Omeprazole

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

Composition:

Active substance: omeprazole;

1 capsule contains omeprazole pellets calculated as omeprazole – 10 mg or 20 mg or 40 mg;

Excipients in the composition of pellets: sugar spheres (sucrose, maize starch), sodium lauryl sulfate, anhydrous sodium hydrogen phosphate, mannitol, hypromellose, polyethylene glycol 6000, talc, polysorbate 80, methacrylate copolymer dispersion, titanium dioxide (E 171);

Capsule shell composition:

10 mg – gelatin, iron oxide red (E 172), titanium dioxide (E 171);

20 mg – gelatin, azorubine (carmoisine) (E 122), iron oxide black (E 172), iron oxide red (E 172), titanium dioxide (E 171);

40 mg – gelatin, iron oxide yellow (E 172), titanium dioxide (E 171), iron oxide red (E 172).

Pharmaceutical form. Capsules.

Main physico-chemical properties:

10 mg. Hard gelatin capsules. Capsule body and cap are light pink in color. The capsule contents are pellets ranging from white to almost white-cream in color, spherical in shape, without visible defects;

20 mg. Hard gelatin capsules. Capsule body is white and cap is pink. The capsule contents are pellets ranging from white to almost white-cream in color, spherical in shape, without visible defects;

40 mg. Hard gelatin capsules. Capsule body is white and cap is beige. The capsule contents are pellets ranging from white to almost white-cream in color, spherical in shape, without visible defects.

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

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

Omeprazole is a racemic mixture of two enantiomers that reduces gastric acid secretion through a targeted mechanism of action. It is a specific inhibitor of the proton pump (PPI) in the parietal cells of the stomach. It acts rapidly and causes controlled, reversible inhibition of gastric acid secretion when administered once daily.

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

Pharmacodynamic effects

All observed pharmacodynamic effects can be explained by the effect of omeprazole on acid secretion.

Effect on gastric acid secretion

Once-daily oral administration of omeprazole results in rapid and effective inhibition of daytime and nighttime gastric acid secretion, with maximum effect achieved within 4 days of treatment. In patients with duodenal ulcer, mean reduction in gastric acidity (approximately 80%) occurs within 24 hours after administration of 20 mg omeprazole. The mean reduction in peak acid output after pentagastrin stimulation is about 70% at 24 hours after omeprazole administration.

Oral administration of 20 mg omeprazole maintains intragastric pH ≥ 3 for an average of 17 hours out of a 24-hour period in patients with duodenal ulcer.

Due to reduced acid secretion and intragastric acidity, omeprazole reduces/normalizes acid exposure in the esophagus in patients with gastroesophageal reflux disease (GERD), depending on the dose.

Inhibition of acid secretion correlates with the area under the plasma concentration-time curve (AUC) of omeprazole, rather than with the actual plasma concentration at any given time.

No tachyphylaxis has been observed during omeprazole treatment.

Effect on Helicobacter pylori (H. pylori)

Peptic ulcer disease, including duodenal ulcer and gastric ulcer, is associated with H. pylori. H. pylori is considered a major factor in the development of gastritis, and together with gastric acid, is a key factor in the development of peptic ulcer disease. H. pylori is also a primary factor in the development of atrophic gastritis, which is associated with an increased risk of gastric cancer.

Eradication of H. pylori using omeprazole in combination with antibiotics is associated with high cure rates and long-term remission of peptic ulcers.

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

Other effects related to acid suppression

During long-term treatment, a slightly increased incidence of glandular cysts in the stomach has been reported. These changes are a physiological consequence of acid secretion inhibition, the cysts are benign and reversible.

Reduced gastric acidity, caused by any means including PPIs, increases the number of bacteria normally present in the gastrointestinal tract. Treatment with acid-reducing agents slightly increases the risk of gastrointestinal infections, such as those caused by Salmonella and Campylobacter, and in hospitalized patients, possibly also those caused by Clostridium difficile.

