Omeprazole

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT OMEPRAZOLE (OMEPRAZOLE)

Composition:

Active substance: omeprazole;

1 hard enteric-coated capsule contains omeprazole 20.0 mg;

Excipients: spherical sugar (1), magnesium hydroxide (2), anhydrous sodium hydrogen phosphate, hypromellose type 2910, sodium lauryl sulfate, mannitol (E421), sodium starch glycolate (type A), talc, titanium dioxide (E171), macrogol 6000, polysorbate 80, methacrylate copolymer dispersion (3);

Capsule shell: indigotine-FD&C Blue 2 (E132), titanium dioxide (E171), gelatin.

(1) Spherical sugar: sucrose (sucrose), corn starch, purified water.

(2) Magnesium hydroxide 90% + corn starch 10%.

(3) Dry substance.

Pharmaceutical form. Hard enteric-coated capsules.

Main physicochemical properties: hard gelatin capsules of size "4", with a blue cap and a white body, containing spherical pellets of white, almost white, or white-cream color.

Pharmacotherapeutic group.

Drugs for treatment of peptic ulcer and gastroesophageal reflux disease. Proton pump inhibitors. ATC code A02BC01.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action.

Omeprazole, a racemic mixture of two enantiomers, reduces gastric acid secretion through a targeted mechanism of action. It is a specific inhibitor of the gastric proton pump in parietal cells. It acts rapidly and provides sustained suppression of gastric acid secretion when administered once daily.

Omeprazole is a weak base that accumulates and is converted into its active form in the acidic environment of the intracellular canaliculi of parietal cells, where it inhibits the enzyme H+K+-ATPase—the proton pump. This effect on the final stage of gastric acid production is dose-dependent and results in highly effective suppression of both basal and stimulated acid secretion, regardless of the nature of the stimulus.

All observed pharmacodynamic effects are based on omeprazole's effect on acid secretion.

Effect on gastric acid secretion

Oral administration of omeprazole once daily provides rapid and effective inhibition of gastric acid secretion during both daytime and nighttime, with maximum effect achieved within 4 days of treatment.

Administration of omeprazole 20 mg to patients with duodenal ulcer results in a mean reduction of intragastric acidity of at least 80% over 24 hours, which is maintained over time, and a mean reduction of peak acid output after pentagastrin stimulation of approximately 70% 24 hours after drug intake.

Oral administration of omeprazole 20 mg to patients with duodenal ulcer maintains intragastric pH ≥ 3 for an average of 17 out of 24 hours after dosing.

Due to reduced acid secretion and intragastric acidity, omeprazole dose-dependently reduces/normalizes acid exposure in the esophagus in patients with gastroesophageal reflux disease (GERD). Acid secretion suppression correlates with the area under the pharmacokinetic curve (AUC) of omeprazole, rather than with the plasma concentration at any given time point.

No cases of tachyphylaxis have been observed during omeprazole treatment.

Effect on Helicobacter pylori (H. pylori)

H. pylori is associated with peptic ulcer disease of the stomach and duodenum. H. pylori is a major factor in the development of gastritis, including atrophic gastritis, which is associated with an increased risk of gastric cancer.

Eradication of H. pylori with omeprazole and antibiotics provides a high cure rate and long-term remission of peptic ulcers.

Various dual therapy regimens have been analyzed and found to be less effective than triple therapy. However, dual therapy may be considered in cases where high susceptibility excludes the use of any triple combination.

Other effects related to acid suppression

During long-term treatment, a higher incidence of gastric fundic gland polyps has been observed. These changes are a physiological consequence of profound acid secretion suppression, are benign, and appear to be reversible.

Reduction of gastric acidity by any means, including proton pump inhibitors (PPIs), increases the number of bacteria normally present in the gastrointestinal tract. Treatment with acid-reducing agents slightly increases the risk of gastrointestinal infections, particularly those caused by Salmonella, Campylobacter, and Clostridium difficile, in hospitalized patients.

