Omeprazole

Omeprazole is a substituted benzimidazole proton pump inhibitor (PPI). FDA-approved products include Prilosec delayed-release capsules and delayed-release oral suspension packets, generic delayed-release capsules, over-the-counter delayed-release tablets, and an immediate-release combination with sodium bicarbonate (Zegerid). Omeprazole is compounded into oral liquids pursuant to patient-specific prescriptions.

• Treatment of active duodenal ulcer and active benign gastric ulcer.
• Helicobacter pylori eradication to reduce duodenal ulcer recurrence, in combination with antibiotics.
• Treatment of symptomatic gastroesophageal reflux disease (GERD) and erosive esophagitis, and maintenance of healing of erosive esophagitis.
• Pathological hypersecretory conditions such as Zollinger-Ellison syndrome.
• Pediatric GERD and erosive esophagitis from 1 month (erosive esophagitis due to acid-mediated GERD) or 1 year of age, depending on indication.

Omeprazole is a prodrug that accumulates in the acidic canaliculi of gastric parietal cells, where it converts to a sulfenamide that covalently and irreversibly inhibits H+/K+-ATPase, the final step of acid secretion. It suppresses basal and stimulated acid secretion; acid secretion recovers as new pumps are synthesized.

Omeprazole is acid labile, so it is given in delayed-release forms or with sodium bicarbonate. Bioavailability is about 30 to 40% and rises with repeated dosing. It is about 95% protein bound and is metabolized by CYP2C19 and, to a lesser extent, CYP3A4; CYP2C19 poor metabolizers and Asian populations have higher exposure. Plasma half-life is 0.5 to 1 hour, but acid suppression lasts up to 72 hours. Metabolites are excreted mainly in urine.

• Hypersensitivity to omeprazole or other substituted benzimidazoles; reactions have included anaphylaxis, angioedema, bronchospasm, acute tubulointerstitial nephritis and urticaria.
• Coadministration with rilpivirine-containing products.

• Symptomatic response does not exclude gastric malignancy; consider additional evaluation in adults with suboptimal response or early relapse.
• Acute tubulointerstitial nephritis can occur at any time; stop omeprazole if it develops.
• Clostridioides difficile-associated diarrhea, bone fracture with high-dose or long-term use, hypomagnesemia (and associated hypocalcemia and hypokalemia), and vitamin B12 deficiency with long-term use.
• Cutaneous and systemic lupus erythematosus; severe cutaneous adverse reactions including Stevens-Johnson syndrome and DRESS.
• Fundic gland polyps with long-term use. Elevated chromogranin A can interfere with neuroendocrine tumor testing; stop the PPI at least 14 days before testing.

Avoid with clopidogrel (reduced conversion to its active metabolite through CYP2C19 inhibition), atazanavir and nelfinavir; contraindicated with rilpivirine. Omeprazole can raise levels of saquinavir, tacrolimus, citalopram (QT risk), cilostazol, phenytoin, diazepam, digoxin and high-dose methotrexate, may alter warfarin effect, and reduces mycophenolate mofetil exposure. It reduces absorption of drugs that need gastric acid, such as ketoconazole, itraconazole, iron salts, erlotinib and dasatinib. St. John's wort and rifampin lower omeprazole levels; voriconazole raises them.

Headache, abdominal pain, nausea, diarrhea, vomiting and flatulence are most common; respiratory infection, fever and rash occur in children. Long-term effects are listed under Warnings and Precautions.

Available data from observational studies have not shown an increased risk of major malformations or other adverse pregnancy outcomes with omeprazole. Omeprazole is present in human milk in small amounts; consider the benefits of breastfeeding with the mother's need for treatment.

Symptom response; magnesium at baseline and periodically with long-term use or with digoxin or diuretics; vitamin B12 with long-term use; renal function if nephritis is suspected; INR with warfarin; tacrolimus and methotrexate levels when coadministered.

• Prilosec (omeprazole) delayed-release capsules and delayed-release oral suspension Prescribing Information.
• Zegerid (omeprazole and sodium bicarbonate) Prescribing Information.