Omeprazole

Proton pump inhibitors

ATC code: A02BC01 (Omeprazole)

Brand names

Prilosec, Zegerid

Mechanism of action

Irreversibly inhibits the H+/K+-ATPase in gastric parietal cells — the final step of gastric acid secretion. Converted to its active form in the acidic environment of parietal cell canaliculi, where it binds the enzyme covalently. The effect persists until new H+/K+-ATPase molecules are synthesized (about 24 hours).

Indications

Gastroesophageal reflux disease

First line

PPIs are first-line for GERD in adults per ACG 2022 and NICE CG184. Standard dose: omeprazole 20 mg once daily for 4–8 weeks in non-erosive disease, 40 mg in erosive disease. If the response is inadequate, assess adherence, timing, functional heartburn, and alternative diagnoses. Long-term maintenance uses the lowest effective dose.

Sources

Helicobacter pylori infection

First line

A component of H. pylori eradication regimens per Maastricht VI/Florence Consensus 2022. In triple therapy: omeprazole 20 mg BID with amoxicillin and clarithromycin. In bismuth quadruple therapy: with tetracycline and metronidazole. Course duration 14 days. PPI is continued at least 4 more weeks after antibiotics for mucosal healing.

Sources

Maastricht VI/Florence Consensus: Maastricht VI/Florence Consensus Report on the Management of Helicobacter pylori Infection (2022)

NSAID gastropathy prophylaxis

First line

Gastroprotection is indicated in long-term NSAID users with risk factors: age over 65, prior peptic ulcer or GI bleeding, concomitant anticoagulants, antiplatelet drugs, or glucocorticoids, and high NSAID doses. Routine gastroprotection in low-risk patients is not recommended.

Sources

ACG: ACG Clinical Guideline: Diagnosis and Management of Gastroesophageal Reflux Disease (2022)

Peptic ulcer disease

First line

Standard therapy for peptic ulcer disease: omeprazole 20–40 mg once or twice daily for 4–8 weeks depending on ulcer location. In H. pylori-positive patients, as part of an eradication regimen. Maintenance therapy is used in recurrent ulcers, H. pylori-negative ulcers, and chronic NSAID users.

Sources

Practical notes

Timing and administration

Take 30–60 minutes before the first meal. This is a fundamental rule: PPIs only bind active H+/K+-ATPase molecules, and the enzyme activates with the first food intake. Taking it after a meal or on an empty stomach without food markedly reduces efficacy. Swallow the capsule whole (the enteric coating protects the drug from acid inactivation).

Monitoring

On long-term therapy (over 1 year), check serum magnesium yearly, especially in patients on diuretics or digoxin. Check vitamin B12 in patients over 60 on long-term PPI therapy. Assess bone mineral density in postmenopausal women after 5 years of therapy. Long-term therapy requires periodic re-evaluation of indications.

Special situations

After long-term use (over 3 months) and abrupt discontinuation, rebound hyperacidity can occur — heartburn symptoms return from transient hyperacidity. Gradual taper is preferred with transition to the lowest effective dose, every other day, then H2 blockers as needed. Co-administration with clopidogrel: omeprazole and esomeprazole inhibit CYP2C19 more strongly than other PPIs and may reduce clopidogrel activation — pantoprazole or rabeprazole are preferred.

Common myths

Myth: 'PPIs are harmless and can be taken for years without monitoring'. Fact: long-term use is associated with hypomagnesemia, vitamin B12 deficiency, increased fracture risk, acute interstitial nephritis, C. difficile infection, and community-acquired pneumonia. Prescribing should be justified and periodically reviewed. Myth: 'heartburn requires lifelong treatment'. Fact: many patients do well with lifestyle changes (weight, meals, sleep position) and a short PPI course. Lifelong therapy is justified in severe erosive esophagitis, Barrett esophagus, or Zollinger-Ellison syndrome.

Safety

Contraindications

Hypersensitivity to any component
Concomitant use with rilpivirine and nelfinavir

Serious adverse effects

Hypomagnesemia with long-term use
Vitamin B12 deficiency
Acute interstitial nephritis
C. difficile-associated pseudomembranous colitis
Increased risk of hip, wrist, and spine fractures with long-term therapy

Common adverse effects

Headache
Diarrhea or constipation
Nausea, flatulence
Abdominal pain

Uncommon adverse effects

Transaminase elevation
Insomnia, dizziness
Paresthesia
Pruritus, rash

PregnancyFDA C

FDA category C. Large cohort studies have not shown a significant increase in birth defects. Used when clinically necessary and benefits outweigh risks.

Breastfeeding

Passes into milk in minimal amounts. Considered compatible with breastfeeding in infants over 1 month old.