Nexium I.V. (esomeprazole sodium)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Esomeprazole, commonly referred to as an acid- or proton-pump inhibitor, is a gastric antisecretory agent. Esomeprazole is the S-isomer of omeprazole.
Esomeprazole, a proton-pump inhibitor (PPI), belongs to the class of substituted benzimidazoles that are gastric antisecretory agents. Esomeprazole is the S-isomer of omeprazole, which is a racemic mixture of R- and S-isomers.
Esomeprazole binds to hydrogen-potassium ATPase in gastric parietal cells; inactivation of this enzyme system (also known as the proton, hydrogen, or acid pump) blocks the final step in the secretion of hydrochloric acid by these cells, inhibiting gastric acid secretion.
Because the esomeprazole molecule is acid labile, the commercially available delayed-release capsules and packets for delayed-release oral suspension contain enteric-coated granules of the drug to increase oral bioavailability. Esomeprazole is extensively metabolized, principally by the hepatic cytochrome P-450 (CYP) 2C19 isoenzyme and to a lesser extent by CYP3A4. The CYP2C19 isoenzyme is polymorphically expressed; poor metabolizers (about 3% of Caucasians and 15-20% of Asians) lack the isoenzyme, and the metabolism of esomeprazole and omeprazole is decreased in such individuals compared with the rest of the population (i.e., extensive or rapid metabolizers).
At steady state, the ratio of AUC of esomeprazole in poor metabolizers compared to rapid metabolizers is about 2:1.
Increased gastric pH during esomeprazole therapy results in enterochromaffin-like cell (ECL) hyperplasia and increased serum Chromogranin A (CgA) levels. The prevalence of ECL hyperplasia increases with dose and duration of therapy. Although rats have demonstrated carcinoid lesions, no ECL cell carcinoids, dysplasia, or neoplasia have occurred to date in over 1000 patients receiving esomeprazole (10, 20, or 40 mg) for up to 1 year.
Additionally, human gastric biopsy specimens from adult and pediatric patients treated with omeprazole in long-term clinical trials did not detect ECL carcinoids, dysplasia, or neoplasia in any patient, although the incidence of ECL hyperplasia increased with time.
Following single dose administration of 40 mg, esomeprazole delayed-release capsules and esomeprazole granules for delayed-release suspension show similar bioavailability under fasting conditions. Administration of a 40-mg delayed-release capsule with food decreases the AUC by 43-53%. Peak plasma levels of esomeprazole occur in about 1.5 hours after oral administration.
Following single dose administration of 40 mg of oral esomeprazole, the bioavailability is approximately 64% compared to 90% with repeated once-daily dosing.
Esomeprazole is 97% bound to human plasma proteins. Esomeprazole undergoes extensive metabolism in the liver by CYP enzymes. Metabolites of esomeprazole lack antisecretory activity.
Esomeprazole is a time-dependent inhibitor of CYP2C19, resulting in autoinhibition and nonlinear pharmacokinetics. The elimination half-life of oral esomeprazole is approximately 1-1.5 hours. The elimination half-life of IV esomeprazole is approximately 1.1-1.4 hours, and is prolonged with increases in dosage.
Less than 1% of active drug is excreted in the urine, while 80% of an oral dose of esomeprazole is excreted as inactive metabolites in the urine, and the remainder as inactive metabolites in the feces.
The elimination half-life of esomeprazole following oral administration in infants 1-11 months of age is 0.9 hours, and ranges from 0.7-0.9 hours in children 1-11 years of age. In adolescents 12-17 years of age, the elimination half-life of oral esomeprazole is 0.8-1.2 hours. Following oral dosage of 40 mg once daily in patients with severe (Child-Pugh class C) hepatic impairment, steady-state AUCs are 2-3 times greater than those in patients with normal hepatic function.
Generic name: esomeprazole sodium
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Nexium I.V.
Indications
The following indications are listed for Nexium I.V.:
- Acute Duodenal Ulcer With Hemorrhage
- Acute Gastric Ulcer With Hemorrhage
- Erosive Esophagitis
- Reflux Esophagitis
Also known as: Acute Du With Hemorrhage, Acute Duodenal Ulcer With Bleeding, Acute Gastric Ulcer With Bleeding, Gastric Ulcer With Hemorrhage, Gastro-Esophageal Reflux Disease With Esophagitis.
Dosing
Dosage of esomeprazole magnesium or esomeprazole sodium is expressed in terms of esomeprazole.
Duration of therapy with a PPI should be based on safety and efficacy data associated with the specific indication, dosing frequency as described by the manufacturer, and the needs of individual patients. The potential benefits versus possible risks of initiating or continuing PPI therapy should be weighed carefully.
