Proton Pump Inhibitor
Omeprazole is a substituted benzimidazole which suppresses gastric acid secretion. Omeprazole is activated at an acidic pH to a sulphenamide derivative that binds irreversibly to H+/K+ ATPase, an enzyme system found at the secretory surface of parietal cells. It hereby inhibits the final transport of hydrogen ions to the gastric lumen. Therefore, Omeprazole has been referred to as an acid or proton pump inhibitor. Omeprazole inhibits basal and stimulated gastric acid secretion. The degree of inhibition of gastric acid secretion is related to the dose and duration of therapy.
Omeprazole is rapidly but variably absorbed after oral doses. Absorption is not significantly affected by food. Omeprazole is acid-labile and the pharmacokinetics of the various formulation develop to improve oral bioavailability may vary. The absorption of Omeprazole also appears to be dose-dependent; increasing the dosage above 40mg has been reported to increase the plasma concentrations in non-linear fashion because of saturable first-pass hepatic metabolism. In addition, bioavailability is higher after long-term use. Bioavailability of Omeprazole may be increased in elderly patients, in some ethnic groups such as Chinese, and in patients with hepatic impairment, but is not markedly affected in patients with renal impairment. On absorption, Omeprazole is almost completely metabolized in the liver, primarily by the cytochrome P450 isoenzyme CYP2C19 to form hydroxyl-omeprazole, and to a small extent by CYP3A4 to form omeprazole sulfone. The metabolites are inactive, and are excreted mostly in the urine and to a lesser extent in bile. The elimination half-life from plasma is reported to be about 0.5 to 3 hours. Omeprazole is about 95% bound to plasma proteins.
For treatment of benign gastric and duodenal ulcers including NSAID gastric and duodenal ulcers or gastroduodenal erosions, gastroesophageal reflux disease (GERD), acid related dyspepsia or disorders associated with hyper secretion of gastric acid, such as the ZollingerEllison Syndrome. It is also use in combination with antibiotics for eradication of Helicobacter pylori in peptic ulcer disease as triple therapy.
DOSAGE AND ADMINISTRATION:
For the relief of Acid-related Dyspepsia
Omeprazole is given in usual doses of 10 or 20 mg daily orally for 2 to 4 weeks.
Gastroesophageal Reflux Disease (GERD)
The usual dose is 20 mg orally once daily for 4 weeks, followed by a further 4 to 8 weeks if not fully healed.
A dose of 40mg daily may be used. Maintenance therapy after healing of esophagitis is 20 mg once daily, and for acid reflux is 10 mg daily.
Peptic Ulcer Disease
A single dose of 20mg daily, or 40 mg in severe cased, is give. Treatment is continued for 4 weeks for duodenal ulcer and 8 weeks for gastric ulcer.
For eradication of Helicobacter pylori in Peptic Ulceration
Omeprazole may be combined with antibacterials in dual or triple therapy. Effective triple therapy regimens include Omeprazole 20mg twice daily or 40mg once daily combined with: Amoxicillin 500mg and Metronidazole 500mg, both three times daily; Clarithromycin 250mg and Metronidazole 500mg (or Tinidazole 500mg) both twice daily; or with Amoxicillin 1 g and Clarithromycin 500mg, both twice daily. These regimens are given 1 week. Dual therapy regimens such as Omeprazole 20mg twice daily or 40mg daily with either Amoxicillin 750mg to 1 gram twice daily or Clarithromycin 500mg three times daily, are less effective and must be given for 2 weeks. Omeprazole alone may be continued for a further 4 to 8 weeks.
Treatment of NSAID-associated Ulceration
Doses of 20mg dialy orally are used; a dose of 20mg daily may also be used for prophylaxis in patients with a history of gastroduodenal lesions who require continued NSAID treatment.
The initial recommended dosage is 60mg orally once daily, adjusted as required. The majority of patients are effectively controlled by doses in range 20 to 120mg, but doses up to 120mg three times daily have been used. Daily doses above 80mg should be given as divided doses (usually 2).
