The P-I-E-N-O Parkinsn's List Drug Database
omeprazole / PrilosecTM , AstraTM
ANTI-ULCER:
Description: Omeprazole is an oral antiulcer agent. It is indicated for short term therapy of gastroesophageal reflux disease, gastric and duodenal ulcers, and gastric hypersecretory conditions including Zollinger-Ellison syndrome, systemic mastocytosis, and multiple endocrine adenoma. Unlike other antiulcer agents, omeprazole does not antagonize HA or cholinergic receptors. Omeprazole has a long duration of action and a high level of potency, allowing for once-daily administration. Although omeprazole is a potent drug, it must be used in combination with antibiotics to be effective against Helicobacter pylori. While there is concern regarding long-term use of omeprazole, in November 1994, a study was published documenting the superiority of maintenence therapy for 12 months with omeprazole over ranitidine in patients with reflux esophagitis. In December 1994, an FDA advisory committee recommended omeprazole be approved for maintenance therapy of healed erosive esophagitis. Investigations are currently underway to assess the efficacy of omeprazole in combination with either amoxicillin or clarithromycin for the treatment of peptic ulcer disease. Omeprazole was originally approved by the FDA in September 1989.
Mechanism of Action: Omeprazole belongs to a new class of antisecretory agents, the substituted benzimidazoles, which suppress gastric acid secretion by inhibiting the H+/K+ ATPase enzyme system of parietal cells. Following activation in an acidic pH, omeprazole binds irreversibly to the H+/K+ ATPase pump on the secretory surface of the parietal cell membrane. Subsequently, the secretion of hydrogen ions into the gastric lumen is inhibited. Omeprazole is characterized as a gastric acid pump inhibitor because it blocks the final step of gastric acid production. It inhibits both basal and stimulus-induced acid secretion. Omeprazole is an extremely potent drug. Intragastric pH of patients receiving omeprazole is often higher and affected longer than during therapy with HA-antagonists. Omeprazole is also more effective than either HA-antagonists or sucralfate in the treatment of gastroesophageal reflux disease (GERD).
Serum gastrin levels increase during the initial 1-2 weeks of therapy, and median increases in gastrin are greater than the increases produced by HA-receptor antagonists. Gastrin levels return to baseline within 1-2 weeks following discontinuance of therapy. Gastrin levels in patients with Zollinger-Ellison syndrome are not affected. Animal data suggest that prolonged elevations of serum gastrin may be associated with tumors. Finally, omeprazole also inhibits the hepatic cytochrome P-450 oxidase system (see Drug Interactions).
Pharmacokinetics: Omeprazole is administered orally and should be taken prior to meals, preferably in the morning. Omeprazole is enteric-coated, and absorption begins only after the granules have passed through the stomach. Due to a significant first-pass effect, bioavailability following oral doses of 20-40 mg is 3040%, but it may approach 100% in patients with hepatic impairment. The drug is rapidly absorbed following oral administration and distributes throughout the body tissues, concentrating in the gastric parietal cells. It is not known if it crosses the placenta or is excreted into breast milk (see Contraindications). The drug's onset of action is 1 hour, and the duration of inhibition is greater than 72 hours. Omeprazole is 95% bound to plasma proteins. Extensive hepatic metabolism occurs, and the metabolites have minimal antisecretory activity. The plasma half-life in healthy patients is 0.5-1 hour, while the half-life in patients with chronic hepatic disease is approximately 3 hours. Secretory activity returns to normal 3-5 days after therapy is discontinued. Approximately 72-80% of a dose is excreted renally, and 18-23% is excreted in the feces.
CONTRAINDICATIONS/PRECAUTIONS: Omeprazole is classified as pregnancy category C. It is not known whether this drug crosses the placenta or is excreted into breast milk. Omeprazole should be used during pregnancy or breast-feeding only when clearly needed.
Omeprazole should be administered with caution to patients with hepatic disease since clearance of the drug can be prolonged. Dosage adjustments, however, are generally not needed. In addition, omeprazole has been associated with hepatitis and, in rare instances, hepatic failure.
Omeprazole decreases intragastric acidity. Subsequently, the number of bacteria in gastric secretions and, correspondingly, the amount of carcinogenic N-nitroso compounds produced by these bacteria increase. Long-term results of clinical studies involving patients with Zollinger-Ellison syndrome have shown a small increase in risk for gastric carcinomas. Another trial studied 25 patients with HA-receptor antagonist-resistant gastroesophageal reflux disease (GERD) who were treated and then followed on long-term (" 4 years) omeprazole therapy. Neoplasia or dysplasia were not seen in biopsies.D Also, it recently has been shown that omeprazole can cause malabsorption of vitamin B (see Adverse Reactions).