During treatment with antisecretory drugs, serum gastrin levels increase in response to reduced acid secretion. Due to decreased gastric acidity, chromogranin A (CgA) levels rise. Elevated CgA levels may interfere with neuroendocrine tumor diagnostics. Data suggest that proton pump inhibitor (PPI) therapy should be discontinued 5–14 days before CgA measurements to allow CgA levels, which may be elevated due to PPI treatment, to return to the reference range.

During long-term omeprazole treatment, an increase in the number of enterochromaffin-like (ECL) cells has been observed in some patients (both children and adults), possibly related to elevated serum gastrin levels. These findings are considered to have no clinical significance.

Children

In an uncontrolled study in children (aged 1 to 16 years) with severe reflux esophagitis, omeprazole at doses of 0.7 to 1.4 mg/kg improved esophagitis in 90% of cases and significantly reduced reflux symptoms. In a simple blind study, children aged 0 to 24 months with a clinically confirmed diagnosis of gastroesophageal reflux disease received omeprazole at doses of 0.5, 1.0, or 1.5 mg/kg body weight. The frequency of vomiting/regurgitation episodes decreased by 50% after 8 weeks of treatment, regardless of dose.

H. pylori eradication in children

A randomized, double-blind clinical trial (the Héliot study) concluded that omeprazole in combination with two antibiotics (amoxicillin and clarithromycin) is safe and effective in treating H. pylori infection in children aged 4 years and older with gastritis. H. pylori eradication rates were 74.2% (23/31 patients) with omeprazole + amoxicillin + clarithromycin compared to 9.4% (3/32 patients) with amoxicillin + clarithromycin alone. However, no clinical benefit regarding dyspeptic symptoms was demonstrated. Data in children under 4 years of age are lacking.

Pharmacokinetics.

Absorption

Omeprazole and omeprazole magnesium are acid-labile and therefore administered orally as enteric-coated granules in capsules or tablets. Omeprazole absorption is rapid, with peak plasma levels reached approximately 1–2 hours after dosing. Absorption of omeprazole occurs in the small intestine and is usually complete within 3–6 hours. Concomitant food intake does not affect bioavailability. Systemic availability (bioavailability) of a single dose of omeprazole is approximately 40%. After repeated once-daily dosing, bioavailability increases to approximately 60%.

Distribution

The volume of distribution in healthy volunteers is 0.3 L/kg body weight. Omeprazole is approximately 97% bound to plasma proteins.

Biotransformation.

Omeprazole is completely metabolized by the cytochrome P450 (CYP) system. The majority of metabolism depends on the polymorphically expressed CYP2C19, responsible for the formation of hydroxyomeprazole, the main metabolite in plasma. The remainder depends on another specific isoenzyme, CYP3A4, responsible for the formation of omeprazole sulfone. Due to omeprazole's high affinity for CYP2C19, there is potential for competitive inhibition and metabolic interaction with other CYP2C19 substrates. However, due to its low affinity for CYP3A4, omeprazole does not inhibit the metabolism of other CYP3A4 substrates. Additionally, omeprazole does not inhibit major CYP enzymes.

Approximately 3% of the Caucasian population and 15–20% of Asian populations lack functional CYP2C19 enzyme and are referred to as poor metabolizers. In these individuals, omeprazole metabolism is likely primarily catalyzed by CYP3A4. After repeated once-daily administration of 20 mg omeprazole, the mean AUC was 5–10 times higher in poor metabolizers than in individuals with functional CYP2C19 (extensive metabolizers). Mean peak plasma concentrations were also 3–5 times higher. These observations have no implications for omeprazole dosing.

Elimination.

The terminal half-life of omeprazole in plasma is typically less than 1 hour, both after single and multiple oral doses once daily. Omeprazole is completely eliminated from plasma between doses, with no tendency for accumulation during once-daily administration. Approximately 80% of an oral dose of omeprazole is excreted in urine as metabolites, and the remainder in feces, primarily via biliary secretion.

Linearity/Non-linearity.

