NEXIUM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NEXIUM (NEXIUM).
Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+ ATPase enzyme (proton pump) at the secretory surface of gastric parietal cells. It is the S-isomer of omeprazole and is a weak base that accumulates in the acidic environment of the parietal cell canaliculi, where it is converted to the active sulfenamide form that binds covalently to the proton pump, irreversibly inhibiting acid secretion.
| Metabolism | Extensively metabolized in the liver by cytochrome P450 enzymes, primarily CYP2C19 and CYP3A4. The metabolites are hydroxylated, demethylated, and sulfone-conjugated derivatives, and are inactive. Esomeprazole is a time-dependent inhibitor of CYP2C19. |
| Excretion | Primarily hepatic metabolism via CYP2C19 and CYP3A4; approximately 80% of metabolites excreted in urine, and the remainder in feces via biliary elimination. Less than 1% of unchanged drug is excreted in urine. |
| Half-life | Approximately 1–1.5 hours in extensive CYP2C19 metabolizers; in poor metabolizers, half-life can be prolonged to 2–3 hours. Clinically, the plasma half-life does not directly correlate with the duration of acid suppression due to prolonged binding to the proton pump. |
| Protein binding | 97% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 0.25 L/kg (range 0.18–0.38 L/kg), indicating distribution primarily into extracellular fluid and tissues. |
| Bioavailability | Oral: 90% after multiple doses; first-pass metabolism reduces absolute bioavailability to about 50–60%. IV: 100%. |
| Onset of Action | Oral: 1–4 hours for maximal acid suppression; IV: significant acid suppression within 30 minutes to 1 hour. |
| Duration of Action | Acid suppression persists for up to 24 hours after a single dose due to irreversible binding to the proton pump. However, full recovery of acid secretion requires synthesis of new proton pumps, which takes 2–3 days. |
20-40 mg orally once daily; IV: 20 mg once daily.
| Dosage form | CAPSULE, DELAYED REL PELLETS |
| Renal impairment | No adjustment required for mild to moderate renal impairment (GFR >=30 mL/min). For severe renal impairment (GFR <30 mL/min), maximum dose is 20 mg/day. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: maximum dose 20 mg/day; Child-Pugh Class C: maximum dose 20 mg/day. |
| Pediatric use | Children 1-11 years: 10 mg orally once daily for up to 8 weeks; children >=12 years: 20-40 mg orally once daily. |
| Geriatric use | No specific dose adjustment; consider lower starting dose (20 mg) due to reduced hepatic clearance; monitor for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NEXIUM (NEXIUM).
| Breastfeeding | Esomeprazole is excreted in human milk in low amounts; the estimated infant dose is less than 1% of the maternal weight-adjusted dose. The milk-to-plasma ratio is approximately 0.1. It is generally considered compatible with breastfeeding due to low oral bioavailability and rapid clearance in infants. |
| Teratogenic Risk | In the first trimester, esomeprazole has not been associated with an increased risk of major congenital malformations based on observational studies with limited sample sizes. In the second and third trimesters, no fetal risks have been identified, but published data are insufficient to exclude a risk. Human data do not indicate fetotoxicity at therapeutic doses. |
■ FDA Black Box Warning
None
| Serious Effects |
1. History of hypersensitivity to esomeprazole, omeprazole, or any component of the formulation. 2. Concomitant use with rilpivirine-containing products. 3. Use of esomeprazole in patients receiving methotrexate (especially high-dose) may increase methotrexate toxicity. 4. Use with St. John's wort or rifampin may reduce efficacy. 5. Caution with clopidogrel due to potential interaction; avoid concomitant use if possible.
| Precautions | 1. Increased risk of Clostridium difficile-associated diarrhea. 2. Increased risk of osteoporosis-related fractures (hip, wrist, spine) with high-dose or long-term use. 3. Hypomagnesemia with prolonged use; monitor magnesium levels. 4. Vitamin B12 deficiency with long-term use (≥3 years). 5. Acute interstitial nephritis; discontinue if suspected. 6. Cutaneous lupus erythematosus and systemic lupus erythematosus. 7. Interaction with methotrexate; monitor for toxicity. 8. Atrophic gastritis with long-term use. 9. Cyanocobalamin absorption may be reduced. 10. May mask symptoms of gastric malignancy. |
Loading safety data…
| Fetal Monitoring | No specific maternal or fetal monitoring beyond routine prenatal care is required. However, use during pregnancy should be at the lowest effective dose for the shortest duration. |
| Fertility Effects | Animal studies have not shown impairment of fertility at esomeprazole doses up to 75 mg/kg/day (about 35 times the human dose). No human data on fertility effects are available. |