Omeprazole

Generic Name: Omeprazole
Brand Names: Prilosec (US), Losec (UK/EU), Zegerid (US – with sodium bicarbonate), Omez, Omep, Omizole
Drug Class: Proton Pump Inhibitor (PPI)
Formulations:
– Delayed-release capsules: 10 mg, 20 mg, 40 mg
– Delayed-release tablets: 10 mg, 20 mg
– Oral suspension powder
– Oral disintegrating tablets (in some regions)
Route of Administration: Oral (by mouth), occasionally nasogastric (off-label)

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Therapeutic Indications and Clinical Applications

Omeprazole is indicated for short-term and long-term treatment of acid-related disorders. It inhibits gastric acid secretion and supports mucosal healing in a wide array of gastrointestinal conditions.

Approved and Common Uses:

1. Gastroesophageal Reflux Disease (GERD)
   – Symptomatic relief of heartburn
   – Healing of erosive esophagitis
   – Maintenance of healing

2. Peptic Ulcer Disease (PUD)
   – Duodenal and gastric ulcer treatment
   – Prevention of ulcer recurrence
   – NSAID-induced ulcer prophylaxis

3. Helicobacter pylori eradication therapy
   – As part of triple or quadruple combination regimens

4. Zollinger-Ellison Syndrome and other pathological hypersecretory conditions
   – Long-term acid suppression

5. Dyspepsia (functional and non-ulcer)
   – Off-label in some regions
   – Used for acid-related upper abdominal discomfort

6. Stress ulcer prophylaxis in hospitalized patients
   – In specific high-risk intensive care patients

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Mechanism of Action

Omeprazole is a prodrug that becomes activated in the acidic environment of gastric parietal cells, where it binds irreversibly to H⁺/K⁺-ATPase enzymes (proton pumps). This halts the final step of gastric acid production.

Physiological Results:

• Profound inhibition of both basal and stimulated gastric acid secretion

• Suppresses meal-related and nocturnal acid secretion

• Allows gastric and duodenal mucosa to heal by reducing acidity

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Pharmacokinetics

• Absorption: Rapid from small intestine; peak plasma levels in 1–2 hours

• Bioavailability: ~30–40% after single dose, increases with repeated use

• Metabolism: Hepatic (primarily by CYP2C19 and CYP3A4)

• Protein Binding: >95%

• Half-life: 0.5–1 hour (short plasma half-life, long duration due to irreversible binding)

• Excretion: Metabolites eliminated in urine (80%) and feces (20%)

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Dosing and Administration

1. GERD (erosive and non-erosive):

• 20 mg once daily for 4–8 weeks

• Maintenance: 10–20 mg once daily

2. Duodenal Ulcer:

• 20 mg once daily for 4 weeks (extend to 8 weeks if necessary)

3. Gastric Ulcer:

• 20–40 mg once daily for 4–8 weeks

4. H. pylori Eradication (Triple Therapy):

• 20 mg BID + Amoxicillin 1000 mg BID + Clarithromycin 500 mg BID for 10–14 days

5. Zollinger-Ellison Syndrome:

• Starting dose: 60 mg/day; titrate up to 120 mg/day in divided doses as needed

6. NSAID Ulcer Prophylaxis:

• 20 mg once daily

Pediatric Dosing (where approved):

• GERD: weight-based dosing

• Infants: oral suspension or granules mixed with liquid

Administration Tips:

• Take on empty stomach, ideally 30–60 minutes before breakfast

• Swallow capsules whole; do not crush or chew

• Suspension formulation can be used for NG/PEG administration

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Contraindications

• Known hypersensitivity to omeprazole, substituted benzimidazoles, or formulation excipients

• Concomitant use with rilpivirine (due to decreased antiviral efficacy)

• Use with caution in patients with suspected gastrointestinal malignancy (due to symptom masking)

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Warnings and Precautions

1. Clostridioides difficile–associated diarrhea (CDAD):
   – Higher risk with long-term use

2. Hypomagnesemia (with prolonged use):
   – Monitor if used >3 months; may present with tetany, arrhythmias, or seizures

3. Vitamin B12 Deficiency (with long-term therapy):
   – Gastric acid is essential for B12 absorption; check levels periodically

