Introduction
Omeprazole is a proton pump inhibitor (PPI) that has been widely used in clinical practice since its approval in 1989. As the first member of the benzimidazole class of PPIs, it revolutionized the treatment of acid-related disorders by providing superior acid suppression compared to previous therapies like H2-receptor antagonists. Omeprazole remains a cornerstone therapy for various gastrointestinal conditions involving excessive acid production.
Mechanism of Action
Omeprazole exerts its pharmacological effects through irreversible inhibition of the hydrogen-potassium adenosine triphosphatase (H+/K+ ATPase) enzyme system at the secretory surface of gastric parietal cells. This enzyme is responsible for the final step of gastric acid secretion. Omeprazole is a prodrug that requires activation in the acidic environment of the parietal cell canaliculi, where it transforms into a sulfenamide intermediate. This active form forms covalent disulfide bonds with cysteine residues on the alpha subunit of the H+/K+ ATPase pump, effectively blocking acid secretion for up to 24-72 hours. The drug's effect is dose-dependent and results in profound suppression of both basal and stimulated acid secretion.
Indications
FDA-approved indications include:
- Treatment of active duodenal ulcer
- Treatment of active benign gastric ulcer
- Treatment of erosive esophagitis
- Maintenance of healing of erosive esophagitis
- Symptomatic gastroesophageal reflux disease (GERD)
- Pathological hypersecretory conditions (Zollinger-Ellison syndrome, multiple endocrine adenomas, systemic mastocytosis)
- Helicobacter pylori eradication (in combination with antibiotics)
- Risk reduction of upper gastrointestinal bleeding in critically ill patients
Dosage and Administration
Standard adult dosing:- GERD: 20 mg once daily for 4-8 weeks
- Erosive esophagitis: 20-40 mg once daily for 4-8 weeks
- Gastric ulcer: 40 mg once daily for 4-8 weeks
- Duodenal ulcer: 20 mg once daily for 4-8 weeks
- H. pylori eradication: 20 mg twice daily with amoxicillin and clarithromycin for 10-14 days
- Hypersecretory conditions: 60 mg once daily (may increase up to 120 mg three times daily)
- Hepatic impairment: Maximum 20 mg daily in severe impairment
- Renal impairment: No dosage adjustment required
- Geriatric patients: No dosage adjustment required
- Pediatric patients: 1-20 kg: 5-10 mg daily; >20 kg: 10-20 mg daily
- Should be taken before meals, typically 30-60 minutes before breakfast
- Capsules should be swallowed whole; not to be crushed or chewed
- For patients with difficulty swallowing, capsules can be opened and contents mixed with applesauce
Pharmacokinetics
Absorption: Rapidly absorbed from the gastrointestinal tract, but extensive first-pass metabolism results in approximately 30-40% bioavailability. Absorption may be decreased if taken with food. Distribution: Volume of distribution is approximately 0.3 L/kg. Protein binding is approximately 95%, primarily to albumin. Metabolism: Extensively metabolized in the liver via the cytochrome P450 system, primarily CYP2C19 and CYP3A4. Produces several metabolites including hydroxyomeprazole, omeprazole sulfone, and sulfide derivatives. Elimination: Primarily excreted in urine (77%) as metabolites, with the remainder in feces. Elimination half-life is approximately 0.5-1 hour, but the duration of acid suppression persists much longer due to irreversible binding to proton pumps.Contraindications
- Hypersensitivity to omeprazole, other proton pump inhibitors, or any component of the formulation
- Concomitant use with rilpivirine-containing products due to potential for reduced antiviral efficacy
- Use of immediate-release omeprazole in patients with hereditary fructose intolerance
Warnings and Precautions
Acute interstitial nephritis: May occur at any time during therapy; discontinue if suspected Clostridium difficile-associated diarrhea: PPI use may increase risk Bone fracture: Long-term, high-dose therapy associated with increased risk of hip, wrist, and spine fractures Hypomagnesemia: Reported with prolonged PPI use; monitor magnesium levels before initiation and periodically during long-term therapy Cutaneous and systemic lupus erythematosus: New onset or exacerbation reported; discontinue if suspected Vitamin B12 deficiency: Long-term therapy may reduce vitamin B12 absorption Fundic gland polyps: Most common with long-term use, usually benign and reversible upon discontinuationDrug Interactions
CYP2C19 substrates: Omeprazole may increase concentrations of drugs metabolized by CYP2C19 (diazepam, citalopram, phenytoin, clopidogrel) CYP2C19 inhibitors: May increase omeprazole concentrations (fluvoxamine) CYP2C19 inducers: May decrease omeprazole concentrations (rifampin, St. John's wort) Drugs requiring gastric acidity for absorption: Reduced absorption of ketoconazole, iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil Methotrexate: May increase methotrexate levels Saquinavir: May decrease saquinavir levels Tacrolimus: May increase tacrolimus levels Warfarin: May increase INR and bleeding riskAdverse Effects
Common (≥1%):- Headache (7%)
- Abdominal pain (5%)
- Nausea (4%)
- Diarrhea (4%)
- Constipation (3%)
- Flatulence (3%)
- Dizziness (2%)
- Rash (2%)
- Acute interstitial nephritis
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Erythema multiforme
- Hepatitis
- Pancreatitis
- Hypomagnesemia
- Clostridium difficile-associated diarrhea
- Bone fracture
- Vitamin B12 deficiency
Monitoring Parameters
- Symptom improvement and resolution
- Renal function (especially with long-term use)
- Magnesium levels (with prolonged therapy or concomitant diuretic use)
- Vitamin B12 levels (with long-term therapy)
- Bone density (consider in patients on long-term, high-dose therapy)
- Liver function tests (periodically)
- Complete blood count (if clinical indication)
- Signs of gastrointestinal infection
- Signs of lupus erythematosus
Patient Education
- Take medication 30-60 minutes before breakfast for optimal effect
- Swallow capsules whole; do not crush or chew
- If unable to swallow capsule, may open and sprinkle contents on applesauce
- Report any signs of allergic reaction (rash, itching, swelling)
- Notify healthcare provider of any new or worsening symptoms
- Be aware that long-term use may increase risk of bone fractures, vitamin deficiencies, and certain infections
- Do not abruptly stop medication without consulting healthcare provider
- Inform all healthcare providers of omeprazole use, especially before starting new medications
- Regular follow-up appointments are important for monitoring therapy
- Report any unusual muscle spasms, seizures, or arrhythmias (possible signs of hypomagnesemia)
References
1. Shin JM, Kim N. Pharmacokinetics and pharmacodynamics of the proton pump inhibitors. J Neurogastroenterol Motil. 2013;19(1):25-35. 2. Strand DS, Kim D, Peura DA. 25 years of proton pump inhibitors: a comprehensive review. Gut Liver. 2017;11(1):27-37. 3. Omeprazole prescribing information. US Food and Drug Administration. 4. Savarino V, et al. Proton pump inhibitors: use and misuse in the clinical setting. Expert Rev Clin Pharmacol. 2018;11(11):1123-1134. 5. Freedberg DE, Kim LS, Yang YX. The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-715. 6. Moayyedi P, et al. ACG and CAG Clinical Guideline: Management of Dyspepsia. Am J Gastroenterol. 2017;112(7):988-1013. 7. Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108(3):308-328.