Drug Monograph
Prilosec (Omeprazole)
omeprazole
Pharmacokinetic Profile
Half-Life
0.5–1 h (but effect lasts ≥24 h)
Metabolism
CYP2C19 (primary), CYP3A4
Protein Binding
~95%
Bioavailability
30–40% (single dose); ~60% (repeated dosing)
Volume of Distribution
0.3–0.4 L/kg
Clinical Information
Drug Class
Proton Pump Inhibitor (substituted benzimidazole)
Available Doses
10, 20, 40 mg capsules; 2.5, 10 mg oral suspension packets; 20 mg OTC tablet
Route
Oral (once or twice daily)
Renal Adjustment
None required
Hepatic Adjustment
Consider dose reduction in hepatic impairment; bioavailability increased ~100%
Pregnancy
Not contraindicated; epidemiologic data have not shown increased risk of major malformations
Lactation
Present in breast milk; use with caution
Schedule
Rx and OTC (20 mg)
Generic Available
Yes (widely)
Pharmacogenomic Note
CYP2C19: Asians have ~4-fold higher exposure (higher PM prevalence); consider dose reduction for EE maintenance
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Active duodenal ulcer | Adults | Monotherapy | FDA Approved |
| H. pylori eradication (to reduce duodenal ulcer recurrence) | Adults | Combination (with clarithromycin ± amoxicillin) | FDA Approved |
| Active benign gastric ulcer | Adults | Monotherapy | FDA Approved |
| Symptomatic GERD | ≥1 year | Monotherapy | FDA Approved |
| Erosive esophagitis (EE) — treatment and maintenance of healing | ≥1 month (treatment); ≥1 year (maintenance) | Monotherapy | FDA Approved |
| Pathological hypersecretory conditions (Zollinger-Ellison syndrome) | Adults | Monotherapy | FDA Approved |
Omeprazole was the first proton pump inhibitor approved (1989) and remains one of the most widely prescribed medications globally. It is available both by prescription and over-the-counter (20 mg for frequent heartburn). Clinical trials have demonstrated that omeprazole 20 mg heals duodenal ulcers within 4 weeks in most patients and is significantly more effective than H2-receptor antagonists for erosive esophagitis. The drug is also integral to H. pylori eradication regimens, where combination therapy has been shown to markedly reduce duodenal ulcer recurrence.
Off-Label Uses
Stress ulcer prophylaxis (ICU): Commonly used in critically ill patients at risk of upper GI bleeding, though guidelines increasingly favor H2-receptor antagonists or enteral nutrition alone in lower-risk patients. Evidence quality: Moderate.
NSAID gastroprotection: Co-prescribed with chronic NSAID use in patients with GI risk factors. ACG guidelines support PPI co-therapy. Evidence quality: High.
Functional dyspepsia: Empiric PPI trial is recommended as initial management by the ACG. Evidence quality: Moderate.