With repeated administration, the AUC of omeprazole increases. This dose-dependent increase results in a non-linear relationship between dose and AUC after repeated dosing. This time- and dose-dependent relationship is attributed to reduced presystemic metabolism and systemic clearance, possibly due to inhibition of the CYP2C19 enzyme by omeprazole and/or its metabolites (e.g., sulfone).

No effect of the metabolite on gastric acid secretion has been demonstrated.

Patients with hepatic impairment. Omeprazole metabolism is impaired in patients with liver dysfunction, leading to increased AUC. However, with once-daily dosing, no tendency for omeprazole accumulation was observed.

Patients with renal impairment. The pharmacokinetics of omeprazole, including systemic bioavailability and elimination rate, remain unchanged in patients with renal impairment.

Elderly patients. The rate of metabolism in elderly patients (75–79 years) is slightly reduced.

Children. During treatment of children aged 1 year and older using recommended doses, plasma concentrations similar to those in adult patients were observed. In children under 6 months of age, omeprazole clearance is reduced due to low metabolic capacity.

Clinical characteristics.

Indications

Adults

• For the treatment of duodenal ulcer;
• for prevention of recurrence of duodenal ulcer;
• for the treatment of benign gastric ulcer;
• for prevention of recurrence of benign gastric ulcer;
• for eradication of H. pylori in patients with peptic ulcer (as part of combination therapy with antibacterial agents);
• for the treatment of gastric and duodenal ulcers associated with use of nonsteroidal anti-inflammatory drugs (NSAIDs);
• for prevention of gastric and duodenal ulcers associated with NSAID use in high-risk patients;
• for the treatment of reflux esophagitis;
• for long-term management of patients with gastroesophageal reflux disease (GERD);
• for treatment of GERD symptoms;
• for the treatment of Zollinger–Ellison syndrome.

Children

Children aged 1 year and older with body weight above 10 kg:

• for the treatment of reflux esophagitis;
• for symptomatic treatment of heartburn and acid regurgitation in GERD;

Children aged 4 years and older:

• for the treatment of H. pylori-associated duodenal ulcer in combination with antibiotics (see section "Dosage and administration").

Contraindications

Hypersensitivity to omeprazole, substituted benzimidazoles, or to any of the excipients of the medicinal product.

Omeprazole, like other PPIs, should not be used concomitantly with nelfinavir (see section "Interaction with other medicinal products and other types of interactions").

Interaction with other medicinal products and other types of interactions

Effect of omeprazole on the pharmacokinetics of other medicinal products

Medicinal products whose absorption is pH-dependent

Reduced gastric acidity during omeprazole therapy may increase or decrease absorption of drugs whose absorption depends on gastric pH.

Nelfinavir and atazanavir

Plasma concentrations of nelfinavir and atazanavir are reduced when these agents are administered concomitantly with omeprazole.

Concomitant use of omeprazole and nelfinavir is contraindicated (see section "Contraindications").

Concomitant administration of omeprazole (40 mg once daily) reduces the average exposure to nelfinavir by approximately 40%, and the average exposure to its pharmacologically active metabolite M8 is reduced by approximately 75–90%. The interaction may also involve inhibition of CYP2C19.

Concomitant use of omeprazole and atazanavir is not recommended. Coadministration of omeprazole (40 mg once daily) with atazanavir 300 mg/ritonavir 100 mg combination reduced atazanavir exposure by 75% in healthy volunteers. Increasing the atazanavir dose to 400 mg does not compensate for the effect of omeprazole on atazanavir exposure. In healthy volunteers, coadministration of omeprazole (20 mg once daily) with atazanavir 400 mg/ritonavir 100 mg combination resulted in a 30% reduction in atazanavir exposure compared to administration of atazanavir 300 mg/ritonavir 100 mg once daily.

Digoxin

Concomitant treatment with omeprazole (20 mg daily) and digoxin increases digoxin bioavailability by 10%. Rare cases of digoxin-induced toxicity have been reported. However, caution should be exercised when prescribing high doses of omeprazole to elderly patients. Patients receiving digoxin concomitantly should be closely monitored by a physician.

