As an alternative to oral therapy for the following indications:

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 NSAID-associated gastric and duodenal ulcers • Prevention of NSAID-associated gastric and duodenal ulcers in patients at risk

• Treatment of reflux esophagitis

• Long-term management of patients with healed reflux esophagitis

• Treatment of symptomatic gastro-esophageal reflux disease

• Treatment of Zollinger-Ellison syndrome

Posology Alternative to oral therapy In patients where the use of oral medicinal products is inappropriate, intravenous Omesic 40 mg once daily is recommended. In patients with Zollinger-Ellison Syndrome the recommended initial dose of omeprazole given intravenously is 60 mg daily. Higher daily doses may be required and the dose should be adjusted individually. When doses exceed 60 mg daily, the dose should be divided and given twice daily. Omeprazole is to be administered in an intravenous infusion for 20-30 minutes. 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. Paediatric patients There is limited experience with omeprazole for intravenous use in children.

 

Known hypersensitivity to omeprazole or substituted benzimidazoles or to any of the excipients. Omeprazole, like other proton pump inhibitors (PPI), should not be administered with atazanavir.

In the presence of any alarm symptoms (e.g. significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis or melena) 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 stores or risk factors for reduced vitamin B12 absorption on long-term therapy. Omeprazole is a CYP2C19 inhibitor. When starting or ending treatment with omeprazole, the potential for interactions with medicinal products metabolised through CYP2C19 should be c onsidered. An interaction is observed between clopidogrel and omeprazole (see section 4.5). The clinical relevance of this interaction is uncertain. As a precaution, concomitant use of omeprazole and clopidogrel should be discouraged. Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter (see section 5.1). Severe hypomagnesaemia may happen in patients treated with proton pump inhibitors like omeprazole for at least three months, and in most cases for a year. Serious manifestations of hypomagnesaemia such as fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmia can occur but they may begin insidiously and be overlooked. In most affected patients, hypomagnesaemia improved after magnesium replacement and discontinuation of the proton pump inhibitor. For patients expected to be on prolonged treatment or who take proton pump inhibitors with digoxin or medicinal products that may cause hypomagnesaemia (e.g., diuretics), health care professionals should consider measuring magnesium levels before starting proton pump inhibitor 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 of this 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. Subacute cutaneous lupus erythematosus (SCLE) Proton pump inhibitors are associated with very infrequent cases of SCLE. If lesions occur, especially in sun-exposed areas of the skin, and if accompanied by arthralgia, the patient should seek medical help promptly and the health care professional should consider stopping omeprazole for intravenous. SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors. Interference with laboratory tests Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, omeprazole for intravenous treatment should be stopped for at least 5 days before CgA measurements (see section 5.1). If CgA and gastrin levels have not returned to reference range after initial measurement, measurements should be repeated 14 days after cessation of proton pump inhibitor treatment. As in all long-term treatments, especially when exceeding a treatment period of 1 year, patients should be kept under regular surveillance

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 . Co-administration of omeprazole (40 mg once daily) reduced mean nelfinavir 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

 

Concomitant administration of omeprazole (40 mg once daily) and atazanavir 300 mg/ritonavir 100 mg to may decrease 75% 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 may 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 then be reinforced. Clopidogrel clopidogrel (300 mg loading dose followed by 75 mg/day) alone and with omeprazole (80 mg at the same time as clopidogrel) are administered for 5 days. The exposure to the active metabolite of clopidogrel is decrease by 46% (Day 1) and 42% (Day 5) when clopidogrel and omeprazole are administer together. Mean inhibition of platelet aggregation (IPA) is diminish by 47% (24 hours) and 30% (Day 5) when clopidogrel and omeprazole were administered together. If administering clopidogrel and omeprazole at different times did not prevent their interaction that is likely to be driven by the inhibitory effect of omeprazole on CYP2C19. Inconsistent data on the clinical implications of this PK/PD interaction in terms of major cardiovascular events have been reported from observational and clinical studies. Other active substances The absorption of posaconazole, erlotinib, ketoconazol and itraconazol is significantly reduced and thus clinical efficacy may be impaired. For posaconazol and erlotinib concomitant use should be avoided. Active substances metabolised by CYP2C19 Omeprazole is a moderate inhibitor of CYP2C19, the major omeprazole metabolising enzyme. Thus, the metabolism of concomitant active substances also metabolised by CYP2C19, may be decreased and the systemic exposure to these substances increased. Examples of such medicinal products are R-warfarin and other vitamin K antagonists, cilostazol, diazepam and phenytoin. Cilostazol Omeprazole, given in doses of 40 mg may increase 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. 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 welltolerated 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 CYP2C19 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.

