PRILOSEC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PRILOSEC (PRILOSEC).
Omeprazole is a proton pump inhibitor that irreversibly inhibits the H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells, thereby blocking the final step of gastric acid secretion.
| Metabolism | Omeprazole is extensively metabolized in the liver primarily by CYP2C19 (major) and CYP3A4 (minor) isoenzymes, producing inactive metabolites including omeprazole sulfone and hydroxyomeprazole. |
| Excretion | Renal: ~77% as metabolites; fecal: ~20% as metabolites (biliary/fecal). Unchanged drug negligible. |
| Half-life | Terminal elimination half-life: 0.5–1 hour in healthy subjects (elimination phase); clinical context: acid suppression persists >24 hours due to irreversible binding to parietal cell H+/K+-ATPase. |
| Protein binding | ~95% bound to albumin and alpha1-acid glycoprotein. |
| Volume of Distribution | 0.3–0.5 L/kg, indicating distribution into total body water and extracellular fluid. |
| Bioavailability | Oral (delayed-release capsule): 30–40% after a single dose (increases to 50–60% with repeated dosing due to reduced acid degradation). IV: 100%. |
| Onset of Action | Oral: peak effect on acid secretion within 2–4 hours after a single dose; repeated dosing achieves maximal effect by 4 days. IV: onset within minutes but peak effect still requires 2–4 hours. |
| Duration of Action | Duration of acid suppression >24 hours after a single dose; with repeated daily dosing, effect persists up to 72 hours after last dose, but full recovery of acid secretion takes 3–5 days. |
20 mg orally once daily before a meal for 4-8 weeks for GERD; for duodenal ulcer, 20 mg once daily for 4 weeks; for Zollinger-Ellison syndrome, initial dose 60 mg orally once daily, titrate up to 120 mg three times daily as needed.
| Dosage form | CAPSULE, DELAYED REL PELLETS |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. For severe renal impairment (CrCl < 10 mL/min), maximum dose 20 mg daily due to limited data. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: maximum dose 20 mg daily. Child-Pugh C: avoid use or reduce dose; specific guidelines not established, use with caution. |
| Pediatric use | For GERD: 1-16 years: weight-based dosing: 5-10 kg: 5 mg once daily; 10-20 kg: 10 mg once daily; >20 kg: 20 mg once daily. For erosive esophagitis: 1-16 years: weight-based 5-10 kg: 5 mg once daily; 10-20 kg: 10 mg once daily; >20 kg: 20 mg once daily. For adolescents: same as adult dosing. |
| Geriatric use | No specific dose adjustment required, but consider increased risk of osteoporosis-related fractures, Clostridium difficile infection, and vitamin B12 deficiency with long-term use. Use lowest effective dose for shortest duration. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PRILOSEC (PRILOSEC).
| Breastfeeding | Omeprazole is secreted in human breast milk in low amounts; estimated infant dose is approximately 0.4% of maternal weight-adjusted dose. M/P ratio is not established. Clinical studies report no adverse effects in breastfed infants. The benefit of breastfeeding should be weighed against the potential risk of infant exposure. |
| Teratogenic Risk | First trimester: Limited human data suggest no increased risk of major malformations. Second and third trimesters: No evidence of fetal toxicity based on observational studies. Omeprazole is classified as FDA Pregnancy Category C prior to 2014; current evidence does not indicate a significant teratogenic risk across all trimesters. |
■ FDA Black Box Warning
None
| Serious Effects |
Known hypersensitivity to omeprazole, substituted benzimidazoles, or any component of the formulation; coadministration with rilpivirine-containing products or with methotrexate (high-dose).
| Precautions | Potential increased risk of Clostridium difficile-associated diarrhea; hypomagnesemia (with prolonged use); vitamin B12 deficiency (with long-term therapy); acute interstitial nephritis; bone fracture risk (related to high-dose or long-term use); gastric malignancies (likely due to underlying conditions, not drug); interaction with clopidogrel (reduced efficacy via CYP2C19 inhibition); interference with laboratory tests (e.g., chromogranin A); and severe cutaneous adverse reactions (e.g., Stevens-Johnson syndrome). |
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| Fetal Monitoring | Routine prenatal care; no specific fetal monitoring required. Monitor maternal symptoms of GERD or peptic ulcer disease. In long-term therapy, monitor vitamin B12 and magnesium levels; consider bone density assessment if prolonged use. |
| Fertility Effects | Animal studies at high doses showed reduced fertility parameters; human data are insufficient to conclude a significant effect on fertility. Omeprazole may cause gynecomastia in males, but impact on spermatogenesis is not clearly documented. |