DRUG INTERACTIONS: Omeprazole can exhibit a dose-dependent inhibition of the hepatic cytochrome P-450 enzyme system. Because of this, omeprazole can decrease the metabolism of drugs metabolized via this pathway, resulting in increased plasma concentrations. Examples of drugs that may be affected by omeprazole include diazepam, phenytoin, and warfarin. Other agents that are metabolized via the cytochrome P-450 system can be similarly affected. While the interaction between omeprazole and diazepam has been reported several times, other benzodiazepines are less well studied. Patients should be monitored carefully for signs of increased drug effect if omeprazole is used with other benzodiazepines metabolized via hepatic oxidation or in any patient receiving phenytoin or warfarin.
Omeprazole increases the pH of the stomach. This increase in intragastric pH can interfere with the absorption of ampicillin administered in ester form, iron salts, or ketoconazole. Changes in intragastric pH can potentially alter the bioavailability of other drugs with pH-dependent absorption. It recently has been shown than omeprazole can impair absorption of vitamin B (see Adverse Reactions).
A case report of a patient with delayed methotrexate elimination while taking omeprazole that did not occur during subsequent methotrexate cycles in the absence of omeprazole has implied a drug interaction. Methotrexate undergoes active tubular secretion in the kidney and omeprazole may interfere with renal ATPase. Although the patient was not rechallenged with omeprazole, omeprazole should be used cautiously in patients receiving high-dose methotrexate.
ADVERSE REACTIONS: Few adverse effects have been associated with omeprazole. Headache has been reported in 6.9% of patients. Frequently reported gastrointestinal disturbances include diarrhea (3%) and constipation (1.1%). Other GI effects, such as abdominal pain and nausea/vomiting, may not be statistically significant when compared with placebo.
In rare instances, hematologic abnormalities have been reported during omeprazole therapy (<1%) and warrant medical attention. These effects include pancytopenia, hemolysis with anemia, leukocytosis, neutropenia, and thrombocytopenia. In a study of healthy volunteers, it was shown that omeprazole caused a significant reduction in cyanocobalamin (vitamin BAA) absorption. Since neurologic manifestations can appear in the absence of hematologic changes, patients should be monitored for signs of pernicious anemia.
Hepatitis has been reported in fewer than 1% of patients receiving omeprazole. In rare instances, hepatic failure has occurred. Elevated hepatic enzymes (SGPT, SGOT, alkaline phosphatase), and jaundice also have been observed.
Animal and human data have demonstrated a proliferation of enterochromaffin-like cells due to hypergastrinemia, which may be associated with the development of malignant gastric carcinoma during long-term administration of omeprazole. Recently, new data suggest omeprazole may be given for as long as 5 years without concern for the development of gastric neoplasia. Twenty-five patients with HA-receptor antagonistresistant gastroesophageal reflux disease (GERD) were treated and then followed on long-term (" 4 years) omeprazole therapy. A significant increase of micronodular hyperplasia, subatrophic gastritis, and atrophic gastritis was reported. Persistent increases in median gastrin concentrations were noted during treatment; concentrations did not significantly increase during maintenance therapy. A subgroup of patients with very high gastrin concentrations (> 500 ng/L) had a higher incidence of enterochromaffin-like cell hyperplasia than did other patients. Neoplasia or dysplasia were not seen in biopsies, however. If long-term therapy with omeprazole is needed, continued histopathologic monitoring is needed.
PATIENT INFORMATION:
What do omeprazole capsules do?
Omeprazole (PrilosecTM ) prevents the production of acid in the stomach. It reduces symptoms and prevents injury to the esophagus, stomach, or intestines in patients with gastroesophageal reflux disease (GERD) or ulcers. Omeprazole is also useful in conditions that cause excessive stomach acid production such as Zollinger-Ellison syndrome and certain cancers. Generic omeprazole capsules are not yet available.
What should my doctor, dentist, or pharmacist know before I take omeprazole?
They need to know if you have any of these conditions:
How should I take this medicine?
Take omeprazole capsules by mouth. Follow the directions on the prescription label. Swallow the capsules whole with a drink of water; do not crush or chew. Omeprazole works best if taken on an empty stomach. It is best to take the capsules 30 to 60 minutes before breakfast. Take your doses at regular intervals. Do not take your medicine more often than directed.
Special precautions for use in children:
This medicine is not for use in children.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.
What other medicines can interact with omeprazole?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking omeprazole?
Serious side effects are rare, occurring in 1% or fewer of patients, they include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with omeprazole include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take omeprazole?
It can take several days of therapy with omeprazole before your stomach pains improve. Check with your doctor if your condition does not improve, or if it gets worse. You can take antacids for the occasional relief of pain unless your doctor tells you otherwise.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15 and 30C (59 and 86F). Protect from light and moisture. Throw away any unused medicine after the expiration date.
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