Use in pregnancy: no evidence of adverse events of omeprazole on pregnancy or on the health of the fetus/newborn child. Omisec can be used during pregnancy. Use in lactation: Omeprazole is excreted in breast milk but is not likely to influence the child when therapeutic doses are used

Omeprazole is not likely to affect the ability to drive or use machines. Adverse reactions such as dizziness and visual disturbances may occur , If affected, patients should not drive or operate machinery

Omeprazole is well tolerated and adverse reactions have generally been mild and reversible. The following have been reported as adverse events reported from routine use, but in many cases a relationship to treatment with omeprazole has not been established. The following definitions of frequencies are used: Common > 1/100; Uncommon > 1/1000 and < 1/100; Rare < 1/1000.

 

it has been reported that intravenous administration of omeprazole in doses up to 270 mg on a single day and up to 650 mg over a three-day period has not resulted in any dose-related adverse reactions.

Pharmacotherapeutic group: Drugs for acid related disorders, Proton pump inhibitors, ATC code: A02B C01 Mechanism of action Omeprazole, a racemic mixture of two enantiomers reduces gastric acid secretion through a highly targeted mechanism of action. It is a specific inhibitor of the acid pump in the parietal cell. It is rapidly acting and provides control through reversible inhibition of gastric acid secretion with once-daily dosing. Omeprazole is a weak base and is concentrated and converted to the active form in the highly acidic environment of the intracellular canaliculi within the parietal cell, where it inhibits the enzyme H+, K+- ATPase - the acid pump. This effect on the final step of the gastric acid formation process is dosedependent and provides for highly effective inhibition of both basal acid secretion and stimulated acid secretion, irrespective of stimulus. Pharmacodynamic effects All pharmacodynamic effects observed can be explained by the effect of omeprazole on acid secretion. Effect on gastric acid secretion Intravenous omeprazole produces a dose dependent inhibition of gastric acid secretion in humans. In order to immediately achieve a similar reduction of intragastric acidity as after repeated dosing with 20 mg orally, a first dose of 40 mg intravenously is recommended. This results in an immediate decrease in

intragastric acidity and a mean decrease over 24 hours of approximately 90% for both IV injection and IV infusion. The inhibition of acid secretion is related to the area under the plasma concentration-time curve (AUC) of omeprazole and not to the actual plasma concentration at a given time. No tachyphylaxis has been observed during treatment with omeprazole. Effect on H. pylori H. pylori is associated with peptic ulcer disease, including duodenal and gastric ulcer disease. H. pylori is a major factor in the development of gastritis. H. pylori together with gastric acid are major factors in the development of peptic ulcer disease. H. pylori is a major factor in the development of atrophic gastritis which is associated with an increased risk of developing gastric cancer. Eradication of H. pylori with omeprazole and antimicrobials is associated with high rates of healing and long-term remission of peptic ulcers. Other effects related to acid inhibition During long-term treatment gastric glandular cysts have been reported in a somewhat increased frequency. These changes are a physiological consequence of pronounced inhibition of acid secretion, are benign and appear to be reversible. Decreased gastric acidity due to any means including proton pump inhibitors, increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with acid-reducing medicinal products may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter. During treatment with antisecretory medicinal products, serum gastrin increases in response to the decreased acid secretion. Also CgA increases due to decreased gastric acidity. The increased CgA level may interfere with investigations for neuroendocrine tumours. Available published evidence suggests that proton pump inhibitors should be discontinued between 5 days and 2 weeks prior to CgA measurements. This is to allow CgA levels that might be spuriously elevated following PPI treatment to return to reference range.