Clopidogrel

Data on the concomitant use of clopidogrel and omeprazole are conflicting regarding reduction in the concentration of clopidogrel's active metabolite and the clinical implications of this pharmacokinetic/pharmacodynamic interaction in terms of major cardiovascular events. Concomitant use of omeprazole and clopidogrel should be avoided. When used together, the effect of clopidogrel's active metabolite was reduced by an average of 46%, and maximum inhibition of (ADP-induced) platelet aggregation was reduced by an average of 16%. In another study, administration of clopidogrel and omeprazole at different times did not prevent their interaction, likely due to omeprazole's inhibitory effect on CYP2C19. Conflicting data on the clinical manifestations of this pharmacokinetic/pharmacodynamic (PK/PD) interaction in terms of major cardiovascular diseases have been observed in observational and clinical studies. Therefore, concomitant use of omeprazole and clopidogrel should be avoided.

Ketoconazole, itraconazole, posaconazole, erlotinib. As with other agents that suppress gastric acidity, absorption, and thus clinical efficacy, of these medicinal products may be reduced during omeprazole therapy. Concomitant use of omeprazole with posaconazole and erlotinib should be avoided.

Active substances metabolized by CYP2C19

Omeprazole is a moderate inhibitor of CYP2C19, the main enzyme involved in omeprazole metabolism. Thus, when used concomitantly with active substances that are also metabolized by CYP2C19, their metabolism may be impaired and systemic exposure increased. Examples include R-warfarin and other vitamin K antagonists, cilostazol, diazepam, and phenytoin.

Cilostazol

In healthy volunteers, administration of omeprazole 40 mg increased Cmax and AUC of cilostazol by 18% and 26%, respectively, and of one of its active metabolites by 29% and 69%, respectively.

Phenytoin

Monitoring of phenytoin levels, as well as oral anticoagulants, is recommended, with dose reduction if necessary. During the first two weeks after initiation of omeprazole therapy, monitoring of plasma phenytoin concentration is recommended. After discontinuation of omeprazole, monitoring and further dose adjustment of phenytoin may be required if the dose was adjusted during omeprazole treatment.

Interactions with unknown mechanisms

Saquinavir

Coadministration of omeprazole with saquinavir/ritonavir increased saquinavir plasma concentrations by approximately 70%, which was associated with good tolerability in HIV-infected patients.

Tacrolimus

Increased serum concentrations of tacrolimus have been reported with concomitant use of omeprazole. Serum tacrolimus concentrations and renal function (creatinine clearance) should be monitored continuously during concomitant use with omeprazole, and the tacrolimus dose adjusted if necessary.

Methotrexate

There are data indicating increased methotrexate levels in some patients when administered concomitantly with PPIs. When high-dose methotrexate is required, temporary discontinuation of omeprazole should be considered.

Effect of other medicinal products on omeprazole pharmacokinetics

Inhibitors of CYP2C19 and CYP3A4

Since omeprazole is metabolized by CYP2C19 and CYP3A4, medicinal products that inhibit CYP2C19 and CYP3A4 (such as clarithromycin and voriconazole) may cause increased omeprazole serum levels by slowing its metabolism. Concomitant use of voriconazole may lead to more than a twofold increase in omeprazole exposure. Since high doses of omeprazole are well tolerated, dose adjustment is not required during short-term concomitant use. However, dose adjustment should be considered in patients with severe hepatic impairment and in cases of long-term treatment.

Inducers of CYP2C19 and CYP3A4

Medicinal products that induce CYP2C19 and CYP3A4 (such as rifampicin, St. John’s wort) may lead to decreased omeprazole serum levels by accelerating its metabolism.

Special precautions for use

If any alarming symptom occurs (e.g., marked weight loss, recurrent vomiting, dysphagia, hematemesis or melena) and if gastric ulcer is present or suspected, malignancy must be excluded, as treatment may alleviate symptoms and delay diagnosis.

