INEXIUM

Esomeprazole, sold under the brand name Nexium, is a proton pump inhibitor (PPI) medication used for the management of gastroesophageal reflux disease (GERD), for gastric protection to prevent recurrence of stomach ulcers or gastric damage from chronic use of NSAIDs, and for the treatment of pathological hypersecretory conditions including Zollinger-Ellison (ZE) Syndrome.

It can also be found in quadruple regimens for the treatment of H. pylori infections along with other antibiotics including Amoxicillin, Clarithromycin, and Metronidazole, for example. 7, 10 Its efficacy is considered similar to other medications within the PPI class including Omeprazole, Pantoprazole, Lansoprazole, Dexlansoprazole, and Rabeprazole.

Esomeprazole is the s-isomer of

Omeprazole, which is a racemate of the S.

Esomeprazole has been shown to inhibit acid secretion to a similar extent as Omeprazole, without any significant differences between the two compounds in vitro.

Esomeprazole exerts its stomach acid-suppressing effects by preventing the final step in gastric acid production by covalently binding to sulfhydryl groups of cysteines found on the (H+, K+)-ATPase enzyme at the secretory surface of gastric parietal cells.

This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus.

As the binding of esomeprazole to the (H+, K+)-ATPase enzyme is irreversible and new enzyme needs to be expressed in order to resume acid secretion, esomeprazole's duration of antisecretory effect persists longer than 24 hours.

PPIs such as esomeprazole have also been shown to inhibit the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme necessary for cardiovascular health.

DDAH inhibition causes a consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginie (ADMA), which is thought to cause the association of PPIs with increased risk of cardiovascular events in patients with unstable coronary syndromes. 3, 4 Due to their good safety profile and as several PPIs are available over the counter without a prescription, their current use in North America is widespread.

Long term use of

PPIs such as esomeprazole has been associated with possible adverse effects, however, including increased susceptibility to bacterial infections (including gastrointestinal C. difficile ), reduced absorption of micronutrients such as iron and B12, and an increased risk of developing hypomagnesemia and hypocalcemia which may contribute to osteoporosis and bone fractures later in life.

Rapid discontinuation of

PPIs such as esomeprazole may cause a rebound effect and a short term increase in hypersecretion.

Esomeprazole doses should be slowly lowered, or tapered, before discontinuing to prevent this rebound effect.

Esomeprazole is indicated for the treatment of acid-reflux disorders including healing and maintenance of erosive esophagitis, and symptomatic gastroesophageal reflux disease (GERD), peptic ulcer disease, H. pylori eradication, prevention of gastrointestinal bleeds with NSAID use, and for the long-term treatment of pathological hypersecretory conditions including Zollinger-Ellison Syndrome.

Esomeprazole is a compound that inhibits gastric acid secretion and is indicated in the treatment of gastroesophageal reflux disease (GERD), the healing of erosive esophagitis, and H. pylori eradication to reduce the risk of duodenal ulcer recurrence.

Esomeprazole belongs to a new class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or H2 histamine antagonistic properties, but that suppress gastric acid secretion by specific inhibition of the H + /K + ATPase at the secretory surface of the gastric parietal cell.

By doing so, it inhibits acid secretion into the gsatric lumen.

This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.

Esomeprazole is the s-isomer of

Omeprazole, which is a racemate of the S.

Esomeprazole has been shown to inhibit acid secretion to a similar extent as Omeprazole, without any significant differences between the two compounds in vitro.

PPIs such as esomeprazole have also been shown to inhibit the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme necessary for cardiovascular health.

DDAH inhibition causes a consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginie (ADMA), which is thought to cause the association of PPIs with increased risk of cardiovascular events in patients with unstable coronary syndromes. 3, 4 Due to their good safety profile and as several PPIs are available over the counter without a prescription, their current use in North America is widespread.

