Omeprazole

FORMULATION
Each delayed-release capsule contains:
Omeprazole…………….. 20 mg

DESCRIPTION
Omeprazole belongs to a class of antisecretory compounds, substituted Benzimidazoles, that do not exhibit anticholinergic or H2 histamine antagonistic properties, but that suprress gastric acid secretion by specific inhibition of the HIK ATP ase enzyme system at the secretory surface of the gastric parietal cell. Because this enzyme is the “acid (proton) pump” within the gastric mucosa, omeprazole has been characterized as a gastric acid pump inhibitor: It blocks the final step of acid production. The effect is dose related and inhibit both basal and stimulated acid secretion regardless of the stimulus.

MECHANISM OF ACTION
Suppresses gastric acid scretion by inhibiting the parietal cell H+/K ATP* pump.

PHARMACOKINETICS
Onset of anti-secretory action: Oral: Within 1 hour.
Peak effect: 72 hours
Protein binding: 95%
Metabolism: Extensive in the liver
Halflife: 0.5 -1 hour

INDICATIONS
Omeprazole capsules are indicated for:
Adults

• Treatment of duodenal ulcers
• Prevention of relapse of duodenal ulcers
• Treatment of gastric ulcers
• Prevention of relapse of gastric ulcers
• In combination with appropriate antibiotics, Helicobacter pylori (H. pylori) eradication in peptic ulcer disease

• Treatment of NSA ID-associated gastric and duodenal ulcers
• Prevention of NSAlD-associated gastric and duodenal ulcers in patients at risk

• Treatment of reflux oesophagitis
• Long-term management of patients with healed reflux esophagitis
• Treatment of symptomatic gastro-esophageal reflux disease
• Treatment of Zollinger-Ellison syndrome

Paediatric use Children over 1 yearofage and > 10 kg

• Treatment of reflux esophagitis
• Symptomatic treatment of heartburn and acid regurgitation in gastro-oesophageal reflux disease Children and adolescents over 4 years ofage

• In combination with antibiotics in treatment of duodenal ulcer causedby H. pylori

CONTRAINDICATION
Known hypersensitivity to omeprazole. Omeprazole like other proton pump inhibitors (PPIs) schould not be used concomitantly with nelfinavir.

ADVERSE EFFECTS
The adverse effects reported most frequently with omeprazole capsules have been diarrhoea, skin rashes, and headache; they have been sometimes been severe enough to require discontinuation of treatment. Effects on the central nervous system, including reversible states in severely ill patients, have occurred. Other adverse effects reported rarely include anthralgia and myalgia, blood disorders including leucopoenia and thrombocytopenia, interstitial nephritis and hepatotoxicity.

DOSAGE AND ADMINISTRATION
Adults: Oral: GERD or erosive esophagitis: 20 mg/day for 4-8 weeks. Phatologically hypersecretory—conditions: 60 mg once daily to start; doses up to 120 mg 3 been administered; administered daily doses >80 mg in divided doses. Helicobacter pylori: combination therapy with bismuth subsalicylate, tetracycline, and clarithromycin; or with clarithromycin alone.

Adult dose: Oral: 20mg twice daily
Gastric ulcers: 40mg/day for 8-8 weeks.

Dosage
Alternative to oral therapy In patients where the use of oral medicinal products is inappropriate, Losec IV 40 mg once daily is recommended. In patients with Zollinger- Ellison syndrome the recommended initial dose of Losec given intravenously is 60 mg daily. Higher doses may be required and the dose should be adjusted individually. When the dose exceeds 60 mg daily, the dose should be divided and given twice daily. Omeprazole for injection must be given only as an intravenous injection and it must be added to infusion solution. After reconstitution the injection should be given slowly over a period of at least 2.5 minutes at a maximum rate of 4 mL per minute. For instructions on reconstitution of the product before administration.

Special Populations
Impaired renal function
Dose adjustment is not needed in patients with impaired renal function.

Impaired hepatic function
In patients with impaired hepatic function a daily dose of 10-20 mg may be sufficient.

Elderly (> 65 years old)
Dose adjustment is not needed in the elderly.

