OMESK (Omeprazole delayed release USP 20mg)
The active ingredient in OMEPRAZOLE capsules are substituted benzimidazole, 5-methoxy 2[[(4methoxy-3, 5-dimethyl-2-pyridinyl)methyl]sulfinyl] 1H-benzimidazole, a compound that inhibits gastric acid secretion. Its empirical formula is C17H19N3O3S, with a molecular weight of 345.42. Omeprazole is a white to off-white crystalline powder which melts with decomposition at about 155°c. It is a weak base, freely soluble in ethanol and methanol, and slightly soluble in acetone and isopropanol and very slightly soluble in water. The stability of Omeprazole is a function of pH; it is rapidly degraded in acid media, but has acceptable stability under alkaline conditions.
Mechanism of action.
Omeprazole belongs to a new class of anti-secretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or H2 Histamine antagonistic properties, but that suppress gastric acid secretion by specific inhibition of H+/K+ATPase enzyme system at the secretory surface of the gastric parietal cells. Because this enzyme system is regarded as the acid (proton) pump within the gastric mucosa, omeprazole has been characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid secretion irrespective of the stimulus. Animal studies indicate that after rapid disappearance from plasma, omeprazole can be found within the gastric mucosa for a day or more.
After oral administration, the onset of the anti-secretory effect of omeprazole occurs within one hour, with the maximum effect occuring within two hours. Inhibition of secretion is about 50% of a maximum at 24 hours and the duration of inhibition lasts up to 72 hours. The anti-secretory effect thus lasts far longer than would be expected from the very short (less than one hour) plasma half-life, apparently due to prolonged binding to the parietal H+/K+ATPase enzyme. When the drug is discontinued, secretary activity returns gradually, over 3 to 5 days. The inhibitory effect of omeprazole on acid secretion increases with repeated once daily dosing, reaching a plateau after 4 days.
Indications and usage
Duodenal ulcer: Omeprazole capsules are indicated for short-term treatment of active duodenal ulcer. Most patients heal within four weeks. Some patients may require an additional four weeks of therapy.
Treatment of gastroesophageal reflux disease (GERD) symptomatic gerd: Omeprazole capsules are indicated for the treatment of heartburn and other symptoms associated with gerd.
Erosive esophagitis: Omeprazole capsules are indicated for the short term treatment (4 to 8 weeks) of erosive esophagitis which has been diagnosed by endoscopy. The efficacy of omeprazole used for longer than 8 weeks in these patients has not been established. In the rare instances of a patient not responding to 8 weeks of treatment, it may be helpful to give up to an additional 4 weeks of treatment. If there is a recurrence of erosive esophagitis or gerd symptoms (e.g. heartburn), additional 4-8 weeks courses of omeprazole may be considered.
Maintenance of healing of erosive esophagitis: Omeprazole capsules are indicated to maintain healing of erosive esophagitis. Controlled studies do not extend beyond 12 months.
Pathological hyper-secretory conditions: Omeprazole capsules are indicated for the long term treatment of pathological hyper-secretory conditions (e.g. Zollinger-Ellison syndrome, multiple endocrine adenomas and systemic mastocytosis)
Omeprazole capsules are contraindicated in patients with known hypersensitivity to any component of the formulation.
General symptomatic response to therapy with omeprazole does not preclude the presence of gastric malignancy. Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patient treated long-term with omeprazole. Information for patients omeprazole capsules should be taken before eating. Patients should be cautioned that the omeprazole capsules should not be opened, chewed or crushed, and should be swallowed whole.
Omeprazole can prolong the elimination of diazepam, warfarin and phenytoin, drugs that are metabolized by oxidation in the liver. Although in normal subjects no interaction with theophylline or propranolol was found, there have been clinical reports of interaction with other drugs metabolized via the cytochrome P-450 system (e.g. cyclosporin, disulfiram, benzidiazepines).
Patients should be monitored to determine if it is necessary to adjust the dosage of these drugs when taken concomitantly with omeprazole capsules. Because of its profound and long-lasting inhibition of gastric acid secretion, it is theoretically possible that omeprazole may interfere with absorption of drugs where gastric pH is an important determinant of their bioavailability (e.g. ketoconazole, ampicillin esters and iron salts)
Teratology studies conducted in pregnant rats at doses up to 138mg/kg/day (approximately 172 times the human dose) did not disclose any evidence for a teratogenic potential of omeprazole.
It is nor known whether omeprazole is excreted in human milk. In rats omeprazole administration during late gestation and lactation at doses of 13.8 to 138mg/kg/day (3.4 to 34 times the human dose) resulted in decreased weight gain pups. Because many drugs are excreted in human milk, because of the potential for serious adverse reaction in nursing infants from omeprazole and because of the potential for tumorgenicity shown for omeprazole in rat carcinogenicity studies 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.
Paediatric use: Safety and effectiveness in children have not been established.
Omeprazole capsules were generally well-tolerated during domestic and international clinical trials in patients. In the US, clinical trial patients (including duodenal ulcer, Zollinger-Ellison syndrome and resistant ulcer patients), the following adverse experiences were reported to occur in 1% or more of patients on therapy with Omeprazole capsules.
Numbers in parentheses indicate percentages of the adverse experiences considered by investigators as possibly, probably or definitely to the drug.