Brands, Medical Use, Clinical Data
Drug Category
- Antihistamines
- Anti-Ulcer Agents
- Enzyme Inhibitors
- Proton-pump Inhibitors
Dosage Forms
- Tablet (delayed-release)
- Delayed-release capsules
- IV injection solution
- IV iufusion solution
Brands / Synonyms
Esomeprazole and Salts; Esomeprazole Magnesium; Esomeprazole Sodium; Esomperazole; Nexiam; Nexium; Nexium I.V.; Nexium Iv; Omeprazole; Prilosec; Vimovo; Zegerid
Indications
For the treatment of acid-reflux disorders (GERD) and peptic ulcer disease
Pharmacology
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 enzyme system at the secretory surface of the gastric parietal cell. Because this enzyme system is regarded as the acid (proton) pump within the gastric mucosa, Esomeprazole has been characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid production. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.
Mechanism of Action
Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. By acting specifically on the proton pump, Esomeprazole blocks the final step in acid production, thus reducing gastric acidity.
Absorption
90%
Toxicity
Blurred vision, confusion, drowsiness, dry mouthflushingheadache, nausea, rapid heartbeat, sweating
Biotrnasformation / Drug Metabolism
Hepatic
Contraindications
NEXIUM is contraindicated in patients with known hypersensitivity to any component of the formulation
or to substituted benzimidazoles.
Clarithromycin is contraindicated in patients with a known hypersensitivity to any macrolide
antibiotic.
Concomitant administration of clarithromycin with pimozide is contraindicated. There have been
post-marketing reports of drug interactions when clarithromycin and/or erythromycin are co-administered with pimozide
resulting in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsade de
pointes) most likely due to inhibition of hepatic metabolism of pimozide by erythromycin and clarithromycin.
Fatalities have been reported. (Please refer to full prescribing information for clarithromycin.)
Amoxicillin is contraindicated in patients with a known hypersensitivity to any penicillin. (Please
refer to full prescribing information for amoxicillin.)
Drug Interactions
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. Post-marketing reports of changes in prothrombin
measures have been received among patients on concomitant warfarin and esomeprazole therapy. Increases in INR and
prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and
warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.
Esomeprazole may potentially interfere with CYP2C19, the major esomeprazole metabolizing enzyme.
Coadministration of esomeprazole 30 mg and diazepam, a CYP2C19 substrate, resulted in a 45% decrease in clearance of
diazepam. Increased plasma levels of diazepam were observed 12 hours after dosing and onwards. However, at that time,
the plasma levels of diazepam were below the therapeutic interval, and thus this interaction is unlikely to be of
clinical relevance.
Esomeprazole inhibits gastric acid secretion. Therefore, esomeprazole may interfere with the
absorption of drugs where gastric pH is an important determinant of bioavailability (eg, ketoconazole, iron salts and
digoxin).
Coadministration of oral contraceptives, diazepam, phenytoin, or quinidine did 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.
Concomitant administration of clarithromycin with pimozide is contraindicated.
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