Distribution The apparent volume of distribution in healthy subjects is approximately 0.3 l/kg body weight. Omeprazole is 97% plasma protein bound. Metabolism: Omeprazole is completely metabolised by the cytochrome P450 system (CYP). The major part of its metabolism is dependent on the polymorphically expressed CYP2C19, responsible for the formation of hydroxyomeprazole, the major metabolite in plasma. The remaining part is dependent on another specific isoform, CYP3A4, responsible for the formation of omeprazole sulphone. As a consequence of high affinity of omeprazole to CYP2C19, there is a potential for competitive inhibition and metabolic drugdrug interactions with other substrates for CYP2C19. However, due to low affinity to CYP3A4, omeprazole has no potential to inhibit the metabolism of other CYP3A4 substrates. In addition, omeprazole lacks an inhibitory effect on the main CYP enzymes. Approximately 3% of the Caucasian population and 15–20% of Asian populations lack a functional CYP2C19 enzyme and are called poor metabolisers. In such individuals the metabolism of omeprazole is probably mainly catalysed by CYP3A4. After repeated once-daily administration of 20 mg omeprazole, the mean AUC was 5 to 10 times higher in poor metabolisers than in subjects having a functional CYP2C19 enzyme (extensive metabolisers). Mean peak plasma concentrations were also higher, by 3 to 5 times. These findings have no implications for the posology of omeprazole.

Excretion Total plasma clearance is about 30-40 l/h after a single dose. The plasma elimination half-life of omeprazole is usually shorter than one hour both after single and repeated once-daily dosing. Omeprazole is completely eliminated from plasma between doses with no tendency for accumulation during oncedaily administration. Almost 80% of a dose of omeprazole is excreted as metabolites in the urine, the remainder in the faeces, primarily originating from bile secretion. Linearity/non-linearity The AUC of omeprazole increases with repeated administration. This increase is dose-dependent and results in a non-linear dose-AUC relationship after repeated administration. This time- and dosedependency is due to a decrease of first pass metabolism and systemic clearance probably caused by an inhibition of the CYP2C19 enzyme by omeprazole and/or its metabolites (e.g. the sulphone). No metabolite has been found to have any effect on gastric acid secretion. Special populations Impaired hepatic function The metabolism of omeprazole in patients with liver dysfunction is impaired, resulting in an increased AUC. Omeprazole has not shown any tendency to accumulate with once-daily dosing. Impaired renal function The pharmacokinetics of omeprazole, including systemic bioavailability and elimination rate, are unchanged in patients with reduced renal function . Elderly The metabolism rate of omeprazole is somewhat reduced in elderly subjects (75-79 years of age).

Gastric ECL-cell hyperplasia and carcinoids have been observed in life-long studies in rats treated with omeprazole. These changes are the result of sustained hypergastrinaemia secondary to acid inhibition. Similar findings have been made after treatment with H2-receptor antagonists, proton pump inhibitors and after partial fundectomy. Thus, these changes are not from a direct effect of any individual active substance

Sodium Hydroxide, Edetate Disodium and Water for Injection

Omeprazole powder for solution for infusion should not be mixed with other medicinal products than those mentioned in section 6.6

2 years Reconstituted solution: Chemical and physical in-use stability has been demonstrated for 12 hours when dissolved in NaCl 0.9% solution and for 6 hours in 5% glucose when reconstituted under controlled aseptic conditions and stored at 30 °C . Chemical and physical in-use stability has also been demonstrated for 24 hours at 2-8°C in both NaCl 0.9% solution and 5% glucose. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8 °C, unless reconstitution has taken place in controlled and aseptic conditions.

Do not store above 30°C & protect from light

Clear Tubular Glass Vial 6R with Rubber Stopper 20mm Lyo.

The entire contents of each vial is to be dissolved in approximately 5 ml and then immediately diluted to 100 ml. Sodium chloride 9 mg/ml (0.9%) solution for infusion or glucose 50 mg/ml (5%) solution for infusion must be used. The stability of omeprazole is influenced by the pH of the solution for infusion, which is why no other solvent or quantities should be used for dilution. Preparation 1. With a syringe draw 5 ml of infusion solution from the 100 ml infusion bottle or bag. 2. Add this volume to the vial with the freeze-dried omeprazole, mix thoroughly making sure all omeprazole is dissolved. 3. Draw the omeprazole solution back into the syringe. 4. Transfer the solution into the infusion bag or bottle. 5. Repeat steps 1-4 to make sure all omeprazole is transferred from the vial into the infusion bag or bottle. Alternative preparation for infusions in flexible containers 1. Use a double-ended transfer needle and attach to the injection membrane of the infusion bag. Connect the other needle-end from the vial with freeze-dried omeprazole. 2. Dissolve the omeprazole substance by pumping the infusion solution back and forward between the infusion bag and the vial. 3. Make sure all omeprazole is dissolved. The solution for infusion is to be administered in an intravenous infusion for 20-30 minutes. After reconstitution the solution is colorless, clear, practically free from visible particles. Any unused product or waste material should be disposed of in accordance with local requirements.