During treatment with antisecretory drugs, plasma gastrin concentration increases as a result of reduced hydrochloric acid secretion. Due to reduced hydrochloric acid secretion, serum chromogranin A (CgA) levels increase. Elevated CgA levels may affect test results for detecting neuroendocrine tumors. Based on available published data, it is recommended that PPIs be discontinued 5 to 14 days before planned CgA measurements. This allows CgA levels, which may be falsely elevated after PPI use, to return to reference values.

During long-term omeprazole therapy, an increase in the number of enterochromaffin-like cells (ECL) has been observed in some patients (including both children and adults), possibly due 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 another study, infants aged 0 to 24 months with a clinically confirmed diagnosis of gastroesophageal reflux disease (GERD) 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.

Eradication of H. pylori in children

Clinical studies have shown that omeprazole in combination with two antibiotics (amoxicillin and clarithromycin) is safe and effective for treating H. pylori infection in children aged 4 years and older with gastritis. The H. pylori eradication rate was 74.2% with omeprazole + amoxicillin + clarithromycin compared to 9.4% with amoxicillin + clarithromycin alone. However, no clinical benefit regarding dyspeptic symptoms was demonstrated. Data on children under 4 years of age are lacking.

Pharmacokinetics.

Absorption

Omeprazole and omeprazole magnesium are acid-labile and therefore must be administered orally as enteric-coated granules in capsules or tablets. Omeprazole absorption is rapid, with peak plasma levels reached approximately 1–2 hours after dose administration. 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 about 60%.

Distribution

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

Biotransformation

Omeprazole is completely metabolized by the cytochrome P450 (CYP) system. The major part of its metabolism depends on the polymorphically expressed CYP2C19, responsible for the formation of hydroxyomeprazole, the main metabolite in plasma. Another part depends on a different specific isoenzyme, CYP3A4, responsible for the formation of omeprazole sulfone. Due to omeprazole's high affinity for CYP2C19, competitive inhibition and metabolic interactions between drugs that are substrates for CYP2C19 are possible. However, due to its low affinity for CYP3A4, omeprazole is not capable of inhibiting the metabolism of other CYP3A4 substrates. In addition, omeprazole does not inhibit major CYP enzymes.

Approximately 3% of individuals of Caucasian descent and 15–20% of individuals of Asian descent are poor metabolizers due to deficiency of functional CYP2C19 enzyme. In these individuals, omeprazole metabolism is likely catalyzed mainly by CYP3A4. After repeated administration of 20 mg omeprazole once daily, the AUC in poor metabolizers was 5–10 times higher than in subjects with functional CYP2C19 enzyme (extensive metabolizers). Mean peak plasma concentrations were also 3–5 times higher. These data do not affect omeprazole dosing.

Elimination

The plasma half-life of omeprazole is typically less than 1 hour, both after single and repeated once-daily dosing. Omeprazole is completely cleared from plasma between doses, with no tendency for accumulation when administered once daily. Nearly 80% of an oral dose of omeprazole is excreted in urine as metabolites; the remainder is excreted in feces via biliary secretion.

Linearity/Non-linearity

The AUC of omeprazole increases with repeated administration. This increase is dose-dependent and results in non-linear AUC-dose relationship after repeated dosing. This time- and dose-dependent relationship is due to reduced first-pass metabolism and systemic clearance, likely caused by inhibition of the CYP2C19 enzyme by omeprazole and/or its metabolites (e.g., sulfone).

No effect of omeprazole metabolites on gastric acid secretion has been observed.

Special patient groups

Hepatic impairment

Omeprazole metabolism is impaired in patients with hepatic dysfunction, leading to increased AUC. Omeprazole has not shown a tendency to accumulate when administered once daily.

Renal impairment

The pharmacokinetics of omeprazole, including systemic bioavailability and elimination rate, are not altered in patients with renal impairment.

Elderly patients

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

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

• Treatment of duodenal ulcers;
• Prevention of recurrence of duodenal ulcers;
• Treatment of gastric ulcers;
• Prevention of recurrence of gastric ulcers;
• In combination with appropriate antibiotics for eradication of Helicobacter pylori (H. pylori) 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 treatment of patients with healed reflux esophagitis to prevent relapse;
• Symptomatic treatment of gastroesophageal reflux disease (GERD);
• Treatment of Zollinger−Ellison syndrome.

