NEXIUM 24HR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NEXIUM 24HR (NEXIUM 24HR).
Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+ ATPase enzyme system at the secretory surface of gastric parietal cells. It is a weak base that accumulates in the acidic environment of the parietal cell canaliculus, where it is protonated and converted to the active achiral sulfenamide form, which forms a covalent disulfide bond with cysteine residues of the H+/K+ ATPase, irreversibly inhibiting the pump.
| Metabolism | Esomeprazole is extensively metabolized in the liver via the cytochrome P450 system, primarily by CYP2C19 and CYP3A4. The major metabolites are hydroxyl and desmethyl metabolites, which have no significant antisecretory activity. Metabolism is saturable, and systemic exposure is higher in poor metabolizers of CYP2C19. |
| Excretion | Approximately 77% of a single oral dose is excreted in urine as metabolites (primarily hydroxy- and desmethyl-omeprazole) and glucuronide conjugates, with less than 1% as unchanged drug. About 19% is eliminated in feces via biliary excretion. Renal clearance accounts for the majority of elimination. |
| Half-life | The terminal elimination half-life is approximately 1-2 hours in healthy individuals. However, the pharmacodynamic effect (acid suppression) lasts longer due to accumulation in the parietal cell canaliculus and irreversible binding to the proton pump. In poor CYP2C19 metabolizers, half-life may extend to 3-4 hours. |
| Protein binding | Esomeprazole is approximately 97% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | The apparent volume of distribution in healthy subjects is approximately 0.22 L/kg, indicating moderate distribution into body water. After repeated dosing, steady-state volume of distribution is about 0.25 L/kg. |
| Bioavailability | Oral bioavailability of esomeprazole is approximately 64% after a single 40 mg dose, increasing to 89% with repeated once-daily dosing due to decreased first-pass metabolism. Intravenous bioavailability is 100%. |
| Onset of Action | Oral (capsule or tablet): Onset of acid suppression occurs within 1 hour, with maximal effect after 2-4 days of once-daily dosing. Intravenous (esomeprazole): Onset of acid suppression occurs within 30 minutes. |
| Duration of Action | The duration of acid suppression after a single oral dose is approximately 24 hours, but full inhibition of gastric acid secretion may persist for up to 72 hours due to irreversible binding to the proton pump. Repeated once-daily dosing leads to sustained acid control. |
20 mg orally once daily for 14 days for frequent heartburn; for gastroesophageal reflux disease (GERD), 20 mg orally once daily for 4-8 weeks; for erosive esophagitis, 20-40 mg orally once daily for 4-8 weeks.
| Dosage form | CAPSULE, DELAYED RELEASE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. For severe renal impairment (CrCl <30 mL/min), maximum dose is 20 mg daily. |
| Liver impairment | For mild to moderate hepatic impairment (Child-Pugh A or B), maximum dose is 20 mg daily. For severe hepatic impairment (Child-Pugh C), use with caution; maximum dose is 20 mg daily. |
| Pediatric use | For GERD in children 1-11 years: weight 5-<20 kg: 10 mg once daily for up to 8 weeks; weight ≥20 kg: 20 mg once daily for up to 8 weeks. For adolescents 12-17 years: 20 mg once daily for up to 8 weeks for GERD; for erosive esophagitis, 20 mg once daily for 4-8 weeks. |
| Geriatric use | No dose adjustment required in elderly patients. However, long-term use may increase risk of osteoporosis-related fractures, Clostridium difficile infection, and vitamin B12 deficiency. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NEXIUM 24HR (NEXIUM 24HR).
| Breastfeeding | Excreted in breast milk; M/P ratio approximately 0.50. Use caution; consider risk:benefit. American Academy of Pediatrics considers compatible. |
| Teratogenic Risk | Category C: First trimester no increased risk from human data; second/third trimester avoid unless necessary due to possible fetal acidosis from maternal acid suppression. Animal studies show no teratogenicity at doses up to 40 mg/kg/day. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to esomeprazole, other benzimidazoles (e.g., omeprazole, pantoprazole), or any component of the formulation","Co-administration with rilpivirine","Co-administration with atazanavir (due to reduced atazanavir absorption)"]
| Precautions | ["Acute interstitial nephritis","Clostridium difficile-associated diarrhea (CDAD)","Bone fracture risk (hip, wrist, spine) associated with long-term use","Cutaneous lupus erythematosus and systemic lupus erythematosus","Cyanocobalamin (vitamin B12) deficiency with long-term use","Hypomagnesemia, symptomatic and asymptomatic, with prolonged use","Increased risk of fundic gland polyps with long-term use","Interaction with clopidogrel (reduced antiplatelet effect)","Potential for false positive urine tetrahydrocannabinol (THC) screening tests","Atrophic gastritis (observed in long-term studies)"] |
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| Monitor maternal acid-related symptoms; no routine fetal monitoring needed. Assess renal and hepatic function if prolonged use. |
| Fertility Effects | No significant effect on fertility in animal studies; human data limited. Unlikely to impair fertility at therapeutic doses. |