Long term use of

PPIs such as esomeprazole has been associated with possible adverse effects, however, including increased susceptibility to bacterial infections (including gastrointestinal C. difficile ), reduced absorption of micronutrients including iron and B12, and an increased risk of developing hypomagnesemia and hypocalcemia which may contribute to osteoporosis and bone fractures later in life.

After oral administration, peak plasma levels (Cmax) occur at approximately 1.5 hours (Tmax).

Cmax increases proportionally when the dose is increased, and there is a three-fold increase in the area under the plasma concentration-time curve (AUC) from 20-40 mg.

AUC after administration of a single 40 mg dose of Esomeprazole is decreased by 43% to 53% after food intake compared to fasting conditions.

Esomeprazole should be taken at least one hour before meals.

Esomeprazole magnesium 40 mg once daily was given in combination with Clarithromycin 500 mg twice daily and Amoxicillin 1000 mg twice daily for 7 days to 17 healthy male and female subjects.

The mean steady state AUC and

Cmax of esomeprazole increased by 70% and 18%, respectively during triple combination therapy compared to treatment with esomeprazole alone.

The observed increase in esomeprazole exposure during co-administration with clarithromycin and amoxicillin is not expected to produce significant safety concerns.

The apparent volume of distribution at steady state in healthy volunteers is approximately 16 L.

Esomeprazole is extensively metabolized in the liver by the cytochrome P450 (CYP) enzyme system.

The metabolites of esomeprazole lack antisecretory activity.

The major part of esomeprazole's metabolism is dependent upon the CYP2C19 isoenzyme, which forms the hydroxy and desmethyl metabolites.

The remaining amount is dependent on

CYP3A4 which forms the sulphone metabolite.

CYP2C19 isoenzyme exhibits polymorphism in the metabolism of esomeprazole, since some 3% of Caucasians and 15-20% of Asians lack CYP2C19 and are termed Poor Metabolizers.

However, the influence of CYP 2C19 polymorphism is less pronounced for esomeprazole than for omeprazole.

At steady state, the ratio of AUC in Poor Metabolizers to AUC in the rest of the population (Extensive Metabolizers) is approximately 2.

Following administration of equimolar doses, the S.

• and R-isomers are metabolized differently by the liver, resulting in higher plasma levels of the S.

• than of the R-isomer.

Nine major urinary metabolites have been detected.

The two main metabolites have been identified as hydroxyesomeprazole and the corresponding carboxylic acid.

Three major metabolites have been identified in plasma: the 5-O-desmethyl.

• and sulphone derivatives and hydroxyesomeprazole.

The major metabolites of esomeprazole have no effect on gastric acid secretion.

Hover over products below to view reaction partners Esomeprazole 5-hydroxyesomeprazole Active Metabolite of Esomeprazole Omeprazole sulfone 5-O-Desmethylomeprazole.

The plasma elimination half-life of esomeprazole is approximately 1-1.5 hours.

Less than 1% of parent drug is excreted in the urine.

Approximately 80% of an oral dose of esomeprazole is excreted as inactive metabolites in the urine, and the remainder is found as inactive metabolites in the feces.

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Blurred vision, confusion, drowsiness, dry mouth, flushing headache, nausea, rapid heartbeat, sweating.

Allergy alert

Do not use if you are allergic to esomeprazole.

Esomeprazole may cause severe skin reactions.

Symptoms may include: skin reddening blisters rash If an allergic reaction occurs, stop use and seek medical help right away.

Directions adults 18 years of age and older this product is to be used once a day (every 24 hours), every day for 14 days may take to 4 days for full effect 14-Day Course of Treatment.

• swallow 1 tablet with a glass of water before eating in the morning.

• take every day for 14 days.

• do not take more than 1 tablet a day.

• swallow whole.

Do not crush or chew capsules.

• do not use for more than 14 days unless directed by your doctor Repeated 14-Day Courses (if needed).

• you may repeat a 14-day course every 4 months.

• do not take for more than 14 days or more often than every 4 months unless directed by a doctor children under 18 years of age: ask a doctor before use.

Heartburn in children may sometimes be caused by a serious condition.