Children

Children aged 1 year and older with body weight ≥ 10 kg

• Treatment of reflux esophagitis;
• Symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease.

Children aged 4 years and older and adolescents

• In combination with antibiotics for treatment of duodenal ulcer caused by H. pylori.

Contraindications.

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

Omeprazole, like other PPIs, must not be used concomitantly with nelfinavir (see section "Interaction with other medicinal products and other forms of interaction").

Interaction with other medicinal products and other forms of interaction.

Effect of omeprazole on the pharmacokinetics of other medicinal products

Medicinal products whose absorption is pH-dependent

Suppression of gastric acid secretion during omeprazole treatment may decrease or increase the absorption of medicinal products whose absorption is pH-dependent.

Nelfinavir, atazanavir

Plasma levels of nelfinavir and atazanavir are reduced when co-administered with omeprazole.

Concomitant use of omeprazole and nelfinavir is contraindicated, as administration of omeprazole (40 mg once daily) reduced the mean AUC of nelfinavir by approximately 40% and the mean AUC of its pharmacologically active metabolite M8 by 75–90%. The interaction may also be due to inhibition of CYP2C19 activity.

Concomitant use of omeprazole with atazanavir is not recommended. Concomitant administration of omeprazole (40 mg once daily) and atazanavir 300 mg or ritonavir 100 mg in healthy volunteers resulted in a 75% reduction in atazanavir AUC. Increasing the atazanavir dose to 400 mg did not compensate for the effect of omeprazole on atazanavir AUC. Concomitant administration of omeprazole (20 mg once daily) with atazanavir 400 mg or ritonavir 100 mg in healthy volunteers resulted in approximately a 30% reduction in atazanavir AUC compared to atazanavir 300 mg or ritonavir 100 mg once daily.

Digoxin

Concomitant treatment with omeprazole (20 mg daily) and digoxin in healthy volunteers increased the bioavailability of digoxin by 10%. Cases of digoxin toxicity have been rarely reported. However, caution should be exercised when prescribing high doses of omeprazole to elderly patients. Therapeutic monitoring of digoxin should be intensified.

Clopidogrel

A pharmacokinetic (PK)/pharmacodynamic (PD) interaction between clopidogrel (loading dose 300 mg/daily maintenance dose 75 mg) and omeprazole (80 mg daily orally) was observed in healthy volunteers, resulting in a mean reduction of 46% in the AUC of the active metabolite of clopidogrel and a mean reduction of 16% in maximum inhibitory effect (ADP-induced) on platelet aggregation.

Conflicting data on the clinical implications of this PK/PD interaction regarding major cardiovascular events have been obtained from observational and clinical studies. As a precautionary measure, concomitant use of omeprazole and clopidogrel should be avoided.

Other medicinal products

Absorption of posaconazole, erlotinib, ketoconazole, and itraconazole is significantly reduced, and thus clinical efficacy may be diminished. Concomitant use with posaconazole and erlotinib should be avoided.

Medicinal products metabolized by CYP2C19

Omeprazole has a moderate inhibitory effect on CYP2C19 (the main enzyme responsible for omeprazole metabolism). Therefore, metabolism of concomitantly administered medicinal products that are also metabolized by CYP2C19 may be reduced, and systemic exposure to these agents may increase. Examples include R-warfarin and other vitamin K antagonists, cilostazol, diazepam, and phenytoin.

Cilostazol

In healthy volunteers, administration of omeprazole 40 mg increased the maximum plasma concentration (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 plasma concentration is recommended during the first two weeks after initiation of omeprazole treatment. If phenytoin dosage adjustment is required, monitoring and further dosage adjustments should be performed after discontinuation of omeprazole treatment.

Unknown mechanism

Saquinavir

Concomitant administration of omeprazole with saquinavir/ritonavir resulted in an increase in saquinavir plasma levels by approximately 70%, which was associated with acceptable tolerability in HIV-infected patients.