Concomitant use of atazanavir with PPIs is not recommended. If co-administration of atazanavir with a PPI cannot be avoided, careful clinical monitoring (e.g., viral load) combined with increased atazanavir dose to 400 mg with 100 mg ritonavir is recommended; omeprazole dose should not exceed 20 mg.

Omeprazole, like all medicinal products that suppress gastric acid secretion, may reduce absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be considered in patients with cachexia or risk factors for reduced vitamin B12 absorption during long-term therapy.

Renal function impairment

Acute interstitial nephritis (AIN) has been observed in patients taking omeprazole and may occur at any time during omeprazole therapy (see section "Adverse reactions"). Acute interstitial nephritis may progress to renal failure.

If AIN is suspected, omeprazole should be discontinued and appropriate treatment initiated immediately.

Omeprazole is an inhibitor of CYP2C19. Potential interactions with medicinal products metabolized by CYP2C19 should be considered when starting or stopping omeprazole therapy. An interaction has been observed between clopidogrel and omeprazole. The clinical significance of this interaction is not fully established. Concomitant use of omeprazole and clopidogrel should be avoided.

In patients receiving PPIs, including omeprazole, for at least 3 months, significant hypomagnesemia may occur (in most cases, patients had been taking the drug for approximately 1 year). Hypomagnesemia may manifest as severe symptoms such as fatigue, muscle spasms, seizures, delirium, dizziness, and ventricular arrhythmias. However, it should be noted that in some cases symptoms may be masked, hindering timely recognition of this complication. In most patients, symptoms resolve and magnesium levels normalize after magnesium supplementation and discontinuation of the PPI.

In patients requiring long-term PPI therapy, and in those concomitantly taking digoxin or other medicinal products that may cause hypomagnesemia (e.g., diuretics), magnesium levels should be checked before starting treatment and periodically during therapy.

Some data suggest a causal relationship between PPI use and increased risk of osteoporosis-related fractures, especially when PPIs are used at high doses and for prolonged periods (>1 year), particularly fractures of the hip, wrist, and spine, mainly in elderly patients or those with other risk factors. Therefore, patients with progressive osteoporosis and risk of osteoporotic fractures require clinical monitoring according to current clinical guidelines and adequate intake of vitamin D and calcium.

Subacute cutaneous lupus erythematosus

The use of proton pump inhibitors has been associated with very rare cases of subacute cutaneous lupus erythematosus. If skin manifestations, particularly in sun-exposed areas, occur together with arthralgia, patients should seek immediate medical advice and discontinuation of omeprazole should be considered. A history of subacute cutaneous lupus erythematosus following PPI use may increase the risk of developing subacute cutaneous lupus erythematosus with other PPIs.

Do not use if you are allergic to omeprazole.

Omeprazole may cause serious skin reactions. Symptoms may include: redness of the skin, blisters, rash.

If an allergic reaction occurs, stop using the medicine and seek immediate medical help.

Effect on laboratory tests

During treatment with antisecretory drugs, plasma gastrin concentration increases as a result of reduced gastric acid secretion. Due to reduced gastric acid secretion, chromogranin A (CgA) levels increase. Elevated CgA levels may interfere with test results for detecting neuroendocrine tumors. To avoid such interference, PPI therapy should be discontinued at least 5 days before measuring CgA levels. If CgA and gastrin levels do not return to normal range after initial measurements, these parameters should be rechecked 14 days after discontinuation of PPI therapy.

For treatment of chronic conditions, the drug should not be used in children longer than recommended.

The product contains sucrose (in sugar spheres) as an excipient; therefore, patients with diagnosed intolerance to certain sugars should consult their physician before taking this medicine.

PPI therapy may increase the risk of gastrointestinal infections caused by Salmonella and Campylobacter, and possibly also Clostridium difficile in hospitalized patients.

As with any long-term therapy, especially if duration exceeds 1 year, the patient should remain under medical supervision.

Use during pregnancy or breastfeeding

Epidemiological data (over 1000 cases) indicate no adverse effect of omeprazole on pregnancy or on fetal/newborn health. Omeprazole may be used during pregnancy.