4. Fracture Risk (hip, wrist, spine):
   – Increased with high doses or long-term use (>1 year)

5. Lupus erythematosus (cutaneous or systemic):
   – Rare immune-mediated events reported with PPIs

6. Rebound acid hypersecretion upon discontinuation
   – May occur; consider gradual tapering after prolonged use

7. Interstitial nephritis:
   – Acute interstitial nephritis has been reported; monitor renal function

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Adverse Effects

Common (≥1%):

• Headache

• Diarrhea

• Nausea

• Flatulence

• Abdominal pain

• Constipation

• Dizziness

Less Common / Serious (rare):

• Hypomagnesemia

• Rash or pruritus

• Hepatic enzyme elevation

• Acute interstitial nephritis

• Osteoporosis-related fractures

• Pancytopenia (rare)

• Vitamin B12 deficiency (long-term)

• Visual disturbances

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Drug Interactions

1. Clopidogrel (Plavix):
   – Omeprazole inhibits CYP2C19, reducing clopidogrel activation
   – Avoid co-administration or consider alternative PPI (pantoprazole, rabeprazole)

2. Drugs requiring acidic pH for absorption:
   – ↓ Absorption of: atazanavir, rilpivirine, ketoconazole, itraconazole, erlotinib
   – Avoid or separate dosing

3. Warfarin:
   – May increase INR; monitor closely

4. Methotrexate (high-dose):
   – PPIs may delay elimination, increasing toxicity risk
   – Consider withholding PPI during high-dose methotrexate

5. Phenytoin, diazepam, digoxin, tacrolimus:
   – May increase serum levels; monitor concentrations where appropriate

6. Cilostazol:
   – ↑ Exposure; may require dose adjustment

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Monitoring Parameters

• Symptom relief (heartburn, ulcer pain, etc.)

• Serum magnesium, especially during long-term use or in combination with diuretics

• Vitamin B12 (if long-term therapy >1 year)

• Renal function if suspected interstitial nephritis

• Bone density in patients with osteoporosis or fracture risk

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Use in Special Populations

Pregnancy:
– Category C (US); studies in animals show no harm; human data limited
– Often used in pregnancy when clinically indicated

Lactation:
– Omeprazole is excreted in breast milk; use with caution

Pediatrics:
– Approved for use in GERD and ulcer treatment in children >1 year (depending on region)

Geriatrics:
– Generally safe; adjust dose if hepatic impairment present

Renal Impairment:
– No dosage adjustment needed

Hepatic Impairment:
– Consider dose adjustment; monitor closely in moderate to severe impairment

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Patient Counseling Information

• Take 30–60 minutes before meals, usually breakfast

• Do not crush or chew capsules or tablets

• If using suspension, shake well and administer promptly

• Report persistent diarrhea, muscle cramps, seizures, or fatigue

• Avoid alcohol and tobacco (they may worsen reflux)

• Use lowest effective dose for shortest possible duration

• Do not stop suddenly after long-term use to avoid rebound acid symptoms

• Inform all healthcare providers if taking omeprazole due to interaction potential

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Comparative Profile vs. Other PPIs

PPI	Metabolism	Onset	Duration	Clopidogrel Interaction	Acid Stability
Omeprazole	CYP2C19, CYP3A4	1–2 hours	>24 hrs	High (avoid)	Moderate
Esomeprazole	CYP2C19, CYP3A4	1–2 hours	>24 hrs	Moderate	High
Rabeprazole	Non-enzymatic + CYPs	~1 hour	>24 hrs	Minimal	High
Pantoprazole	CYP2C19	2.5 hours	>24 hrs	Minimal	High
Lansoprazole	CYP2C19	1.5 hours	>24 hrs	Moderate	Moderate

Storage and Stability

• Store at room temperature (15–25°C)

• Protect from moisture and heat

• Do not freeze liquid formulations

• Keep out of reach of children

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Availability and Regulatory Status

• Widely available worldwide in branded and generic forms

• OTC and prescription versions depending on indication and strength

• Included in WHO Model List of Essential Medicines

• Covered in international guidelines for GERD and PUD