Tacrolimus

Elevated serum levels of tacrolimus have been reported with concomitant use of omeprazole. Intensified monitoring of tacrolimus concentration and renal function (creatinine clearance) is required, and dosage adjustment of tacrolimus may be necessary.

MTX (Methotrexate)

Elevated methotrexate levels have been reported in some patients receiving concomitant PPIs. In cases where high-dose methotrexate is required, temporary discontinuation of omeprazole should be considered.

Effect of other medicinal products on the pharmacokinetics of omeprazole

Inhibitors of CYP2C19 and/or CYP3A4

Since omeprazole is metabolized by CYP2C19 and CYP3A4 enzymes, drugs that inhibit CYP2C19 or CYP3A4 activity (such as clarithromycin and voriconazole) may increase omeprazole serum levels due to slowed metabolism. Concomitant administration of voriconazole resulted in more than a two-fold increase in omeprazole AUC. As high doses of omeprazole are generally well tolerated, dose adjustment of omeprazole is usually not required. However, dose adjustment should be considered in patients with severe hepatic impairment and during long-term treatment.

Inducers of CYP2C19 and/or CYP3A4

Drugs that induce CYP2C19 or CYP3A4 activity, or both enzymes (such as rifampicin and St. John's wort), may reduce omeprazole serum levels due to accelerated metabolism.

Special precautions for use.

In the presence of any alarming symptom (e.g., significant unintentional weight loss, frequent vomiting, dysphagia, hematemesis, or melena) and in diagnosed or suspected gastric ulcer, malignancy should be ruled out, as drug administration may mask symptoms and delay correct 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) in combination 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 low body weight or risk factors for reduced vitamin B12 absorption during long-term therapy.

Omeprazole is an inhibitor of CYP2C19. At the initiation or termination of omeprazole treatment, potential interactions with medicinal products metabolized by CYP2C19 should be considered. An interaction has been observed between clopidogrel and omeprazole. The clinical significance of this interaction remains unclear. As a precautionary measure, concomitant use of omeprazole and clopidogrel should be avoided.

In patients who have taken PPIs, including omeprazole, for at least 3 months, severe hypomagnesemia has occurred (in most cases, patients had been taking the drug for approximately one year). Hypomagnesemia may present with serious symptoms such as fatigue, tetany, delirium, seizures, dizziness, and ventricular arrhythmias. Hypomagnesemia may also be asymptomatic and may remain undiagnosed. In most patients, symptoms of hypomagnesemia resolve and magnesium levels normalize after magnesium supplementation and discontinuation of PPI.

In patients planned for long-term PPI therapy or concomitant use of digoxin or other medicinal products that may cause magnesium depletion (e.g., diuretics), serum magnesium concentration should be measured before starting PPI treatment and periodically during therapy.

PPIs, particularly when used at high doses and for prolonged periods (>1 year), are associated with a slightly increased risk of fractures of the spine, wrist, and hip, especially in elderly patients and in the presence of predisposing factors. According to observational studies, PPIs increase the overall fracture risk by 10–40%. The increased risk may be partially related to other factors. Patients at risk of developing osteoporosis should receive appropriate management according to current clinical guidelines and should consume adequate amounts of vitamin D and calcium.

Subacute cutaneous lupus erythematosus (SCLE)

PPI use has occasionally been associated with the development of SCLE. If skin manifestations appear, particularly in sun-exposed areas, and are accompanied by arthralgia, patients should seek immediate medical advice and discontinuation of omeprazole should be considered. A history of SCLE following PPI use increases the risk of SCLE with other PPIs.

Renal function

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.

Effect on laboratory test results

Elevated chromogranin A (CgA) levels may interfere with investigations for neuroendocrine tumors. To obtain accurate results, omeprazole should be temporarily discontinued 5 days before CgA measurement. If CgA and gastrin levels do not return to reference ranges after initial testing, these parameters should be re-measured 14 days after discontinuation of PPI therapy.