Pediatric patients
There is limited experience with Omeprazole for intravenous use in children

WARNING AND PRECAUTIONS
In long-term (2-year) studies in rats, omeprazole produced a dose- related increase in gastrin carcinoid tumors. While available endoscopic evaluations and histologic examinations of biopsy specimen form human stomach have not detected a risk form short- term exposure to omeprazole, further human data on the effect of sustained hypochlorhydria and hypergastrinemia are needed to rule out the possibility of an increased risk for the development of tumors in humans receiving long-term therapy. Bioavailability may be increased in elderly. In the presence of any alarm symptoms (e.g. significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis or melaena) and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment may alleviate symptoms and delay diagnosis. Co-administration of atazanavir with proton pump inhibitors is not recommended. If the combination of atazanavir with a proton pump inhibitor is judged unavoidable, close clinical monitoring (e.g. virus load) is recommended in combination with an increase in the dose of atazanavir to 400 mg with 100 mg of ritonavir; omeprazole 20 mg should not be exceeded. Omeprazole, as all acid-blocking medicinal products, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be considered in patients with reduced body fat stores or risk factors for reduced vitamin B12 absorption on long- term therapy. Omeprazole is a CYP2C19 enzyme inhibitor. When starting or ending treatment with omeprazole, the potential for interactions with drugs metabolised via CYP2C19 should be considered. An interaction is observed between clopidogrel and omeprazole. The clinical relevance of this interaction is uncertain. As a precaution, concomitant use of omeprazole and clopidogrel should be discouraged. Severe hypomagnesemia has been reported in patients treated with proton pump inhibitors PPIs) like omeprazole for at least three months, and in most case for a year. Serious manifestations of hypomagnesemia such as fatigue, ‘tetanyjdeljrium dizziness and ventricular arrhythmia can occur btw they may begin. insidiously and be overlooked. In most affected patients, hypomagnesemia improved after magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPIs with digoxin or drugs that may cause hypomagnesaemia (e.g diuretics), healthcare professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment. Proton pump inhibitors, especially if used in high doses and over long durations (>1 year), may modestly increase the risk of hip, wrist and spine fracture, predominantly in the elderly or in presence of other recognised risk factors. Observational studies suggest that proton pump inhibitors may increase the overall risk of fracture by 10-40%. Some ofthis increase may be due to other risk factors. Patients at risk of osteoporosis should receive care according to current clinical guidelines and they should have an adequate intake of vitamin D and calcium.

Interference with laboratory tests
Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, omeprazole treatment should be stopped for at least 5 days before CgA measurements. Some children with chronic illnesses may require long-term treatment although it is not recommended. Omeprazole contains lactose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase- isomaltase insufficiency should not take this medicine. Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter. As in all long-term treatments, especially when exceeding a treatment period of 1 year, patients should be kept under regular surveillance.

DRUG INTERACTIONS
Effects of omeprazole on the pharmacokinetics of other active substances Active substances with pH dependent absorption. The decreased intragastric acidity during treatment with omeprazole might increase or decrease the absorption of active substances with a gastric pH dependent absorption. Nelfinavir, atazanavir The plasma levels of nelfinavir and atazanavir are decreased in case of co-administration with omeprazole. Concomitant administration of omeprazole with nelfinavir is contraindicated (see section 4.3). Co-administration of omeprazole (40 mg once daily) reduced mean nelvinavir exposure by ca. 40% and the mean exposure of the pharmacologically active metabolite M8 was reduced by ca. 75-90%. The interaction may also involve CYP2C19 inhibition. Concomitant administration of omeprazole with atazanavir is not recommended (see section 4.4). Concomitant administration of omeprazole (40 mg once daily) and atazanavir 300 mg/ritonavir 100 mg to healthy volunteers resulted in a 75% decrease of the atazanavir exposure. Increasing the atazanavir dose to 400 mg did not compensate for the impact of omeprazole on atazanavir exposure. The co-administration of omeprazole (20 mg once daily) with atazanavir 400 mg/ritonavir 100 mg to healthy volunteers resulted in a decrease of approximately 30% in the atazanavir exposure as compared to
atazanavir 300 mg/ritonavir 100 mg once daily.

