Introduction
Prilosec (omeprazole) is a proton pump inhibitor (PPI) that reduces gastric acid secretion through irreversible inhibition of the H+/K+ ATPase enzyme system in gastric parietal cells. First approved by the FDA in 1989, it remains widely prescribed for various acid-related gastrointestinal disorders. Available in both prescription and over-the-counter formulations, Prilosec has become one of the most commonly used medications worldwide for managing gastroesophageal reflux disease (GERD) and peptic ulcer disease.
Mechanism of Action
Omeprazole is a substituted benzimidazole that functions as a prodrug. It accumulates in the acidic environment of parietal cells where it undergoes conversion to its active form, a sulfenamide. The active metabolite forms covalent disulfide bonds with cysteine residues on the luminal surface of the H+/K+ ATPase proton pump, resulting in irreversible inhibition. This effectively blocks the final step of gastric acid production, leading to prolonged suppression of basal and stimulated acid secretion regardless of the stimulus. Maximum acid suppression typically occurs within 4 days of repeated daily dosing.
Indications
FDA-approved indications include:
- Healing of erosive esophagitis
- Maintenance healing of erosive esophagitis
- Symptomatic gastroesophageal reflux disease (GERD)
- Active duodenal ulcer
- Active benign gastric ulcer
- Helicobacter pylori eradication (in combination with antibiotics)
- Pathological hypersecretory conditions (Zollinger-Ellison syndrome)
- Risk reduction of upper gastrointestinal bleeding in critically ill patients
Over-the-counter formulation is indicated for:
- Frequent heartburn (occurring 2 or more days per week)
Dosage and Administration
Adults:- GERD: 20 mg once daily for 4-8 weeks
- Erosive esophagitis: 20-40 mg once daily for 4-8 weeks
- Maintenance therapy: 20 mg once daily
- H. pylori eradication: 20 mg twice daily with amoxicillin and clarithromycin for 10-14 days
- Gastric ulcer: 40 mg once daily for 4-8 weeks
- Duodenal ulcer: 20 mg once daily for 4 weeks
- Hypersecretory conditions: Initial 60 mg once daily, adjust based on response (doses up to 120 mg three times daily have been used)
- Hepatic impairment: Maximum dose 20 mg daily for severe impairment
- Renal impairment: No dosage adjustment necessary
- Geriatric patients: No dosage adjustment necessary
- Pediatric patients: Dosing based on weight (consult specific guidelines)
Administration: Should be taken before meals, preferably in the morning. Capsules should be swallowed whole; do not crush or chew. For patients with difficulty swallowing, capsules may be opened and contents sprinkled on applesauce or administered via nasogastric tube.
Pharmacokinetics
Absorption: Rapidly absorbed from the small intestine with bioavailability of approximately 30-40% due to first-pass metabolism. Bioavailability increases with repeated dosing. Food may decrease absorption; optimal administration is on an empty stomach. Distribution: Protein binding is approximately 95%, primarily to albumin. Volume of distribution is approximately 0.3 L/kg. Metabolism: Extensively metabolized in the liver via the cytochrome P450 system, primarily CYP2C19 and CYP3A4. Metabolites include 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, substituted benzimidazoles, or any component of the formulation
- Concomitant use with rilpivirine-containing products
- Use of delayed-release formulations in patients with hereditary problems of fructose intolerance (contains sorbitol)
Warnings and Precautions
Bone Fracture: Long-term (≥1 year) and high-dose therapy may be associated with increased risk of osteoporosis-related fractures of hip, wrist, or spine. Clostridium difficile-Associated Diarrhea: PPI therapy may increase risk of CDAD; consider diagnosis in patients with persistent diarrhea. Acute Interstitial Nephritis: Has been observed with PPIs; may occur at any time during therapy. Discontinue if occurs. Cutaneous and Systemic Lupus Erythematosus: New onset or exacerbation of existing lupus has been reported. Vitamin B12 Deficiency: Long-term therapy may lead to malabsorption of vitamin B12. Hypomagnesemia: Rare but serious cases reported with prolonged PPI use. Monitor magnesium levels prior to and periodically during long-term therapy. Fundic Gland Polyps: Long-term use associated with increased risk of fundic gland polyps.Drug Interactions
CYP2C19 Substrates: May increase concentrations of drugs metabolized by CYP2C19 (e.g., diazepam, warfarin, phenytoin) CYP2C19 Inhibitors: May increase omeprazole concentrations (e.g., fluvoxamine) Drugs Requiring Acidic pH for Absorption: Reduced absorption of drugs such as ketoconazole, iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil Clopidogrel: May reduce antiplatelet effect due to CYP2C19 inhibition Methotrexate: May increase methotrexate levels St. John's Wort: May decrease omeprazole concentrations Tacrolimus: May increase tacrolimus exposureAdverse Effects
Common (≥1%):- Headache (7%)
- Abdominal pain (5%)
- Nausea (4%)
- Diarrhea (4%)
- Constipation (3%)
- Flatulence (3%)
- Vomiting (3%)
- Acute interstitial nephritis
- Clostridium difficile-associated diarrhea
- Bone fracture
- Hypomagnesemia
- Vitamin B12 deficiency
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Erythema multiforme
Monitoring Parameters
- Symptom improvement and resolution
- For long-term therapy: periodic magnesium levels, vitamin B12 status in patients with risk factors
- Bone density assessment in patients on long-term therapy with risk factors for osteoporosis
- Renal function in patients with suspected acute interstitial nephritis
- Signs and symptoms of gastrointestinal infection
- Hepatic function in patients with pre-existing liver disease
Patient Education
- Take medication 30-60 minutes before first meal of the day
- Swallow capsules whole; do not crush, chew, or open unless instructed
- Report any signs of allergic reaction (rash, itching, swelling)
- Notify healthcare provider if diarrhea persists or worsens
- Long-term use may require monitoring of magnesium and vitamin B12 levels
- Discuss calcium and vitamin D supplementation if on long-term therapy
- Do not use OTC formulation for more than 14 days without medical consultation
- Report any new or worsening joint pain or skin lesions
- Inform all healthcare providers of PPI use, especially before starting new medications
References
1. Shin JM, Sachs G. Pharmacology of proton pump inhibitors. Curr Gastroenterol Rep. 2008;10(6):528-534. 2. Omeprazole package insert. AstraZeneca Pharmaceuticals LP. 3. Strand DS, Kim D, Peura DA. 25 years of proton pump inhibitors: a comprehensive review. Gut Liver. 2017;11(1):27-37. 4. FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of Proton Pump Inhibitor drugs. U.S. Food and Drug Administration. 2011. 5. Moayyedi P, Leontiadis GI. The risks of PPI therapy. Nat Rev Gastroenterol Hepatol. 2012;9(3):132-139. 6. Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108(3):308-328. 7. Wedemeyer RS, Blume H. Pharmacokinetic drug interaction profiles of proton pump inhibitors: an update. Drug Saf. 2014;37(4):201-211. 8. Heidelbaugh JJ, Kim AH, Chang R, Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Therap Adv Gastroenterol. 2012;5(4):219-232.