Some children with chronic diseases may require long-term treatment, although such treatment is not recommended.

PPI therapy slightly increases the risk of gastrointestinal infections, such as those caused by Salmonella and Campylobacter, and in hospitalized patients, possibly also those caused by Clostridium difficile.

Patients who use the drug for a prolonged period (especially if treatment lasts more than 1 year) require regular medical monitoring.

The drug should not be used in patients with known hypersensitivity to omeprazole. Omeprazole may cause serious skin reactions. Symptoms may include skin redness, blisters, and rash. In the event of an allergic reaction, the drug should be discontinued and immediate medical attention sought.

Omeprazole, 20 mg capsules, contain carmoisine (E 122), which may cause allergic reactions.

The medicinal product contains sucrose; therefore, if the patient has been diagnosed with intolerance to certain sugars, consultation with a physician is recommended before taking this medicinal product.

This medicinal product contains less than 1 mmol per dose of sodium, i.e., essentially "sodium-free".

Use during pregnancy or breastfeeding.

Pregnancy

Results from prospective epidemiological studies indicate no adverse effects of omeprazole on pregnancy or fetal/newborn health. Omeprazole may be used during pregnancy.

Breastfeeding

Omeprazole passes into breast milk, but the likelihood of effects on the infant is low when used at therapeutic doses.

Fertility

Oral administration of racemic omeprazole in animal studies did not affect reproductive function.

Ability to influence reaction rate when driving or operating machinery.

It is unlikely that omeprazole affects the ability to drive or operate machinery. Adverse reactions such as dizziness and visual disturbances may occur. If such disorders occur, patients should not drive or operate machinery.

Administration and Dosage.

Dosage

Adults

Treatment of duodenal ulcer

The recommended dose for patients with active duodenal ulcer is 20 mg of omeprazole once daily. In most patients, duodenal ulcer heals within 2 weeks. For patients who do not achieve complete healing 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 ulcer

For prevention of recurrence of duodenal ulcer in patients with a negative H. pylori test, the recommended dose is 20 mg of omeprazole once daily. A daily dose of 10 mg may be sufficient for some patients. In case of inadequate response, the dose may be increased to 40 mg.

Treatment of gastric ulcer

The recommended dose is 20 mg of omeprazole once daily. In most patients, gastric ulcer heals within 4 weeks. Patients who do not achieve complete healing after the initial course should be treated further for 4 weeks. In severe cases or cases of recurrence, 40 mg of omeprazole once daily is recommended, with healing usually achieved within 8 weeks.

Prevention of recurrence of gastric ulcer

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

H. pylori eradication in peptic ulcer disease

For H. pylori eradication, when selecting antibacterial agents, individual drug tolerability, relevant national and local guidelines and treatment recommendations should be considered:

• 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.

If, after any regimen, the patient remains H. pylori-positive, therapy may be repeated.

Treatment of NSAID-associated gastric and duodenal ulcers

For treatment of gastric and duodenal ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs), the recommended dose is 20 mg of omeprazole once daily. Healing is achieved in most patients within 4 weeks. Patients who do not achieve complete healing after the initial course should be treated further for 4 weeks.

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

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

Treatment of reflux esophagitis

The recommended dose is 20 mg of omeprazole once daily. Healing is achieved in most patients within 4 weeks. Patients who do not achieve complete healing after the initial course should be treated further for 4 weeks.

In patients with severe esophagitis, the recommended dose is 40 mg of omeprazole once daily, with healing usually achieved within 8 weeks.

Long-term treatment of patients with healed reflux esophagitis

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

Treatment of symptomatic gastroesophageal reflux disease

The recommended dose is 20 mg of omeprazole once daily. For some patients, a daily dose of 10 mg may be sufficient; therefore, the dose should be individualized.

If symptoms do not resolve after 4 weeks of treatment with 20 mg omeprazole daily, further patient evaluation is required.