Digoxin
Concomitant treatment with omeprazole (20 mg daily) and digoxin in healthy subjects increased the bioavailability of digoxin by 10% Digoxin toxicity has been rarely reported. However, caution should be exercised when omeprazole is given at high doses in elderly patients. Therapeutic drug monitoring of digoxin should be then be reinforced.

Clopidogrel
Results from studies in healthy subjects have shown a pharmacokinetic (PK)/pharmacodynamic (PD) interaction between clopidogrel (300 mg loading dose/75 mg daily maintenance dose) and omeprazole (80 mg p.o. daily) resulting in a decreased exposure to the active metabolite of clopidogrel by an average of 46% and a decreased maximum inhibition of (ADP induced) platelet aggregation by an average of 16%. Inconsistent data on the clinical implications of a PK/PD interaction of omeprazole in terms of major cardiovascular events have been reported from both observational and clinical studies. As a precaution, concomitant use of omeprazole and clopidogrel should be discouraged. Other active substances The absorption of posaconazole, erlotinib, ketoconazole and itraconazole is significantly reduced and thus clinical efficacy may be impaired. For posaconazole and erlotinib concomitant use should be avoided Active substances metabolised by CYP2C19 Omeprazole is a moderate inhibitor of CYP2C19, the major omeprazole metabolising enzyme. Thusy the me!qbolism of concomitant active substances also metabolised by CYP2C19, may be decreased and the systemic exposure to these substances increased. Examples of such drugs are R-warfarin and other vitamin K antagonists, cilostazol, diazepam and phenytoin Cilostazol Omeprazole, given in doses of 40 mg to healthy subjects in a cross-over study, increased Cmax and AUC for cilostazol by 18% and 26% respectively, and one of its active metabolites by 29% and 69% respectively.

Phenytoin
Monitoring phenytoin plasma concentration is recommended during the first two weeks after initiating omeprazole treatment and, if a phenytoin dose adjustment is made, monitoring and a further dose adjustment should occur upon ending omeprazole treatment.

Unknown mechanism
Saquinavir
Concomitant administration of omeprazole with saquinavir/ritonavir resulted in increased plasma levels up to approximately 70% for saquinavir associated with good tolerability in HIV-infected patients.

Tacrolimus
Concomitant administration of omeprazole has been reported to increase the serum levels of tacrolimus. A reinforced monitoring of tacrolimus concentrations as well as renal function (creatinine clearance) should be performed, and dosage of tacrolimus adjusted if needed.

Methotrexate
When given together with proton pump inhibitors, methotrexate levels have been reported to increase in some patients. In high-dose methotrexate administration a temporary withdrawal of omeprazole may need to be considered. Effects of other active substances on the pharmacokinetics of omeprazole. Inhibitors of CYP2C19 and/or CYP3A4 Since omeprazole is metabolised by CYP2C19 and CYP3A4, active substances known to inhibit CYP2C19 or CYP3A4 (such as clarithromycin and voriconazole) may lead to increased omeprazole serum levels by decreasing omeprazole’s rate of metabolism Concomitant voriconazole treatment resulted in more than doubling of the omeprazole exposure. As high doses of omeprazole have been well-tolerated adjustment of the omeprazole dose is not generally required. However, dose adjustment should be considered in patients with severe hepatic impairment and if long-term treatment is indicated. Inducers of CYP2C19 and/or CYP3A4 Active substances known to induce CYP2CI 9 or CYP3A4 or both (such as rifampicin and St John’s wort) may lead to decreased omeprazole serum levels by increasing omeprazole’s rate of metabolism.

CAUTION
Foods, Drugs, Devices, and Cosmetics Act prohibits dispensing without prescription.

STORAGE CONDITION
Store at temperatures not exceeding 300C. Protect from light.

Keep all medicines out of reach of children.

Price/SRP per piece:

• SRP 12.50 per capsule

“For suspected adverse drug reaction, report to the FDA: www.fda.gov.ph”.