Products
Omeprazole is commercially available in tablet, capsule, and injection/infusion forms and has been approved in many countries since 1988. In addition to the original Antramups, generics and the -enantiomer esomeprazole (Nexium) are also commercially available. At the end of March 2010, after pantoprazole, omeprazole was also approved for self-medication in many countries. In the United States, omeprazole has been available without prescription since 2003.
Structure and properties
Omeprazole (C17H19N3O3S, Mr = 345.4 g/mol) is a white powder that is very sparingly soluble in water. In drugs, it is also present in the form of the more water-soluble sodium or magnesium salts. It is a benzimidazole derivative and racemate. The -enantiomer esomeprazole is also marketed with success. Two structural elements are of particular importance. First, the pyridine nitrogen, which leads to accumulation in the acidic environment of the secretory tubules (canaliculi) of the occupational cells by protonation. And second, sulfoxide (S=O), which is activated by a rearrangement to sulfenamide and binds to cysteines of the proton pump, thus inactivating it.
Effects
Omeprazole (ATC A02BC01) reduces gastric acid secretion by inactivating the proton pump (H+/K+-ATPase) in the gastric vestibular cells irreversibly. It does not act locally in the lumen of the stomach but is absorbed in the intestine and travels to the vestibular cells via the systemic circulation. It is a prodrug and is converted from acid to its active form only in the canaliculi of the vestibular cells, where it binds covalently to the proton pump, inhibiting it. Omeprazole is acid labile and must be administered in enteric-coated dosage forms. The inhibition of gastric acid secretion is dose-dependent and, as with all proton pump inhibitors, the full effect occurs with a delay of approximately 4 days. Because of covalent binding, omeprazole is effective for much longer than its short half-life of less than 1 hour would suggest, and once-daily dosing is therefore sufficient in most patients.
Indications
Without a physician’s prescription, omeprazole is approved for short-term treatment of reflux symptoms (eg, stomach burning, acid regurgitation) in adults 18 years of age and older for 2 weeks. Under medical treatment, it is additionally used for peptic ulcers, reflux esophagitis, Zollinger-Ellison syndrome, and eradication of Helicobacter pylori along with antibiotics.
Dosage
In self-medication, the dosage is 10 mg or 20 mg once daily for a maximum of 2 weeks. If symptoms persist, a doctor should be consulted. Under medical treatment, the daily dose can be increased up to 120 mg daily; usual daily doses in adults are 20 or 40 mg. Only dosage forms with a special galenic (e.g., MUPS or MUT) are divisible.
Contraindications
- Hypersensitivity
Taking it in self-medication can mask serious conditions such as a stomach or intestinal ulcer, bleeding or malignancies such as stomach cancer. Therefore, the precautions must be followed carefully. If symptoms include weight loss, dysphagia, repeated vomiting or hematemesis, or a history of gastric ulcer, medical evaluation should be obtained. Full, comprehensive precautions can be found in the drug label.
Interactions
Omeprazole is metabolized by CYP2C19 and competitively inhibits the isoenzyme. It should therefore not be co-administered with clopidogrel because the prodrug clopidogrel is biotransformed to the active metabolite via CYP2C19. Together with omeprazole, the efficacy of clopidogrel may be reduced. Omeprazole may prolong the elimination of CYP2C19 substrates, such as the antiepileptic drugs diazepam and phenytoin, thereby increasing their adverse effects. Gastric acid is significant for the absorption of some drugs, for example, the antifungals ketoconazole, itraconazole, and the HIV protease inhibitor atazanavir. Because omeprazole reduces stomach acid, it may also decrease the absorption of these drugs. Full details of interactions can be found in the SmPC.
Adverse effects
The most commonly observed adverse effects include gastrointestinal symptoms such as diarrhea, constipation, abdominal pain, nausea, vomiting, and flatulence. Headache is also common.