Treatment of Zollinger–Ellison syndrome

For patients with Zollinger–Ellison syndrome, dosage should be individualized. Treatment continues until clinical manifestations disappear. The recommended initial dose of omeprazole is 60 mg once daily. Observations in more than 90% of patients with severe disease and poor response to other treatments have shown the effectiveness of maintenance therapy with omeprazole at doses of 20–120 mg daily. Daily omeprazole doses exceeding 80 mg should be divided and administered in two doses.

Children

Children aged 1 year and older with body weight ≥ 10 kg

Treatment of reflux esophagitis

Symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease

Dosage recommendations:

Gastroesophageal reflux disease (GERD): treatment duration is 4–8 weeks.

Symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease: treatment duration is 2–4 weeks. If the desired therapeutic effect is not achieved after 2–4 weeks, the patient should undergo further diagnostic evaluation.

Adolescents and children aged 4 years and older

Treatment of H. pylori-associated duodenal ulcer.

Combined therapy should be prescribed according to national and local guidelines regarding bacterial resistance patterns. Treatment duration (from 7 to 14 days) and appropriate use of antibacterial agents must also be considered.

Treatment must be conducted under medical supervision.

Dosing recommendations:

Special populations

Renal impairment

Dose adjustment is not required in patients with renal impairment.

Hepatic impairment

A daily dose of 10–20 mg is sufficient for patients with hepatic impairment.

Elderly patients

Elderly patients do not require dose adjustment.

Administration method

It is recommended to take Omeprazole capsules in the morning, swallowing them whole with half a glass of water. The capsules must not be chewed or crushed.

For patients with swallowing difficulties and for children who can drink or swallow semisolid food

The capsules may be opened and the contents swallowed immediately with half a glass of water, or mixed in a slightly acidic liquid, such as any fruit juice, apple puree, or unsalted water. This mixture must be taken immediately after preparation or within 30 minutes. Before administration, the mixture should be stirred and followed by half a glass of water.

Alternatively, the capsules may be sucked, then the contents swallowed with half a glass of water. The gastroresistant granules must not be chewed.

The capsule must be taken immediately after opening the individual blister. Capsules should not be stored outside the blister for later use.

Children

The medicinal product may be administered to children aged 1 year and older with body weight above 10 kg, as prescribed by a physician, for the treatment of reflux esophagitis and symptomatic relief of heartburn and acid regurgitation in gastroesophageal reflux disease, and to children aged 4 years and older for the treatment of duodenal ulcer associated with H. pylori, under medical supervision.

Overdose

Data on the effects of omeprazole overdose in humans are very limited. Doses up to 560 mg of omeprazole have been described in the scientific literature, and there have been isolated reports of single oral doses reaching 2400 mg of omeprazole (120 times higher than the usual recommended clinical dose). Symptoms reported include nausea, vomiting, dizziness, abdominal pain, diarrhea, and headache. In isolated cases, lethargy, depression, and confusion have also been reported.

However, all reported symptoms were transient, and no serious consequences were reported. Drug elimination rate was not altered (first-order kinetics) with increasing dose. If necessary, symptomatic treatment should be administered.

Adverse reactions.

The most common adverse effects (in 1–10 % of patients) are headache, abdominal pain, constipation, diarrhea, bloating, and nausea/vomiting.

The adverse reactions listed below were identified or suspected during clinical trials or post-marketing use of omeprazole. These were found not to be dose-dependent. Adverse reactions are classified by organ systems. Frequency is defined as follows: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10000, < 1/1000); very rare (< 1/10000); frequency not known (cannot be estimated from available data).

Children

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

Reporting suspected adverse reactions

Reporting of suspected adverse reactions following marketing authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients or their legal representatives are encouraged to report any suspected adverse reactions and lack of efficacy through the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions. Store at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Packaging.

10 mg capsules: 7 capsules in a blister; 2 or 4 blisters in a carton.

20 mg or 40 mg capsules: 7 capsules in a blister; 1 or 4 blisters in a carton; 10 capsules in a blister; 1 or 3 blisters in a carton.

Prescription status. Prescription only.

Manufacturer. JSC "Farmak".

Manufacturer's address and location of its business operations.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.