It is indicated for the treatment of - Gastroesophageal Reflux Disease (GERD), Healing of Erosive Esophagitis, Maintenance of healing of Erosive Esophagitis, Symptomatic Gastroesophageal Reflux Disease (GERD), Risk Reduction of NSAID associated gastric ulcer & H. pylori eradication (Triple therapy).
Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. Esomeprazole (S-isomer of omeprazole) is the first single optical isomer of proton pump inhibitor, provides better acid control than racemic proton pump inhibitors.
Absorption: Esomeprazole capsules contain an enteric-coated pellet formulation of esomeprazole magnesium. After oral administration peak plasma levels (Cmax) occur at approximately 1.5 hours (Tmax). The 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 to 40 mg. At repeated once daily dosing, the systemic bioavailability is approximately 90% compared to 64% after a single dose. The AUC after administration of a single dose of esomeprazole is decreased by 33-53% after food intake compared to fasting conditions. Esomeprazole should be taken at least one hour before meals.
Distribution: Esomeprazole is 97% bound to plasma proteins. Plasma protein binding is constant over the concentration range of 2 20 mmol/L. The apparent volume of distribution at steady state in healthy volunteers is approximately 16 L.
Metabolism: Esomeprazole is extensively metabolized in the liver by the cytochrome P450 (CYP) enzyme system. The metabolites of esomeprazole lack anti-secretory 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.
Excretion: 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 faeces.
Combination Therapy with Antimicrobials: Esomeprazole magnesium 40 mg once daily is given in combination with clarithromycin 500 mg twice daily and amoxicillin 1000 mg twice daily for 7 days. 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 pharmacokinetic parameters for clarithromycin and amoxicillin are similar during triple combination therapy and administration of each drug alone. However, the mean AUC and Cmax for 14-hydroxyclarithromycin are increased by 19% and 22%, respectively, during triple combination therapy compared to treatment with clarithromycin alone. This increase in exposure to 14-hydroxyclarithromycin is not considered to be clinically significant.
Adult : PO Erosive oesophagitis 40 mg once daily for 4 wk, up to another 4 wk if needed. Maintenance: 20 mg once daily. GERD 40 mg once daily for 4 wk, up to another 4 wk if needed. Maintenance or GERD w/o erosive oesophagitis: 20 mg once daily. Peptic ulcer 20 mg bid for 7 days or 40 mg once daily for 10 days as triple therapy w/ amoxicillin and clarithromycin. Prophylaxis of NSAID-induced ulcers 20 or 40 mg/day. NSAID-associated ulceration 20 mg once daily for 4-8 wk. Zollinger-Ellison syndrome Initial: 40 mg bid. Usual range: 80-160 mg/day. Daily doses >80 mg should be given in 2 divided doses. IV GERD 20 or 40 mg by inj over at least 3 min or infusion over 10-30 min once daily for ≤10 days until PO can be resumed. NSAID-associated ulceration 20 mg/day by inj over at least 3 min or infusion over 10-30 min until PO can be resumed. Gastric and duodenal ulcers 80 mg infusion over 30 min followed by continuous infusion 8 mg/hr over 72 hr, until PO can be resumed given as 40 mg once daily for 4 wk. Delayed-Release Cap: Should be taken on an empty stomach. Take 1 hr before meals. Tab: May be taken with or without food.
Esomeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. In vitro and in vivo studies have shown that Esomeprazole is not likely to inhibit CYPs 1A2, 2A6, 2C9, 2D6, 2E1 and 3A4. No clinically relevant interactions with drugs metabolized by these CYP enzymes would be expected. Drug interaction studies have shown that Esomeprazole does not have any clinically significant interactions with phenytoin, warfarin, quinidine, clarithromycin or amoxicillin.
Esomeprazole may potentially interfere with CYP2C19, the major Esomeprazole metabolizing enzyme. Co-administration of Esomeprazole 30 mg and diazepam, a CYP2C19 substrate has resulted in a 45% decrease in clearance of diazepam. Increased plasma levels of diazepam have been observed 12 hours after dosing and onwards. Esomeprazole inhibits gastric acid secretion. Therefore, Esomeprazole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (e.g., ketoconazole, iron salts and digoxin).
Co-administration of oral contraceptives, diazepam, phenytoin, or quinidine do not seem to change the pharmacokinetic profile of Esomeprazole.
Combination Therapy with Clarithromycin: Co-administration of esomeprazole, clarithromycin, and amoxicillin has resulted in increases in the plasma levels of esomeprazole and 14-hydroxyclarithromycin.
Esomeprazole is contraindicated in those patients who have known hypersensitivity to any other components of the formulation. Exclude the possibility of malignancy when gastric ulcer is suspected & before treatment for dyspepsia.
Side Effects reported with Esomeprazole include headache, diarrhea & abdominal pain.
This drug should be used during regnancy only if clearly needed. Because Esomeprazole is likely to be excreted in human milk, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
A single oral dose of Esomeprazole at 510 mg/kg (about 103 times the human dose on a body surface area basis), has been lethal to rats. The major signs of acute toxicity are reduced motor activity, changes in respiratory frequency, tremor, ataxia, and intermittent clonic convulsions. There have been no reports of overdose with Esomeprazole. No specific antidote for Esomeprazole is known. Since Esomeprazole is extensively protein bound, it is not expected to be removed by dialysis. In the event of overdosage, treatment should be symptomatic and supportive. As with the management of any overdose, the possibility of multiple drug ingestion should be considered.
Store at a temperature not exceeding 30°C in a dry place. Protect from light and moisture. Keep out of reach of children.
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