Dosing
Adult Dosing — By Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Active duodenal ulcer | 20 mg once daily | 20 mg once daily | 20 mg/day | 4 weeks; may extend to 8 weeks if incomplete healing Take before eating; swallow capsule whole |
| H. pylori eradication — triple therapy | 20 mg BID + amoxicillin 1000 mg BID + clarithromycin 500 mg BID | — | 20 mg BID | 10 days; if ulcer present at diagnosis, continue omeprazole 20 mg QD for additional 18 days Current ACG guidelines may recommend quadruple therapy based on local resistance patterns |
| H. pylori eradication — dual therapy | 40 mg once daily + clarithromycin 500 mg TID | — | 40 mg/day | 14 days; higher clarithromycin resistance rates with dual therapy Triple therapy preferred when local resistance allows |
| Active benign gastric ulcer | 40 mg once daily | 40 mg once daily | 40 mg/day | 4–8 weeks |
| Symptomatic GERD (no erosions) | 20 mg once daily | 20 mg once daily | 20 mg/day | 4 to 8 weeks; reassess need for continued therapy after this course OTC: 20 mg QD for 14 days; may repeat every 4 months |
| Erosive esophagitis — healing | 20 mg once daily | 20 mg once daily | 20 mg/day | 4–8 weeks; 40 mg dose not superior to 20 mg in controlled trials If not healed after 8 weeks, an additional 4 weeks may be given |
| Erosive esophagitis — maintenance of healing | 20 mg once daily | 20 mg once daily | 20 mg/day | Controlled studies did not extend beyond 12 months Consider 10 mg QD in Asian patients or hepatic impairment |
| Zollinger-Ellison syndrome / pathological hypersecretion | 60 mg once daily | Individualized | 360 mg/day (as 120 mg TID) | Doses >80 mg/day should be divided; titrate to achieve basal acid output <10 mEq/h Some patients have been treated continuously for >5 years |
Pediatric Dosing — By Weight and Indication
| Indication / Age | Body Weight | Dose | Notes |
|---|---|---|---|
| GERD (≥1 year) | 5–<10 kg | 5 mg QD | Up to 4 weeks |
| GERD (≥1 year) | 10–<20 kg | 10 mg QD | Up to 4 weeks |
| GERD (≥1 year) | ≥20 kg | 20 mg QD | Up to 4 weeks |
| EE healing (≥1 month) | Same weight bands | Same doses as GERD | 4–8 weeks; not studied beyond 12 months |
Clinical Pearl: Timing and Administration
Omeprazole should be taken 30–60 minutes before breakfast (or before the first meal of the day) for optimal acid suppression. The delayed-release capsule should be swallowed whole. For patients who cannot swallow capsules, the contents can be sprinkled on applesauce and swallowed immediately without chewing, or the oral suspension packets can be dispersed in water. Efficacy depends on covalent binding to actively secreting proton pumps, which are maximally active after a meal — hence the importance of pre-meal dosing.
Pharmacology
Mechanism of Action
Omeprazole is a prodrug that belongs to the substituted benzimidazole class of proton pump inhibitors. After absorption, it accumulates in the acidic secretory canaliculi of gastric parietal cells, where the low pH environment catalyzes its conversion to the active sulfenamide form. This active metabolite then forms a covalent disulfide bond with cysteine residues on the H+/K+-ATPase (proton pump), irreversibly inhibiting the final step of gastric acid secretion. Because inhibition is irreversible, acid suppression persists long after the drug has been cleared from plasma (typically 24–48 hours), until new proton pump molecules are synthesized. A single 20 mg dose inhibits approximately 70% of proton pumps; maximal acid suppression requires 3–5 days of daily dosing as successive cohorts of newly synthesized pumps are inactivated.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Enteric-coated granules release drug after leaving stomach; bioavailability 30–40% (single dose) rising to ~60% with repeated dosing; Tmax 0.5–3.5 h; food may delay absorption | Increasing bioavailability with repeated dosing reflects reduced first-pass metabolism as acid suppression decreases gastric degradation of the acid-labile drug; take before eating for optimal effect |
| Distribution | Vd 0.3–0.4 L/kg; ~95% protein bound (albumin); concentrates in parietal cell secretory canaliculi via ion trapping | Low systemic Vd but target-site (parietal cell) concentration far exceeds plasma levels due to acid-mediated trapping; protein binding limits dialysis utility |
