omeprazole
Brand: Prilosec
Prototype Drug
Drug Class: proton pump inhibitor
Drug Family: GI agent
Subclass: irreversible H+/K+-ATPase inhibitor (sulfonamide prodrug)
Organ Systems: gastrointestinal
Mechanism of Action
Prodrug activated in acidic environment of secretory canaliculus; active sulfenamide irreversibly binds H+/K+-ATPase; suppresses 95%+ of gastric acid production.
H+/K+-ATPase (proton pump) in parietal cells
Indications
- GERD
- peptic ulcer disease (duodenal and gastric)
- H. pylori eradication (component of triple therapy)
- Zollinger-Ellison syndrome
- NSAID-induced ulcer prophylaxis
- stress ulcer prophylaxis (ICU)
Contraindications
- concurrent rilpivirine or atazanavir (pH-dependent absorption)
- hypersensitivity
Adverse Effects
Common
- headache
- diarrhea
- nausea
- abdominal pain
Serious
- Clostridium difficile infection (pH-dependent)
- hypomagnesemia (prolonged use)
- hip/spine fractures (long-term, high dose)
- vitamin B12 deficiency (long-term)
- CKD (epidemiological association)
Pharmacokinetics (ADME)
| Absorption | ~35-40% bioavailability (acid-labile; enteric-coated) |
| Distribution | moderate Vd |
| Metabolism | extensive hepatic CYP2C19 (major), CYP3A4 |
| Excretion | renal 77% |
| Half-life | 0.5-3 hours |
| Onset | 1-3.5 hours |
| Peak | 1-2 hours |
| Duration | 24+ hours (accumulates with repeated dosing) |
| Protein Binding | 95-96% |
| Vd | 0.3-0.4 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| clopidogrel | CYP2C19 inhibition reduces clopidogrel activation — reduce efficacy; use pantoprazole | moderate |
| ketoconazole/itraconazole | reduced absorption due to pH increase | major |
| methotrexate | reduces renal elimination of MTX — toxicity risk | major |
| atazanavir/rilpivirine | pH-dependent absorption reduced — contraindicated | major |
Nursing Considerations
- Take 30-60 minutes before first meal for maximum efficacy (inactive pump activation required)
- Demote-cap: crush and dissolve enteric granules in water for NG tube administration
- Long-term use >8 weeks: reassess need; lowest effective dose
- Monitor Mg2+ with prolonged use (>1 year)
- C. diff risk with prolonged acid suppression
Clinical Pearls
- Irreversible binding: new pump synthesis needed for recovery; full effect takes 2-4 days
- PPIs reduce clopidogrel activation: use pantoprazole (less CYP2C19 inhibition) if PPI required with clopidogrel
Safety Profile
Pregnancy generally-safe
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.