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. |
| Molecular Weight | 345.42 |
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 | Human data suggest low risk; no evidence of teratogenicity in large cohort studies. |
| 2nd trimester | No known harm; may be used if clinically indicated. |
| 3rd trimester | No known harm; may be used if clinically indicated. |
Clinical note
Comprehensive clinical and safety monograph for PRILOSEC (PRILOSEC).
| Placental transfer | Crosses placenta with cord blood levels about 50% of maternal serum levels. |
| Breastfeeding | Excreted into breast milk in low amounts; not expected to cause adverse effects in infants. Use with caution, especially in preterm neonates. |
| Lactation Rating | L2 (Possibly Compatible) or Safe |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to omeprazole or substituted benzimidazolesConcomitant use with rilpivirine-containing products
| 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). |
| Food/Dietary | Take on an empty stomach at least 30 minutes before meals to ensure maximal absorption. Avoid high-fat meals that may delay absorption. No specific food restrictions, but acidic foods may exacerbate symptoms. May reduce absorption of vitamin B12 with long-term use. |
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| 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. |
| 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. |
| Clinical Pearls | Do not crush or chew delayed-release capsules; administer before meals for optimal acid suppression. Consider acid suppression before endoscopy or pH monitoring. May increase risk of Clostridioides difficile infection and hypomagnesemia with prolonged use. Interaction with clopidogrel reduces efficacy; avoid concomitant use or use alternative PPI. |
| Patient Advice | Take this medication before the first meal of the day, typically 30-60 minutes before eating. · Swallow the capsules whole; do not crush, chew, or open them. · Avoid taking with other medications that reduce stomach acid unless directed by your doctor. · If you miss a dose, take it as soon as possible unless it's almost time for the next dose, then skip the missed dose. · Report any symptoms of Clostridioides difficile infection such as watery or bloody stools, fever, or abdominal cramps. · Long-term use may increase risk of bone fractures, especially in older adults; discuss calcium and vitamin D supplementation with your doctor. |