Omeprazole (Dosage)

Omeprazole is a drug used in the treatment of dyspepsia, peptic ulcer and gastroesophageal reflux disease. It belongs to the group of proton pump inhibitors thus causing acid depletion of gastric mucosal cells. The presence of certain polymorphisms in the CYP2C19 gene, involved in its metabolism, can cause important variations in the efficacy of this treatment.

Omeprazole is an inhibitor of the proton pump (PPI). It belongs to a group of compounds that inhibit the enzyme adenosine triphosphatase H+/K+ (proton pump), which is the final common route of acid production by gastric parietal cells. These compounds are the most potent inhibitors of acid secretion.

CONTRAINDICATIONS

Hypersensitivity to omeprazole (or to other proton pump inhibitors such as lansoprazole, pantoprazole, esomeprazole, rabeprazole).

CAUTIONS

Hyperplasia of the parietal cells has been observed during the use of omeprazole, also fundic glandular polyps and hyperplasia of the enterochromaffin-like cells as a consequence of acid suppression and hypergastrinemia have appeared in some cases.

An increase in the risk of developing gastroenteritis or pneumonia acquired in the community as a consequence of hypochlorhydria has been described.

The withdrawal of omeprazole should be slow (within a month) to avoid the rebound of acid secretion that would lead to the recurrence of symptoms.

At high doses and in prolonged treatment, the risk of fracture of the hip, wrist and spine increases, especially in the elderly or in the presence of other risk factors. It is important to ensure the intake of calcium and vitamin D during treatment if there is a risk of osteoporosis.

There is a risk of subacute cutaneous lupus erythematosus (SCLE) if injuries occur, especially in areas of the skin exposed to the sun, accompanied by arthralgia. In these cases interrupt the treatment with omeprazole.

SIDE EFFECTS

Headache, diarrhea, constipation, abdominal pain, nausea/vomiting and flatulence.

PHARMACOLOGIC INTERACTIONS

Omeprazole reduces the absorption of: ketoconazole, itraconazole, posaconazole and erlotinib (avoid concomitance with posaconazole and erlotinib).

Omeprazole increases the systemic exposure of active substances metabolized by CYP2C19.

Concomitant administration of omeprazole and clopidogrel is not recommended as the transformation of clopidogrel into its active metabolite is reduced, reducing the anticoagulant efficacy. In patients on treatment with clopidogrel who require treatment with anti-ulcers, it is recommended to replace ompeprazole with other drugs with a lower profile of interactions (for example pantoprazole or lansoprazole).

It can also cause a lower elevation in the plasma levels of other drugs metabolized by the CYP system, the most important being diazepam, warfarin, phenytoin and carbamazepine.

Omeprazole increases the serum concentration of tacrolimus (monitor concentration and renal function, adjust tacrolimus dose if necessary), methotrexate (temporarily withdraw treatment with omeprazole) and saquinavir.

Omeprazole interferes with neuroendocrine tumors tests (suspend treatment 5 days before the tests).

The combination of omeprazole with clopidogrel or atazanavir is not recommended (if necessary, monitor and increase atazanavir dose to 400 mg + 100 mg ritonavir).

BRAND NAMES

  • Arapride ®
  • Audazol ®
  • Aulcer ®
  • Belmazol ®
  • Ceprandal ®
  • Dolintol ®
  • Emeproton ®
  • Gastrimut ®
  • Losec ®
  • Miol ®
  • Norpramin ®
  • Novek
  • Nuclosina ®
  • Omapren ®
  • Ompranyt ®
  • Parizac ®
  • Pepticum ®
  • Prysma ®
  • Ulceral ®
  • Ulcesep ®
  • Zimor ®

Genes analyzed

CYP2C19

Bibliography

Chiba K, Shimizu K, Kato M, et al.Prediction of inter-individual variability in the pharmacokinetics of CYP2C19 substrates in humans. Drug Metab Pharmacokinet. 2014;29(5):379-86.

El Rouby N, Lima JJ, Johnson JA.Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine. Expert Opin Drug Metab Toxicol. 2018 Apr;14(4):447-460.

Lima JJ, Thomas CD, Barbarino J, et al.Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing. Clin Pharmacol Ther. 2021 Jun;109(6):1417-1423.

Zhao F, Wang J, Yang Y, et al.Effect of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple therapy for Helicobacter pylori eradication: a meta-analysis. Helicobacter. 2008 Dec;13(6):532-41.

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