Omeprazole passes into breast milk, but its effect on the infant is unknown; therefore, breastfeeding should be avoided during treatment with this medicine.

Effect on ability to drive and use machines

It is unlikely that the medicinal product affects the ability to drive or operate machinery. Adverse reactions such as dizziness and visual disturbances may occur (see section "Adverse reactions"). If such disorders occur, patients should not drive or operate machinery.

Method of Administration and Dosage

Dosage for Adults

Duodenal Ulcer Treatment

In the absence of H. pylori, the recommended dose for patients with duodenal ulcer is 20 mg of omeprazole once daily. In most patients, healing of duodenal ulcer occurs within 2 weeks. For patients who have not fully healed after the initial course, further treatment for 2 weeks is recommended. For patients with poor response to therapy, the recommended dose is 40 mg of omeprazole daily; ulcer healing is usually achieved within 4 weeks.

Prevention of Recurrence of Duodenal Ulcers

For prevention of recurrence of duodenal ulcers in patients with a negative H. pylori test or when eradication of H. pylori is not feasible, the recommended dose is 20 mg of omeprazole once daily. A daily dose of 10 mg* may be sufficient for some patients. If treatment is ineffective, the dose may be increased to 40 mg.

Treatment of Benign Gastric Ulcers

In the absence of H. pylori, the recommended dose is 20 mg of omeprazole once daily. In most patients, gastric ulcer heals within 4 weeks. For patients who have not fully healed after the initial course, further treatment for 4 weeks is recommended. For patients with poor response to therapy, the recommended dose is 40 mg of omeprazole daily; gastric ulcer healing usually occurs within 8 weeks.

Prevention of Recurrence of Benign Gastric Ulcers

The recommended dose for prevention of recurrence in patients with poor response of gastric ulcer to therapy is 20 mg of omeprazole once daily. If necessary, the dose may be increased to 40 mg once daily.

H. pylori Eradication in Peptic Ulcer Disease

For H. pylori eradication, selection of antibacterial agents should consider individual tolerability, local resistance patterns, and treatment guidelines:

• omeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1000 mg twice daily for 1 week, or
• omeprazole 20 mg + clarithromycin 250 mg (if necessary, 500 mg) + metronidazole 400 mg (if necessary, 500 mg) or tinidazole 500 mg twice daily for 1 week, or
• omeprazole 40 mg once daily + amoxicillin 500 mg + metronidazole 400 mg (if necessary, 500 mg) or tinidazole 500 mg three times daily for 1 week.

In each regimen, if the patient remains H. pylori-positive, the treatment may be repeated.

Treatment of Gastric and Duodenal Ulcers Associated with NSAID Use

For treatment of gastric and duodenal ulcers associated with NSAID use, the recommended dose is 20 mg of omeprazole once daily. In most patients, ulcer healing occurs within 4 weeks. For patients who have not fully healed after the initial course, further treatment for 4 weeks is recommended.

Prevention of Gastric and Duodenal Ulcers Associated with NSAID Use in High-Risk Patients

For prevention of gastric and duodenal ulcers associated with NSAID use in high-risk patients (age over 60 years, history of gastric or duodenal ulcer, history of upper gastrointestinal bleeding), the recommended dose is 20 mg of omeprazole once daily.

Gastroesophageal Reflux Disease (GERD) with Esophagitis

The recommended dose is 20 mg of omeprazole once daily. In most patients, healing occurs within 4 weeks. For patients who have not fully healed after the initial course, further treatment for another 4 weeks is recommended. For patients with severe esophagitis, 40 mg of omeprazole daily is recommended, with healing usually achieved within 8 weeks.

Long-Term Maintenance Therapy in Patients with GERD

For long-term treatment of patients with GERD, the recommended dose is 10 mg* of omeprazole once daily. If necessary, the dose may be increased to 20–40 mg of omeprazole once daily.

Treatment of GERD Symptoms

For treatment of GERD symptoms, the recommended dose is 20 mg of omeprazole once daily. A dose of 10 mg* may be sufficient for some patients; dosage should be adjusted individually. If the desired effect is not achieved after 4 weeks of treatment with 20 mg of omeprazole daily, the patient should undergo further evaluation.

