Esomeprazole (brand name Nexium) is a proton pump inhibitor (PPI) used to treat gastroesophageal reflux disease (GERD) and to reduce the risk of gastric ulcers associated with nonsteroidal anti-inflammatory drug NSAID use. Esomeprazole is also used in the treatment of hypersecretory conditions, such as Zollinger-Ellison syndrome, and in combination with antibiotics to eradicate Helicobacter pylori (H. pylori) infection.
Esomeprazole reduces the acidity (raises the pH) in the stomach by inhibiting the secretion of gastric acid. The level of esomeprazole an individual is exposed to is influenced by several factors, such as the dose used and how quickly the drug is metabolized and inactivated.
Esomeprazole is primarily metabolized by the CYP2C19 enzyme. Individuals with increased CYP2C19 enzyme activity (“CYP2C19 ultrarapid metabolizers”) may have an insufficient response to standard doses of esomeprazole, because the drug is inactivated at a faster rate. In contrast, individuals who have reduced or absent CYP2C19 enzyme activity (i.e., CYP2C19 intermediate and poor metabolizers) have a greater exposure to esomeprazole.
The 2018 FDA-approved drug label for esomeprazole states that 3% of Caucasians, and 15–20% of Asians are CYP2C19 poor metabolizers, and that poor metabolizers have approximately twice the level of exposure to esomeprazole, compared with CYP2C19 normal metabolizers. However, the drug label does not include dosing recommendations for CYP2C19 poor metabolizers.
Esomeprazole recommendations have been published by the Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy (KNMP), which indicates that no change in dosing is recommended for CYP2C19 poor, intermediate, or ultrarapid metabolizers. The DPWG states that although genetic variation in CYP2C19 influences the plasma concentration of esomeprazole, there is insufficient evidence to support an effect on treatment outcomes or side effects. [from Medical Genetics Summaries]
- MedGen UID:
- 450454
- •Concept ID:
- CN077982
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- Sign or Symptom