| Metabolism | Extensively hepatic via CYP2C19 (primary, forming 5-hydroxyomeprazole) and CYP3A4 (forming omeprazole sulfone); CYP2C19 polymorphism creates major inter-individual variability (PM: 5–10-fold higher AUC vs EM); omeprazole inhibits CYP2C19 | CYP2C19 PM phenotype: ~3% Caucasians, 15–20% Asians — have ~4-fold higher exposure; consider dose reduction for EE maintenance in Asians; CYP2C19 inhibition underlies clopidogrel interaction |
| Elimination | t1/2 0.5–1 h (healthy), ~3 h (hepatic impairment); ~77% excreted in urine as metabolites, remainder fecal; <1% unchanged in urine | Despite very short plasma half-life, irreversible covalent pump inhibition provides ≥24 h acid suppression, supporting once-daily dosing; hepatic impairment increases bioavailability ~100% |
Side Effects
1–10%Common (from clinical trials, N=3,096)
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Headache | 7% | Most commonly reported; generally self-limiting |
| Abdominal pain | 5% | Evaluate for underlying pathology if persistent |
| Nausea | 4% | Usually transient; not dose-dependent |
| Diarrhea | 4% | If persistent or severe, consider C. difficile testing |
| Vomiting | 3% | More common in pediatric populations |
| Flatulence | 3% | Related to altered gut flora from acid suppression |
| Upper respiratory infection | 2% | Mechanism unclear; may relate to altered upper GI flora |
| Dizziness | 2% | Usually self-limiting |
| Rash | 2% | Discontinue if severe; evaluate for SLE if systemic features develop |
| Constipation | 2% | Manage with fiber and hydration |
SeriousSerious (Regardless of Frequency)
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| C. difficile-associated diarrhea (CDAD) | Uncommon; risk increases with duration | Any time during or after therapy | Test stool for C. difficile toxin; discontinue PPI if confirmed; initiate directed antibiotic therapy |
| Hypomagnesemia | Rare; reported with ≥3 months use (mostly >1 year) | Months to years | Check serum magnesium if symptoms (tetany, arrhythmia, seizures); supplement and consider PPI discontinuation |
| Bone fractures (hip, wrist, spine) | Observational data; risk with long-term high-dose use | Long-term (≥1 year) | Use lowest effective dose for shortest duration; ensure adequate calcium and vitamin D; FDA warning applies to all PPIs |
| Acute interstitial nephritis | Rare (postmarketing) | Weeks to months | Monitor renal function if symptoms develop; discontinue PPI |
| Cutaneous or systemic lupus erythematosus | Rare (postmarketing) | Days to years after initiation | Discontinue PPI; most SLE cases resolve within weeks of stopping; evaluate for systemic involvement |
| Vitamin B12 deficiency | Rare; with >3 years use | Years | Screen B12 levels in patients on long-term therapy; supplement if deficient |
| Fundic gland polyps | Risk increases with >1 year use | Months to years | Generally benign; use shortest duration of PPI therapy necessary |
| Hypersensitivity (anaphylaxis, angioedema, bronchospasm, urticaria) | Rare (postmarketing) | Any time | Discontinue permanently; contraindicated in patients with known benzimidazole hypersensitivity |
DiscontinuationDiscontinuation and Long-Term Considerations
Short-Term Use (≤8 weeks)
Well tolerated
Discontinuation rates in clinical trials were low and comparable to placebo; generally no rebound symptoms with short courses
Long-Term Discontinuation
Rebound acid hypersecretion
After ≥8 weeks of daily use, abrupt discontinuation may cause rebound acid hypersecretion with worsened heartburn for 1–2 weeks; taper or step-down to H2RA recommended
Long-Term PPI Use: Balancing Risks and Benefits
Current deprescribing guidelines recommend reassessing PPI necessity after 4–8 weeks of treatment for uncomplicated GERD and heartburn. Consider stepping down to the lowest effective dose or transitioning to on-demand use. Long-term continuous therapy is appropriate for patients with Barrett esophagus, severe erosive esophagitis (LA Grade C/D), documented bleeding ulcer history, or Zollinger-Ellison syndrome. For all other patients, periodic reassessment is advised to minimize exposure to potential long-term risks including hypomagnesemia, B12 deficiency, fractures, fundic gland polyps, and C. difficile infection.
Drug Interactions
Omeprazole has a clinically significant drug interaction profile driven by two mechanisms: (1) inhibition of CYP2C19, which can increase exposure to CYP2C19 substrates and, critically, reduce activation of the prodrug clopidogrel; and (2) elevation of gastric pH, which impairs absorption of drugs requiring an acidic environment. Omeprazole is also metabolized by CYP2C19 and CYP3A4, making it susceptible to inducers and inhibitors of these enzymes.
