OMEPRAZOLE
Clinical safety rating: safe
Can reduce absorption of drugs requiring gastric pH for absorption (eg ketoconazole) May increase risk of Clostridium difficile-associated diarrhea and bone fractures with long-term use.
Proton pump inhibitor that irreversibly inhibits the H+/K+ ATPase enzyme system at the secretory surface of gastric parietal cells, blocking the final step of gastric acid secretion.
| Metabolism | Extensively metabolized in the liver by CYP2C19 and CYP3A4; minor contribution of CYP2C9 and CYP2D6. Metabolites are inactive; primarily excreted in urine. |
| Excretion | Approximately 77% of a dose is excreted in urine (as metabolites, including hydroxyomeprazole and the corresponding carboxylic acid and sulfone derivatives), and about 18% is eliminated in feces via biliary excretion. Less than 1% of the parent drug is excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is approximately 0.5–1 hour. However, the pharmacodynamic effect (gastric acid suppression) lasts much longer due to irreversible binding to the proton pump. The half-life is prolonged in patients with hepatic impairment (up to 3–4 hours in cirrhosis) and in CYP2C19 poor metabolizers (up to 2–3 hours). |
| Protein binding | Approximately 95% bound to plasma proteins, primarily albumin and alpha1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 0.2–0.5 L/kg (approximately 15–30 L in a 70 kg adult). This low Vd indicates limited extravascular distribution, consistent with high protein binding and confinement to extracellular fluid. |
| Bioavailability | Oral delayed-release: 30–40% (first-pass metabolism reduces bioavailability; increases to 60% with repeated dosing due to decreased clearance). Oral immediate-release: 30–40% (with sodium bicarbonate). Intravenous: 100%. |
| Onset of Action | Oral (immediate-release): Onset of antisecretory effect occurs within 1 hour, with maximal effect after 2–4 hours; single dose reduces acid secretion by 50%. Oral (delayed-release): Onset within 2–3 hours. Intravenous: Onset with 30 minutes for suppression of acid secretion. |
| Duration of Action | Duration of acid suppression is dose-dependent, lasting up to 24 hours after a single oral dose due to accumulation in parietal cells. After discontinuation, gastric acid secretion gradually returns over 3–5 days. Continuous therapy leads to sustained acid suppression throughout the dosing interval. |
| Molecular Weight | 345.42 |
20-40 mg orally once daily before a meal for 4-8 weeks.
| Dosage form | CAPSULE, DELAYED REL PELLETS |
| Renal impairment | No adjustment required for any degree of renal impairment. |
| Liver impairment | In severe hepatic impairment (Child-Pugh Class C), maximum dose is 20 mg daily. |
| Pediatric use | Children 1-16 years: weight <20 kg: 10 mg once daily; weight ≥20 kg: 20 mg once daily. For erosive esophagitis, dose may be increased to 20 mg (if <20 kg) or 40 mg (if ≥20 kg) once daily. |
| Geriatric use | No dose adjustment generally needed; consider reduced starting dose in frail elderly due to potential increased systemic exposure. |
| 1st trimester | No evidence of increased risk of major congenital malformations based on large epidemiological studies. Use only if clearly needed. |
| 2nd trimester | Considered generally safe; no known fetal risk. Use only if clearly needed. |
| 3rd trimester | Considered generally safe; no known fetal risk. Use only if clearly needed. |
Clinical note
Can reduce absorption of drugs requiring gastric pH for absorption (eg ketoconazole) May increase risk of Clostridium difficile-associated diarrhea and bone fractures with long-term use.
| FDA category | Animal |
| Placental transfer | Crosses the placenta; fetal concentrations are approximately 50% of maternal levels. |
| Breastfeeding |
■ FDA Black Box Warning
None.
| Common Effects | erosive esophagitis |
| Serious Effects |
Hypersensitivity to omeprazole or substituted benzimidazolesConcomitant use with rilpivirine-containing productsConcomitant use with nelfinavir
| Precautions | Clostridioides difficile infection risk with prolonged use, Bone fracture risk (hip, wrist, spine) with long-term or high-dose use, Hypomagnesemia with prolonged use (especially with digoxin or diuretics), Vitamin B12 deficiency with long-term use, Interference with absorption of drugs requiring acidic pH (e.g., ketoconazole), Rebound acid hypersecretion upon discontinuation, Acute interstitial nephritis, Cutaneous lupus erythematosus, Subacute cutaneous lupus erythematosus |
| Food/Dietary | Take on an empty stomach; avoid foods that increase acid production (e.g., caffeine, spicy foods, citrus, fatty foods) as they may reduce effectiveness; alcohol can worsen symptoms and should be limited; no significant food-drug interactions but high-fat meals may delay absorption. |
Loading safety data…
| Omeprazole is excreted into breast milk in low concentrations; estimated infant dose is <7% of maternal weight-adjusted dose. Not expected to cause adverse effects in infants; compatible with breastfeeding. |
| Lactation Rating | L2 (Probably Compatible) |
| Teratogenic Risk | In the first trimester, epidemiological studies do not consistently demonstrate a significantly increased risk of major congenital anomalies, though some studies suggest a small increased risk of specific defects such as cardiac malformations. No clear teratogenic risk in second or third trimesters; use only if clearly needed. |
| Fetal Monitoring | No specific monitoring required beyond routine prenatal care. Monitor for maternal gastrointestinal effects if used long-term. |
| Fertility Effects | No known significant effect on fertility in humans; limited animal data show no impairment of fertility at clinically relevant doses. |
| Clinical Pearls | Administer before the first meal of the day for maximal efficacy in acid suppression; inhibits CYP2C19 and may increase levels of clopidogrel, citalopram, and methotrexate; long-term use (>1 year) increases risk of osteoporosis-related fractures, hypomagnesemia, and vitamin B12 deficiency; do not break or crush delayed-release capsules; IV formulation is available for patients unable to take oral. |
| Patient Advice | Take omeprazole at least 30-60 minutes before a meal, preferably before breakfast. · Swallow the capsule whole; do not crush, chew, or open it. · If you have trouble swallowing, the capsule can be opened and the contents mixed with applesauce; take immediately. · Do not use for immediate relief of heartburn; it may take 1-4 days for full effect. · Long-term use may increase risk of bone fractures, low magnesium, or vitamin B12 deficiency; discuss with your doctor. · Avoid alcohol and NSAIDs (e.g., ibuprofen, naproxen) as they can irritate the stomach. · Report any severe diarrhea, rash, joint pain, or unusual bruising to your doctor. · Do not double the dose if you miss one; take the next dose at the usual time. |