Zollinger–Ellison Syndrome Treatment

For patients with Zollinger–Ellison syndrome, dosage should be individually adjusted. Treatment continues until clinical manifestations resolve. The recommended initial dose is 60 mg of omeprazole once daily. Observations in over 90% of patients with severe disease and inadequate response to other therapies have shown efficacy of maintenance therapy with doses of 20–120 mg daily. Daily doses exceeding 80 mg should be divided and administered in two doses.

Paediatric Dosage

Children Aged 1 Year and Older with Body Weight ≥ 10 kg

Gastroesophageal Reflux Esophagitis

Symptomatic Treatment of Heartburn and Acid Regurgitation in GERD

Dosage Recommendations:

Age	Body weight	Dosage
≥ 1 year	10–20 kg	10 mg* once daily. If necessary, the dose can be increased to 20 mg once daily.
≥ 2 years	> 20 kg	20 mg once daily. If necessary, the dose can be increased to 40 mg once daily.

Treatment of reflux esophagitis: treatment duration is 4–8 weeks.

Symptomatic treatment of heartburn and acid regurgitation in GERD: treatment duration is 2–4 weeks. If the desired result is not achieved after 2–4 weeks, the patient should be further examined.

Children aged 4 years and adolescents.

Treatment of duodenal ulcer caused by H. pylori

When prescribing appropriate combination therapy, local patterns of bacterial resistance should be considered. The duration of treatment (7 to 14 days) and appropriate use of antibacterial agents must also be taken into account. Treatment should be conducted under medical supervision.

Dosing recommendations:

Body weight	Dosage
15–30 kg	Omeprazole 10 mg* + amoxicillin 25 mg/kg body weight + clarithromycin 7.5 mg/kg body weight. Take the medications together twice daily for 1 week
31–40 kg	Omeprazole 20 mg + amoxicillin 750 mg + clarithromycin 7.5 mg/kg body weight. Take the medications together twice daily for 1 week
> 40 kg	Omeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg. Take the medications together twice daily for 1 week

* If a dose of 10 mg is required, administer the drug in the appropriate dosage formulation.

Special patient groups

Renal impairment

Dose adjustment is not required in patients with renal impairment (see section "Pharmacokinetics").

Hepatic impairment

In patients with hepatic impairment, a daily dose of 10–20 mg is sufficient (see section "Pharmacokinetics").

Elderly patients (> 65 years of age)

Dose adjustment is not required in elderly patients (see section "Pharmacokinetics").

Method of administration

It is recommended to take the capsules in the morning, preferably before meals, without damaging the capsule (capsules must not be chewed or crushed), with half a glass of water.

The capsule should be taken immediately after opening the individual blister. Do not store the capsule outside the blister for later use.

For patients with swallowing difficulties and for children who can drink or swallow semisolid food. The capsules may be opened and the contents swallowed directly with half a glass of water, or mixed with a slightly acidic liquid such as fruit juice, apple puree, or non-carbonated water. This mixture should be taken immediately after preparation or within 30 minutes. The mixture should be shaken before administration and followed by half a glass of water.

Alternatively, patients may suck the capsule and swallow the granules, followed by half a glass of water. Granules with enteric coating must not be chewed.

Children

The medicinal product is prescribed by a physician for children from 1 year of age with body weight over 10 kg for the treatment of: gastroesophageal reflux disease (GERD), symptomatic treatment of heartburn and acid regurgitation associated with GERD, and for children from 4 years of age for the treatment of duodenal ulcer caused by H. pylori, under medical supervision.

Overdose

There are only limited data on omeprazole overdose in humans.

Isolated cases of overdose have been reported. A single dose of 560 mg of omeprazole has been documented, and there are data on single oral doses up to 2400 mg of omeprazole—120 times higher than the usual recommended dose.

