OMEPRAZOLE CAP,EC

Clinical Criteria Summary

Clopidogrel is a prodrug requiring biotransformation to its active metabolite via the hepatic cytochrome P450 (CYP) 2C19 enzyme.
Omeprazole and other proton pump inhibitors (PPIs) utilize the same CYP450 metabolic pathway, theoretically causing competitive inhibition and decreased concentration of the active clopidogrel moiety.

PPI therapy is indicated for patients receiving any antithrombotic regimen who are at high risk of gastrointestinal bleeding.
PPIs reduce the risk of upper gastroduodenal bleeding in patients treated with antiplatelet agents.
For patients with GERD on clopidogrel presenting with LA grade C or D esophagitis or uncontrolled GERD symptoms, established benefits of PPI treatment outweigh proposed cardiovascular risks.

Concomitant use of omeprazole and clopidogrel does not demonstrate significant adverse cardiovascular effects; no significant differences in MACE, MI, or all-cause death are observed in randomized controlled trials and propensity score-matched studies.
No interaction has been observed between PPIs and aspirin, prasugrel, or ticagrelor.

Deprescribe PPIs as much as possible per established de-prescribing guidelines.
Do not limit omeprazole use in patients on clopidogrel due to the lack of demonstrated adverse cardiovascular effects.

Helicobacter pylori (H. pylori) infection
Treatment-naïve patients
Treatment-experienced patients with persistent H. pylori despite treatment with optimized bismuth quadruple therapy or vonoprazan dual therapy

Suggested as a first-line alternative treatment option for treatment-naïve patients when optimized bismuth quadruple therapy cannot be used
Suggested as a salvage regimen for treatment-experienced patients with persistent H. pylori; supported by substantial data for rifabutin triple therapy given as individual components for salvage in patients with multiple treatment failures
Can be administered without the need for susceptibility testing (the only other regimen besides optimized bismuth quadruple therapy that does not require susceptibility testing)
Supported for use when optimized bismuth quadruple therapy and vonoprazan dual therapy cannot be used or have failed
Note: The co-formulated combination product has not been studied in treatment-experienced patients; however, the 2024 ACG guidelines suggest it as an alternative to individual components to potentially maximize pharmacokinetics and lower the risk of myelotoxicity

Co-formulated in a delayed release capsule containing omeprazole, rifabutin, and amoxicillin
Administer 4 capsules TID with food
Provides daily doses of 120 mg omeprazole, 150 mg rifabutin, and 2-3 g/day amoxicillin

Rifabutin is a known CYP3A4 substrate and inducer; omeprazole inhibits CYP2C19
Patients must be evaluated for drug-drug interactions prior to prescribing (e.g., azole antifungals, antiretrovirals, warfarin, methotrexate, cyclosporine, tacrolimus)