Omez capsules 40 mg No. 28

Instructions for Omez capsules 40 mg No. 28

Composition

active ingredient: omeprazole;

1 capsule contains omeprazole 40 mg;

Excipients: mannitol (E 421), crospovidone, poloxamer, hydroxypropylmethylcellulose, meglumine, povidone, methacrylate copolymer (type C), triethyl citrate, magnesium stearate.

Dosage form

Capsules.

Main physicochemical properties: off-white to light yellow elliptical and/or spherical shaped pellets in a hard opaque gelatin capsule size “0” with a yellow cap and lavender body with black inscription “OMEZ 40” on the cap and body of the capsule.

Pharmacotherapeutic group

Drugs for the treatment of peptic ulcer and gastroesophageal reflux disease. Proton pump inhibitors.

ATX code A02B C01.

Pharmacological properties

Pharmacodynamics

Mechanism of action: Omeprazole, a racemic mixture of two enantiomers, reduces gastric acid secretion by a targeted mechanism of action. It is a specific inhibitor of the gastric proton pump in parietal cells. It is rapidly acting and controls the reversible inhibition of gastric acid secretion when dosed once daily.

Omeprazole is a weak base that is concentrated and converted to the active form in the acidic environment of the intracellular tubules in parietal cells, where it inhibits the enzyme H+K+-ATPase - the acid pump. This effect on the final stage of the process of gastric acid formation is dose-dependent and provides highly effective inhibition 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.

Oral dosing of 20 mg omeprazole once daily causes rapid and effective inhibition of daytime and nighttime gastric acid secretion, with the maximum effect being achieved within 4 days of treatment. In patients with duodenal ulcer, a mean reduction in gastric acidity of approximately 80% occurs within 24 hours after taking 20 mg omeprazole, and a mean reduction in peak acid output after pentagastrin stimulation is approximately 70% 24 hours after taking omeprazole.

Oral dosing of 20 mg omeprazole maintains an intragastric pH of ≥ 3 in patients with duodenal ulcer for a mean of 17 hours out of a 24-hour period. Omeprazole reduces/normalizes esophageal acid exposure in patients with gastroesophageal reflux disease by dose-dependently reducing acid secretion and intragastric acidity. The inhibition of acid secretion is associated with the area under the plasma concentration-time curve (AUC) of omeprazole, not with the actual plasma concentration at a given time.

No tachyphylaxis was observed during treatment with omeprazole.

Effect on H. pylori.

Peptic ulcers are associated with H. pylori, including duodenal ulcers and gastric ulcers. H. pylori is considered a major determinant 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 gastric cancer.

The decrease in pH with the use of omeprazole and antimicrobials is associated with rapid relief of symptoms, a high percentage of healing of any mucosal lesions, and long-term remission of peptic ulcer disease.

Other effects are related to acid suppression.

A slightly increased incidence of gastric glandular cysts has been reported during long-term treatment. These changes are a physiological consequence of the existing inhibition of acid secretion, the cysts are benign and appear to be reversible.

Reducing stomach acid by any means, including proton pump inhibitors, increases the number of bacteria in the stomach that are normally present in the gastrointestinal tract. Treatment with acid-reducing drugs may lead to a slightly increased risk of gastrointestinal infections, such as those caused by Salmonella and Campylobacter.

Application in pediatrics.

In an uncontrolled study in children (aged 1 to 16 years) with severe erosive esophagitis, omeprazole at doses of 0.7–1.4 mg/kg improved the level of esophagitis in 90% of cases and significantly reduced reflux symptoms. In a blinded, non-comparative study, children aged 0 to 24 months with a diagnosis of gastroesophageal reflux disease were treated with doses of 0.5 mg/kg, 1.0 mg/kg and 1.5 mg/kg of omeprazole. The incidence of vomiting/regurgitation episodes was reduced by 50% after 8 weeks of treatment regardless of dose.

A randomized, double-blind clinical trial (Héliot study) concluded that omeprazole in combination with two antibiotics (amoxicillin and clarithromycin) was safe and effective in the treatment of H. pylori infection in children aged 4 years and older with gastritis: H. pylori eradication rate: 74.2% (23/31 patients) in the omeprazole+amoxicillin+clarithromycin group, compared with 9.4% (3/32 patients) in the amoxicillin+clarithromycin group. However, no evidence of clinical benefit was demonstrated for dyspeptic symptoms. This study does not include information on children aged under 4 years.

Pharmacokinetics

Absorption. Absorption of omeprazole is rapid, with peak plasma levels occurring 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 has no effect on bioavailability. The systemic availability (bioavailability) of omeprazole from a single oral dose of omeprazole is approximately 40%. After repeated once-daily administration, bioavailability increases to approximately 60%.

Distribution: The apparent volume of distribution in healthy subjects is approximately 0.3 l/kg body weight. The plasma protein binding of omeprazole is 97%.

Metabolism. Omeprazole is completely metabolised by the cytochrome P450 system. The majority of omeprazole metabolism is dependent on the expressed CYP2C19, responsible for the formation of hydroxyomeprazole, the major metabolite in plasma. The remainder is dependent on another specific isoform, CYP3A4, responsible for the formation of omeprazole sulfone. As a result of the high affinity of omeprazole for CYP2C19, there is a potential for competitive inhibition and metabolic interactions between drugs with other substrates for CYP2C19. However, due to its low affinity for CYP3A4, omeprazole has no potential to inhibit the metabolism of other CYP3A4 substrates. In addition, omeprazole has no inhibitory effect on major CYP enzymes.

