group (DPWG). Pharmacogenetic Guidelines [Internet]. Netherlands. Esomeprazole - CYP2C19 [Cited 2018]. Available from:
http://kennisbank.knmp.nl [Access is restricted to KNMP membership.]
This section contains excerpted
1
information on gene-based dosing recommendations. Neither this section nor other parts of this review contain the complete recommendations from the sources.
2018 Statement from the US Food and Drug Administration (FDA)
Metabolism
Esomeprazole is extensively metabolized in the liver by the cytochrome P450 (CYP) enzyme system. The metabolites of esomeprazole lack antisecretory activity. The major part of esomeprazole’s metabolism is dependent upon the CYP2C19 isoenzyme, which forms the hydroxy and desmethyl metabolites. The remaining amount is dependent on CYP3A4, which forms the sulphone metabolite. CYP2C19 isoenzyme exhibits polymorphism in the metabolism of esomeprazole, since some 3% of Caucasians and 15 to 20% of Asians lack CYP2C19 and are termed Poor Metabolizers. At steady state, the ratio of AUC in Poor Metabolizers to AUC in the rest of the population (Normal Metabolizers) is approximately 2.
[...]
Interaction with Clopidogrel
Avoid concomitant use of esomeprazole magnesium with clopidogrel. Clopidogrel is a prodrug. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by use with concomitant medications, such as esomeprazole, that inhibit CYP2C19 activity. Concomitant use of clopidogrel with 40 mg esomeprazole reduces the pharmacological activity of clopidogrel. When using esomeprazole magnesium consider alternative anti-platelet therapy.
Please review the complete therapeutic recommendations located here:
(1).
2018 Summary of recommendations from the Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy (KNMP)
CYP2C19 Poor Metabolizer (PM)
No action is needed for this gene-drug interaction.
Although the genetic variation leads to a higher plasma concentration of esomeprazole, there is insufficient evidence to support an effect on the therapeutic effectiveness and side effects.
CYP2C19 Intermediate Metabolizer (IM)
No action is needed for this gene-drug interaction.
Although the genetic variation leads to a higher plasma concentration of esomeprazole, there is insufficient evidence to support an effect on the therapeutic effectiveness and side effects.
CYP2C19 Ultrarapid Metabolizer (UM)
No action is required for this gene-drug interaction.
Although the genetic variation may lead to faster inactivation of esomeprazole, there is insufficient evidence to support an effect on the therapeutic effectiveness and side effects.
Background information
For more information about the PM, IM, and UM phenotypes: see the general background information about CYP2C19 on the KNMP Knowledge Bank or on www.knmp.nl (search for CYP2C19). Access requires KNMP membership.
Please review the complete therapeutic recommendations that are located here:
(2).
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The FDA labels specific drug formulations. We have substituted the generic names for any drug labels in this excerpt. The FDA may not have labeled all formulations containing the generic drug. Certain terms, genes and genetic variants may be corrected in accordance with nomenclature standards, where necessary. We have given the full name of abbreviations, shown in square brackets, where necessary.