Esomeprazole magnesium is administered orally; commercially available as delayed-release capsules and delayed-release granules for oral suspension. A fixed-combination preparation containing naproxen and esomeprazole magnesium is also commercially available; see the full prescribing information for additional information.
Esomeprazole sodium is administered by IV injection or IV infusion; commercially available as a lyophilized powder in a single-dose vial for reconstitution prior to IV administration.
Esomeprazole is also available as over-the-counter (OTC) preparations used orally as self-medication for short-term treatment of frequent heartburn. See the manufacturer's Drug Facts for further information.
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No dosing information is available for this tab.
Drug interactions
Esomeprazole is extensively metabolized by the cytochrome P-450 (CYP) 2C19 isoenzyme and to a lesser extent by CYP3A4. Esomeprazole is a time-dependent inhibitor of CYP2C19, resulting in autoinhibition; in vitro and in vivostudies have shown that the medication is unlikely to inhibit CYP3A4, 1A2, 2A6, 2C9, 2D6, and 2E1.
Esomeprazole is an enantiomer of omeprazole; drug interactions with omeprazole may occur with esomeprazole.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Known hypersensitivity to esomeprazole or other substituted benzimidazoles (e.g., lansoprazole, omeprazole, pantoprazole, rabeprazole) or any ingredient in the formulation.
*Use with rilpivirine-containing products.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects occurring in 1% or more of patients receiving oral esomeprazole include headache, diarrhea, nausea, flatulence, abdominal pain, constipation, and dry mouth. Common adverse effects of IV esomeprazole generally are similar to those reported with oral esomeprazole, although injection site reaction, dizziness/vertigo, and pruritus also occur commonly with IV administration.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of oral esomeprazole for short-term (4-8 weeks) treatment of gastroesophageal reflux disease (GERD) in pediatric patients 1-17 years of age are supported by evidence from controlled clinical trials in adults and by safety and pharmacokinetic studies in children and adolescents. Safety and tolerability of oral esomeprazole 5, 10, or 20 mg daily for up to 8 weeks were evaluated in children 1-11 years of age with endoscopically diagnosed GERD; the presence or absence of erosive esophagitis was confirmed endoscopically in this study. Safety and tolerability of oral esomeprazole 20 or 40 mg daily for up to 8 weeks were evaluated in adolescents 12-17 years of age with clinically diagnosed GERD; the presence or absence of erosive esophagitis was not confirmed endoscopically in this study. Adverse effects reported in children and adolescents were similar to those reported during clinical trials in adults; however, a higher incidence of somnolence was reported in children.
Safety and efficacy of oral esomeprazole for short-term (up to 6 weeks) treatment of erosive esophagitis due to acid-mediated GERD in infants 1 month to less than 1 year of age are supported by controlled clinical trials in adults and by safety, pharmacokinetic, and pharmacodynamic studies in pediatric patients. The most commonly reported adverse effects in infants 1-11 months of age receiving oral esomeprazole include irritability and vomiting. Safety and efficacy of oral esomeprazole for other uses in pediatric patients have not been established. In a randomized, controlled, treatment-withdrawal study in infants 1-11 months of age with symptomatic GERD (diagnosed clinically in most patients), the proportion of patients discontinuing treatment because of worsening symptoms was similar in the esomeprazole and placebo groups.
Safety and efficacy of IV esomeprazole for short-term treatment of GERD with erosive esophagitis in pediatric patients 1 month to 17 years of age are supported by pharmacokinetic studies of IV esomeprazole in pediatric patients and adults and by pharmacodynamic studies of oral esomeprazole in pediatric patients and of IV esomeprazole in adults. Adverse effects of IV esomeprazole in pediatric patients 1 month to 17 years of age were consistent with the known safety profile.
Safety and efficacy of IV esomeprazole in neonates younger than 1 month of age have not been established.
Data are insufficient evaluating esomeprazole during pregnancy. Esomeprazole is the S-isomer of omeprazole, and epidemiologic data evaluating omeprazole use in the first trimester failed to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes. Reproductive studies in rats and rabbits demonstrated embryolethality that was dose-dependent at omeprazole doses ranging from 3.4-34 times the oral human dose of 40 mg (based on a body surface area for a 60-kg person).
It is unknown whether esomeprazole is distributed into milk. However, omeprazole is distributed into human milk. Effects of esomeprazole on the breast-fed child or on milk production are unknown.
Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for esomeprazole and any potential adverse effects on the breast-fed child from the medication or from the underlying maternal condition.
The manufacturer makes no specific dosage recommendations for oral or IV esomeprazole in geriatric patients.
No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity of some older patients cannot be ruled out.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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