Usage
Omeprazole is prescribed for the treatment of conditions involving excessive gastric acid secretion. These conditions include:
- Duodenal and Gastric Ulcers
- Gastroesophageal Reflux Disease (GERD)
- Erosive Esophagitis
- Zollinger-Ellison Syndrome (ZES)
- Helicobacter pylori infection (in combination with antibiotics)
- Stress Ulcer Prophylaxis in critically ill patients.
- Prevention of NSAID-associated ulcers.
Pharmacological Classification: Proton Pump Inhibitor (PPI)
Mechanism of Action: Omeprazole irreversibly inhibits the H+/K+-ATPase enzyme system (proton pump) in gastric parietal cells. This blocks the final step of acid production, effectively reducing gastric acid secretion.
Alternate Names
Omeprazole is the generic name. There are no internationally recognized alternate names for the drug itself, although it may be known by various names in different regions depending on local pharmaceutical regulations and naming conventions.
Brand Names: Prilosec, Losec, OmepraCare, Omeprazole Sandoz, Omeprazole (Teva). Several other generic versions also exist.
How It Works
Pharmacodynamics: Omeprazole suppresses gastric acid secretion by specifically targeting the proton pumps within the parietal cells of the gastric mucosa. This action results in a significant reduction in both basal and stimulated acid secretion.
Pharmacokinetics:
- Absorption: Omeprazole is rapidly absorbed after oral administration, reaching peak plasma concentrations within 0.5 to 3.5 hours. Administration should ideally be before a meal as food can decrease the rate but not the extent of absorption.
- Metabolism: Omeprazole is extensively metabolized in the liver by the cytochrome P450 (CYP) enzyme system, primarily CYP2C19 and CYP3A4. It is a prodrug that requires activation in the acidic canaliculi of the parietal cells to exert its effect.
- Elimination: Omeprazole metabolites are primarily excreted in the urine (about 80%) and feces (around 20%). It has an elimination half-life of approximately 0.5 to 3 hours, depending on the patient’s liver function and CYP2C19 metabolic status.
Mode of Action: Omeprazole, in its inactive form, crosses the parietal cell membrane and enters the secretory canaliculi, an acidic environment. Here, it transforms into its active, sulfenamide form. This active form binds covalently to cysteine residues within the H+/K+-ATPase enzyme, irreversibly inactivating it. This inhibits both basal and stimulated gastric acid secretion.
Receptor Binding/Enzyme Inhibition: Omeprazole acts via selective and irreversible inhibition of the H+/K+-ATPase enzyme, the final step in acid production. It does not directly interact with receptors or neurotransmitters.
Elimination Pathways: Primarily renal excretion with a smaller component of hepatic/biliary excretion via feces.
Dosage
Standard Dosage
Adults:
- Duodenal Ulcer: 20 mg orally once daily for 4-8 weeks.
- Gastric Ulcer: 40 mg orally once daily for 4-8 weeks.
- GERD: 20 mg orally once daily for 4-8 weeks. Maintenance therapy may be continued at 20 mg once daily for up to 1 year in patients with healed erosive esophagitis.
- Erosive Esophagitis: 20 mg orally once daily for 4-8 weeks. Maintenance therapy: 20 mg orally once daily.
- ZES: Initial dose of 60 mg orally once daily, adjustable up to 120 mg three times daily. Doses greater than 80 mg should be divided.
- H. pylori Infection: In combination with antibiotics; various regimens exist. An example: Omeprazole 20 mg twice daily for 10 days, Amoxicillin 1000 mg twice daily, and Clarithromycin 500 mg twice daily.
Children (1 year and older):
- GERD: Dose is weight-based, typically 0.7-1.4 mg/kg once daily.
- Erosive Esophagitis: Dose is weight-based, typically 0.7-1.4 mg/kg once daily.
Special Cases:
- Elderly Patients: No dose adjustment is generally required but may require lower doses with renal/hepatic dysfunction.
- Patients with Renal Impairment: No dose adjustment required.
- Patients with Hepatic Dysfunction: Dose reduction may be considered, starting with 10-20 mg daily. Close monitoring is advised.
- Patients with Comorbid Conditions: Consider individual patient factors, especially drug interactions and effects of other medications.
Clinical Use Cases
- Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: For prevention of stress ulcers, an intravenous dose of 40 mg once daily is usually recommended. High-risk patients may require higher doses (80mg bolus followed by 8mg/hr infusion) or prolonged duration of therapy.
- Emergency Situations (e.g., upper GI bleed): An initial intravenous loading dose of 40 mg followed by another 40 mg dose after 6-8 hours on the first day. After the first day: 40 mg once a day for up to 14 days.
Dosage Adjustments
- Consider dose reductions in patients with hepatic impairment.
- Renal impairment generally does not require dose adjustment.