Prophylaxis of acid aspiration during general anesthesia
Omeprazole is also used for the prophylaxis of acid aspiration during general anesthesia, in a dose of 40mg the evening before surgery and a further 40mg two to six hours before the procedure.
Dosage for Children
For the treatment of gastroesophageal reflux disease in children 1 year of age and over are determined by body-weight as follows: 10 to 20kg: 10 mg once daily; over 20mg once daily. These doses may be doubled if necessary. Treatment may be given for 4 to 12 weeks.
Omeprazole should be taken immediately before a meal, preferably in the morning. If you forget to take a dose of Omeprazole, take it as soon as you remember. If it is almost time for your next dose, skip the one you forgot and continue with your regular schedule. Do not take a double dose.
Omeprazole should not be used to patients who are/have:
- Chronic, current or history of hepatic disease;
- Presence of gastric malignancy;
- Pregnancy and lactation;
- Sensitive to Omeprazole or any component of the capsules;
- Children: Safety and efficacy for children are not established.
ADVERSE DRUG REACTIONS:
Omeprazole has a very favorable tolerability profile. Generally, Omeprazole causes few side effects such as:
Headache, diarrhea, abdominal pain, nausea, sore throat, upper respiratory infections, fever, vomiting, dizziness, rash, constipation, muscle pain, unusual tiredness, cough, and back pain.
Abdominal swelling, a feeling of ill health, angina pain, appetite loss, stool discoloration, irritable bowel, fungal infection in the esophagus, dry mouth, low blood sugar, weight gain, muscle cramps, joint and leg pains, dizziness, fainting, nervousness, sleeplessness, apathy, anxiety, unusual dreams, tingling in the hands or feet, nosebleeds, itching and inflammation of the skin, dry skin, hair loss, sweating, frequent urination, and testicle pain.
- Omeprazole and other proton pump inhibitors are metabolized by cytochrome P450 system, primarily by isoenzyme CYP2C19, and to a smaller extent by CYP3A4. Inhibitors or inducers of these isoenzymes may affect exposure to Omeprazole and other proton pump inhibitors. In turn, proton pump inhibitors may alter the metabolism of some drugs metabolized by these enzymes.
- Omeprazole may prolong the elimination of diazepam, phenytoin, and warfarin by slowing the breakdown of these drugs by liver. It may also interact with other drugs broken down by the liver.
- Omeprazole and other proton pump inhibitors can reduce the absorption of drugs such as dasatinib, ketoconazole, itraconazole, ampicillin and iron, whose absorption is dependent on the acid gastric pH.
- With voriconazole, the plasma concentration of both drugs may be increased.
- Omeprazole and other proton pump inhibitors should be used with atazanavir, as it substantially reduces exposure to atazanavir.
- The use of Omeprazole with drugs that reduce the production of blood cells by the bone marrow may increase their effect.
- Exclude the presence of gastric malignancy, as treatment with Omeprazole may delay diagnosis by alleviating symptoms.
PRECAUTIONS AND WARNINGS:
Pregnancy and Lactation
Animal studies with Omeprazole have shown toxic effects in developing fetuses, but no such problems have been reported in humans. However, as with most drugs, pregnant women, and those who might become pregnant, should not use Omeprazole unless its advantages clearly outweigh its possible dangers.
Because of tumorigenic potential of Omeprazole in animals at high doses, a decision should be made on whether nursing should be discontinued or the medicament withdrawn taking into account the importance of Omeprazole to the mother.
Elderly exhibit the same side effects seen in younger adults. However, older adults are likely to have age-related reduction in kidney and/or liver function, which could account or increased amounts of drug in the bloodstream. Report any unusual side effects to your doctor.
No specific antidote for Omeprazole overdosage is known. The drug is extensively protein bound and is, therefore, not readily dialyzed. Overdose symptoms are likely to be similar to Omeprazole's side effects. In the event of overdosage; treatment should be symptomatic and supportive. Call you local poison control center or hospital emergency room for additional information.
Store at temperatures not exceeding 30oC.