MajorClopidogrel
MechanismOmeprazole inhibits CYP2C19, which is required to convert the prodrug clopidogrel to its active antiplatelet metabolite
EffectReduced antiplatelet activity of clopidogrel; diminished clinical efficacy even when drugs are given 12 hours apart
ManagementAVOID concomitant use; consider pantoprazole (weaker CYP2C19 inhibition) or H2RA if acid suppression is needed
FDA PIMajorRilpivirine
MechanismElevated gastric pH markedly reduces rilpivirine absorption
EffectLoss of virologic suppression and risk of HIV resistance
ManagementCONTRAINDICATED — do not co-administer
FDA PIMajorMethotrexate (high-dose)
MechanismPPIs may inhibit renal tubular secretion of methotrexate, delaying elimination
EffectElevated methotrexate and metabolite levels; increased toxicity risk
ManagementConsider temporary PPI discontinuation in patients receiving high-dose methotrexate; monitor methotrexate levels
FDA PIModerateTacrolimus
MechanismCYP2C19 and/or CYP3A4 inhibition by omeprazole may increase tacrolimus levels
EffectPotential for tacrolimus toxicity (nephrotoxicity, neurotoxicity)
ManagementMonitor tacrolimus trough levels when initiating, adjusting, or discontinuing omeprazole
FDA PIModerateSt. John’s Wort / Rifampin
MechanismStrong induction of CYP2C19 and CYP3A4 substantially reduces omeprazole exposure
EffectReduced acid suppression; potential treatment failure
ManagementAVOID concomitant use
FDA PIModerateVoriconazole
MechanismCombined CYP2C19 and CYP3A4 inhibition more than doubles omeprazole exposure
EffectIncreased omeprazole levels; generally well tolerated but may increase side effects
ManagementDose adjustment of omeprazole not normally required; in ZE syndrome patients on high doses, consider reduction
FDA PIModeratePhenytoin / Diazepam / Cilostazol
MechanismOmeprazole inhibits CYP2C19, delaying clearance of these CYP2C19 substrates
EffectIncreased levels of phenytoin (toxicity risk), diazepam (prolonged sedation), cilostazol (increased exposure)
ManagementMonitor phenytoin levels; reduce cilostazol dose; use caution with diazepam
FDA PIMinorIron / Ketoconazole / Atazanavir (pH-dependent absorption)
MechanismElevated gastric pH reduces dissolution and absorption of drugs requiring acid for solubility
EffectDecreased bioavailability of iron salts, ketoconazole, itraconazole, atazanavir, and other pH-dependent drugs
ManagementMonitor efficacy; separate dosing or use alternative agents; atazanavir should not be co-administered without ritonavir boosting
FDA PIMonitoring
- Symptom Response4–8 weeks after initiation
RoutineReassess need for continued PPI therapy. If no erosive disease or high-risk features, consider step-down to lowest effective dose, on-demand dosing, or H2RA switch. Do not continue indefinitely without clinical indication. - Serum MagnesiumBaseline and periodically in long-term use
Trigger-basedHypomagnesemia reported with prolonged PPI use (≥3 months, most cases >1 year). Check if symptoms suggest low magnesium (tetany, tremor, arrhythmias, seizures). Also consider monitoring calcium in patients with pre-existing hypocalcemia risk. - Vitamin B12Periodically in >3 years use
Trigger-basedChronic acid suppression may impair cyanocobalamin absorption. Screen if symptomatic (fatigue, neuropathy, macrocytosis). - Bone DensityPer osteoporosis screening guidelines
Trigger-basedFDA class-wide warning for fracture risk with long-term, high-dose PPI use. Ensure adequate calcium and vitamin D. Causal relationship uncertain from newer data but prudence remains warranted. - Chromogranin A (CgA)Before testing for neuroendocrine tumors
Trigger-basedPPIs elevate CgA, causing false-positive results. Stop omeprazole at least 14 days before CgA measurement. Use the same laboratory for serial tests. - Renal FunctionIf new symptoms on long-term use
Trigger-basedAcute interstitial nephritis reported as a rare PPI class effect. Check creatinine if new renal symptoms (fever, rash, eosinophilia, rising creatinine).