- Genetic polymorphisms affecting CYP2C19 activity can influence omeprazole metabolism, therefore requiring dose adjustments in some cases.
Side Effects
Common Side Effects
Headache, diarrhea, abdominal pain, nausea, vomiting, flatulence, dizziness, upper respiratory infection.
Rare but Serious Side Effects
Severe allergic reactions (anaphylaxis, angioedema), Clostridium difficile-associated diarrhea, hypomagnesemia, bone fractures (with long-term use).
Long-Term Effects
Potential for vitamin B12 deficiency, hypomagnesemia, increased risk of certain infections (e.g., Clostridium difficile, pneumonia).
Adverse Drug Reactions (ADR)
Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), severe liver damage.
Contraindications
- Hypersensitivity to omeprazole or other substituted benzimidazoles.
- Concomitant administration with drugs metabolized by CYP2C19 when a narrow therapeutic window exists.
Drug Interactions
- CYP450 Interactions: Omeprazole is primarily metabolized by CYP2C19 and CYP3A4. It can inhibit the metabolism of drugs that are substrates of these enzymes, potentially increasing their serum levels.
- Drug-specific Interactions: Clopidogrel (reduced antiplatelet effect), Methotrexate (increased levels), Diazepam, Phenytoin (increased toxicity).
- Other Interactions: Ketoconazole, Itraconazole (decreased absorption), Warfarin (enhanced anticoagulant effect).
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Omeprazole is generally considered safe during pregnancy, although human data is limited. It’s best used only when the benefits outweigh the potential risks.
- Breastfeeding: Omeprazole is excreted in breast milk in small amounts. The benefits of breastfeeding generally outweigh the potential risk to the infant. However, monitoring for infant side effects is warranted.
Drug Profile Summary
- Mechanism of Action: Irreversible inhibition of the H+/K+-ATPase proton pump in gastric parietal cells, reducing gastric acid secretion.
- Side Effects: Headache, diarrhea, abdominal pain, nausea, vomiting. Rare but serious: C. difficile infection, hypomagnesemia.
- Contraindications: Hypersensitivity, concomitant use with certain medications.
- Drug Interactions: Clopidogrel, Methotrexate, Diazepam, Phenytoin, Ketoconazole, Itraconazole, Warfarin.
- Pregnancy & Breastfeeding: Generally considered safe, though data is limited.
- Dosage: Adults: 20-40 mg daily depending on indication. Children: weight-based dosing.
- Monitoring Parameters: Gastric pH, serum magnesium levels (with long-term use), signs of infection.
Popular Combinations
- Omeprazole + Amoxicillin + Clarithromycin (for H. pylori eradication).
Precautions
- General Precautions: Assess renal and hepatic function, consider potential drug interactions, rule out malignancy in patients with dyspepsia.
- Specific Populations: Use cautiously in patients with severe liver disease.
- Lifestyle Considerations: Advise patients to avoid alcohol and smoking, which can exacerbate gastric irritation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Omeprazole?
A: The dosage depends on the specific condition being treated. Adults: 20 mg daily for duodenal ulcer, GERD, and erosive esophagitis; 40 mg daily for gastric ulcer. Doses may be adjusted based on individual response and specific clinical situations. Pediatric dosing is weight-based.
Q2: How should Omeprazole be administered?
A: Orally, usually once a day before a meal. The capsules should be swallowed whole and not crushed or chewed.
Q3: Can Omeprazole be used during pregnancy?
A: Omeprazole is generally considered safe during pregnancy, but limited human data exists. Use only if the benefits outweigh potential risks.
Q4: What are the common side effects of Omeprazole?
A: Common side effects include headache, diarrhea, abdominal pain, nausea, and vomiting.
Q5: What are the potential drug interactions with Omeprazole?
A: Omeprazole can interact with several drugs, including Clopidogrel, Methotrexate, Diazepam, Phenytoin, and medications metabolized by CYP2C19 and CYP3A4.
Q6: Are there any long-term effects of Omeprazole use?
A: Long-term use may increase the risk of vitamin B12 deficiency, hypomagnesemia, and certain infections. Regular monitoring of serum magnesium levels is recommended with prolonged use.
Q7: How does Omeprazole affect patients with renal impairment?
A: Dose adjustment is generally not required for patients with renal impairment.
Q8: How does Omeprazole affect patients with hepatic impairment?
A: Dose reduction is recommended for patients with hepatic impairment. Close monitoring is advisable.
Q9: Can Omeprazole be used to prevent stress ulcers?
A: Yes, omeprazole is commonly used for stress ulcer prophylaxis, typically at a dose of 40 mg intravenously once daily.
Q10: What is the role of Omeprazole in treating H. pylori infection?
A: Omeprazole is used in combination with antibiotics (such as Amoxicillin and Clarithromycin) as part of a triple therapy regimen to eradicate H. pylori.