Overdose occurs with a significant exceedance of the recommended single dose and is accompanied by symptoms such as nausea, vomiting, dizziness, abdominal pain, headache, and diarrhea. Isolated cases have also been associated with apathy, depression, and confusion. However, all reported symptoms were reversible, and no serious outcomes have been reported.

The elimination rate of the drug remains unchanged with increasing dose; therefore, specific treatment for overdose is not required.

There is no specific antidote. Omeprazole is highly protein-bound, so hemodialysis is ineffective. Symptomatic treatment is recommended.

Side effects

The most commonly reported side effects are headache, abdominal pain, constipation, diarrhoea, flatulence, and nausea/vomiting.

Adverse reactions are classified by system organ classes according to MedDRA and by frequency (very common: ≥ 1/10; common: from ≥ 1/100 to < 1/10; uncommon: from ≥ 1/1,000 to < 1/100; rare: from ≥ 1/10,000 to < 1/1,000; very rare: < 1/10,000), not known: cannot be estimated from available data.

Blood and lymphatic system disorders: rare: leucopenia, thrombocytopenia; very rare: agranulocytosis, pancytopenia.

Immune system disorders: rare: hypersensitivity reactions, including fever, angioneurotic oedema, and anaphylactic reactions/shock.

Metabolism and nutrition disorders: rare: hyponatraemia; frequency not known: hypomagnesaemia. Severe hypomagnesaemia may lead to hypocalcaemia; hypomagnesaemia may also cause hypokalaemia.

Psychiatric disorders: uncommon: insomnia; rare: agitation, confusion, depression; very rare: aggression, hallucinations.

Nervous system disorders: common: headache; uncommon: dizziness, paraesthesia, somnolence; rare: taste disturbance.

Eye disorders: rare: blurred vision.

Ear and labyrinth disorders: uncommon: vertigo.

Respiratory, thoracic and mediastinal disorders: rare: bronchospasm.

Gastrointestinal disorders: common: abdominal pain, constipation, diarrhoea, flatulence, nausea/vomiting; fundic gland polyps (benign); rare: dry mouth, stomatitis, gastrointestinal candidiasis; frequency not known: microscopic colitis.

Hepatobiliary disorders: uncommon: increased liver enzymes; rare: hepatitis with or without jaundice; very rare: hepatic failure, encephalopathy in patients with pre-existing liver disease.

Skin and subcutaneous tissue disorders: uncommon: dermatitis, pruritus, rash, urticaria; rare: alopecia, photosensitivity; very rare: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis; frequency not known: subacute cutaneous lupus erythematosus.

Musculoskeletal and connective tissue disorders: uncommon: fracture of hip, wrist or spine; rare: arthralgia, myalgia; very rare: muscle weakness.

Renal and urinary disorders: not known: interstitial nephritis (with possible progression to renal failure).

Reproductive system and breast disorders: very rare: gynaecomastia.

General disorders and administration site conditions: uncommon: malaise, peripheral oedema; rare: increased sweating; frequency not known: increased body temperature.

Children

The safety of omeprazole has been evaluated in 310 children aged from 0 to 16 years with acid-related disorders. Limited data are available on long-term safety in 46 children who received maintenance therapy with omeprazole for the treatment of severe erosive oesophagitis over 749 days. The adverse reaction profile is similar to that in adults during short- and long-term treatment. There are no long-term studies evaluating the effects of omeprazole treatment on sexual maturation and growth.

Shelf life. 2 years.

Storage conditions. Store at a temperature not exceeding 25 °C. Keep in the original packaging to protect from moisture.

Keep out of the reach of children.

Packaging.

7 capsules per blister, 4 blisters per carton; 14 capsules per blister, 2 blisters per carton.

Prescription status.

Prescription only

Manufacturer.

Laboratorios Liconsa, S.A.

Manufacturer's address.

Avda. Miralcampo, 7, Pol. Ind. Miralcampo, Azoqueca de Henares, Guadalajara, 19200, Spain.

Marketing Authorisation Holder.

LLC "ARTERIUM LTD"

Address of the Marketing Authorisation Holder.

139 Saksaganskogo St., Kyiv, 01032, Ukraine.