Contraindications & Cautions
Absolute Contraindications
- Hypersensitivity to substituted benzimidazoles (omeprazole, esomeprazole, lansoprazole, etc.) or any excipient: Reactions include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, and urticaria.
- Co-administration with rilpivirine-containing products: Elevated gastric pH drastically reduces rilpivirine absorption, risking HIV treatment failure and resistance.
Relative Contraindications (Specialist Input Recommended)
- Concurrent clopidogrel therapy: FDA warning advises avoiding concomitant use due to reduced clopidogrel activation. If acid suppression is essential, consider pantoprazole or an H2RA.
- Hepatic impairment: Bioavailability increases approximately 100% compared with IV dosing. Consider dose reduction (maximum 20 mg daily for EE maintenance). Asian patients with CYP2C19 PM phenotype may also require dose reduction.
Use with Caution
- Long-term use (>8 weeks) without clear indication: Reassess regularly. Beers criteria flag PPI use >8 weeks in elderly without high-risk indication. Risk of C. difficile, hypomagnesemia, B12 deficiency, fractures, and fundic gland polyps.
- Patients at risk of osteoporosis: Use lowest effective dose; ensure calcium/vitamin D supplementation.
- Patients with suspected gastric malignancy: Symptomatic improvement with PPI therapy does not exclude malignancy. Endoscopic evaluation should be completed before initiating long-term therapy.
FDA Class-Wide Regulatory Warning
PPI-Associated Fracture Risk
The FDA issued a class-wide safety communication (2010, updated 2011) regarding the possible increased risk of hip, wrist, and spine fractures associated with long-term (≥1 year), high-dose PPI use. The greatest risk was observed in patients who received high doses or used PPIs for one year or more, though fractures were also reported with shorter durations. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to their clinical condition.
Patient Counselling
Purpose of Therapy
Omeprazole reduces the amount of acid your stomach produces, helping to heal ulcers, relieve heartburn, and protect your esophagus from acid damage. It works best when taken consistently as prescribed.
How to Take
Take omeprazole 30 to 60 minutes before breakfast (or your first meal). Swallow the capsule whole with water; do not crush, chew, or open it unless your doctor instructs you to sprinkle it on applesauce. If you miss a dose, take it as soon as you remember but do not double the dose. For over-the-counter use, do not take for more than 14 days without consulting a healthcare provider.
Duration of Use
Tell patientOmeprazole is generally intended for short-term use (4–8 weeks for most conditions). Your doctor will let you know if longer use is needed. Do not continue taking it indefinitely without medical supervision, especially if purchased over the counter.
Call prescriberIf symptoms persist after completing the recommended course, or if symptoms return after stopping the medication.
Alarm Symptoms
Tell patientHeartburn can sometimes mask more serious conditions. Pay attention to warning signs that require urgent evaluation.
Call prescriberImmediately if you experience difficulty or pain when swallowing, vomiting blood or material that looks like coffee grounds, bloody or black stools, unexplained weight loss, or chest pain.
Diarrhea
Tell patientThis medication may increase the risk of a bacterial infection in the bowel called C. difficile, which can cause watery diarrhea that does not go away.
Call prescriberIf you develop persistent watery diarrhea, abdominal pain, or fever, especially if taking or recently finished antibiotics.
Bone Health (Long-Term Use)
Tell patientLong-term use of acid-reducing medications has been associated with a possible increased risk of bone fractures. Ensure you get adequate calcium and vitamin D through diet or supplements.
Call prescriberIf you have risk factors for osteoporosis or experience a fracture while on long-term PPI therapy.
Drug Interactions
Tell patientOmeprazole can interact with blood thinners (especially clopidogrel), seizure medications, certain HIV drugs, and antifungal medications. Always inform your healthcare providers about all medications you take, including over-the-counter products.
Call prescriberBefore starting any new medication, especially if you are also taking a blood thinner.
Sources
Regulatory (PI / SmPC)
- PRILOSEC (omeprazole magnesium) for delayed-release oral suspension. Full Prescribing Information. AstraZeneca / Covis Pharma. Revised 2023. FDA Label (2023)Primary reference for indications, dosing, adverse reactions, drug interactions, and pharmacokinetics of the branded formulation.
- Omeprazole delayed-release capsules. Full Prescribing Information. NorthStar Rx / generic manufacturers. Drugs.com PIGeneric label with comprehensive interaction tables and pediatric dosing data.
Key Clinical Trials
- Bardhan KD, Bianchi Porro G, Bose K, et al. A comparison of two different doses of omeprazole versus ranitidine in treatment of duodenal ulcers. J Clin Gastroenterol. 1986;8(4):408-413. doi:10.1097/00004836-198608000-00008Early landmark trial establishing superiority of omeprazole over ranitidine for duodenal ulcer healing.
- Lind T, Veldhuyzen van Zanten S, Unge P, et al. Eradication of Helicobacter pylori using one-week triple therapies combining omeprazole with two antimicrobials: the MACH I Study. Helicobacter. 1996;1(3):138-144. doi:10.1111/j.1523-5378.1996.tb00027.xKey trial establishing omeprazole-based triple therapy for H. pylori eradication with >90% success rates.
- Richter JE, Kahrilas PJ, Johanson J, et al. Efficacy and safety of esomeprazole compared with omeprazole in GERD patients with erosive esophagitis: a randomized controlled trial. Am J Gastroenterol. 2001;96(3):656-665. doi:10.1111/j.1572-0241.2001.03600.xComparative trial of omeprazole 20 mg vs esomeprazole in erosive esophagitis; established benchmark healing rates.
Guidelines
- Katz PO, Dunbar KB, Schnoll-Sussman FH, et al. ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol. 2022;117(1):27-56. doi:10.14309/ajg.0000000000001538Current ACG guideline with PPI dosing recommendations, step-down strategies, and indications for long-term therapy.
- Chey WD, Leontiadis GI, Howden CW, et al. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017;112(2):212-239. doi:10.1038/ajg.2016.563ACG H. pylori guideline recommending PPI-based triple or quadruple therapy with resistance-guided antibiotic selection.
- Farrell B, Pottie K, Thompson W, et al. Deprescribing proton pump inhibitors: evidence-based clinical practice guideline. Can Fam Physician. 2017;63(5):354-364. PMID:28500192Deprescribing guideline recommending PPI reduction or cessation in patients without high-risk indications after 4–8 weeks.
Mechanistic / Basic Science
- Sachs G, Shin JM, Howden CW. Review article: the clinical pharmacology of proton pump inhibitors. Aliment Pharmacol Ther. 2006;23(Suppl 2):2-8. doi:10.1111/j.1365-2036.2006.02943.xAuthoritative review of the mechanism of irreversible H+/K+-ATPase inhibition and parietal cell pharmacology.
Pharmacokinetics / Special Populations
- Shah N, Gossman W. Omeprazole. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Updated February 2023. NBK539786Comprehensive clinical pharmacology review covering CYP2C19 polymorphism, dosing, interactions, and monitoring.
- Dean L, Kane M. Omeprazole Therapy and CYP2C19 Genotype. In: Pratt VM, et al., editors. Medical Genetics Summaries. Bethesda (MD): NCBI; 2021. NBK100895CPIC/DPWG pharmacogenomic review detailing CYP2C19 allele-specific dosing recommendations for PPIs.
- FDA Drug Safety Communication: Possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors. FDA. Revised March 2011. FDA.govFDA class-wide safety communication on PPI-associated fracture risk with long-term, high-dose use.
- FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of proton pump inhibitor drugs. FDA. Revised March 2011. FDA.govFDA safety communication on PPI-associated hypomagnesemia requiring monitoring in prolonged use.