Approximately 3% of the Caucasian population and 15–20% of Asian populations lack a functional CYP2C19 enzyme. In these individuals, the metabolism of omeprazole is likely to be 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 a functional CYP2C19 enzyme (extensive metabolizers). The mean peak plasma concentrations were also 3–5 times higher. These observations have no relevance to the dosing of omeprazole.

Elimination: The terminal half-life of omeprazole from plasma is generally less than 1 hour after both single and multiple once-daily oral dosing. Omeprazole is completely eliminated from plasma between doses without a tendency for accumulation during once-daily dosing. Approximately 80% of an oral dose of omeprazole is excreted as metabolites in the urine, the remainder in the faeces, mainly by biliary secretion.

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

The metabolite was not found to have any effect on gastric acid secretion.

Special populations: Hepatic impairment: In patients with hepatic impairment, the metabolism of omeprazole is altered, leading to an increase in AUC. Omeprazole did not show any tendency for accumulation with once-daily dosing.

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

Elderly patients: The metabolic rate of omeprazole is slightly reduced in elderly patients (75-79 years).

Children: When treated with recommended doses, plasma concentrations similar to those in adults were obtained in children from 1 year of age. In children under 6 months of age, clearance of omeprazole is low due to a low capacity to metabolize omeprazole.

Indication

Adult:

treatment and prevention of relapses of duodenal ulcers and benign gastric ulcers, including those associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs);

eradication of Helicobacter pylori (H. pylori) in peptic ulcer disease in combination with appropriate antibiotics;

treatment of gastroesophageal reflux disease, including reflux esophagitis;

treatment of Zollinger-Ellison syndrome

For children:

children aged 1 year and over and weighing more than 10 kg:

treatment of reflux esophagitis;

symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease.

Children aged 4 and over:

in combination with antibiotics for the treatment of duodenal ulcers caused by H. pylori.

Contraindication

Hypersensitivity to omeprazole, substituted benzimidazoles or to any of the excipients. Omeprazole, like other proton pump inhibitors (PPIs), should not be used concomitantly with nelfinavir (see Interactions with other medicinal products and other forms of interaction).

Interaction with other medicinal products and other types of interactions

Effect of omeprazole on the pharmacokinetics of other drugs.

Drugs whose absorption depends on the pH of the stomach.

Inhibition of gastric secretion by omeprazole and other PPIs may reduce or increase the absorption of drugs whose absorption depends on gastric pH. As with other drugs that reduce gastric acidity, the absorption of drugs such as ketoconazole, itraconazole and erlotinib may be reduced, while the absorption of drugs such as digoxin may be increased by omeprazole. Concomitant administration of omeprazole (20 mg daily) and digoxin in healthy volunteers increased the bioavailability of digoxin by 10% (in two out of ten subjects – up to 30%).

Nelfinavir, atazanavir.

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

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

Concomitant use of omeprazole with atazanavir is not recommended. Concomitant use of omeprazole (40 mg once daily) and atazanavir 300 mg/ritonavir 100 mg in healthy volunteers resulted in a 75% decrease in atazanavir exposure. Increasing the atazanavir dose to 400 mg did not compensate for the effect of omeprazole on atazanavir exposure. Concomitant use of omeprazole (20 mg once daily) with atazanavir 400 mg/ritonavir 100 mg in healthy volunteers resulted in an approximately 30% decrease in atazanavir exposure compared to atazanavir 300 mg/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%. Rare cases of digoxin-induced toxicity have been reported. However, caution should be exercised when prescribing high doses of omeprazole to elderly patients. Therapeutic drug monitoring of digoxin should be intensified.

Clopidogrel.

In a crossover clinical study, clopidogrel (300 mg loading dose followed by 75 mg/day) was administered as monotherapy and with omeprazole (80 mg co-administered with clopidogrel) for 5 days. When clopidogrel and omeprazole were co-administered, the exposure to the active metabolite of clopidogrel was reduced by 46% (day 1) and 42% (day 5). The mean inhibition of platelet aggregation was reduced by 47% (after 24 hours) and 30% (day 5) when clopidogrel and omeprazole were co-administered. In another study, it was shown that taking clopidogrel and omeprazole at different times did not prevent their interaction, which is likely due to the inhibitory effect of omeprazole on CYP2C19. Conflicting data regarding the clinical manifestations of this pharmacokinetic/pharmacodynamic (PK/PD) interaction in terms of major cardiovascular diseases have been reported in observational and clinical studies.

Other medicines.

The absorption of posaconazole, erlotinib, ketoconazole and itraconazole is significantly reduced and therefore clinical efficacy may be reduced. Concomitant use with posaconazole and erlotinib should be avoided.

Drugs metabolized by CYP2C19.

Omeprazole is a moderate inhibitor of CYP2C19, the main enzyme that metabolizes omeprazole. Therefore, the metabolism of concomitant drugs that are also metabolized by CYP2C19 may be reduced and the systemic exposure of these drugs may be increased. Examples of such drugs are R-warfarin and other vitamin K antagonists, cilostazol, diazepam and phenytoin.

In healthy volunteers, a pharmacokinetic/pharmacodynamic interaction was observed between clopidogrel (loading dose 300 mg/daily maintenance dose 75 mg) and omeprazole (80 mg/day orally, i.e. a dose 4 times the standard daily dose), resulting in a mean 46% decrease in exposure to the active metabolite of clopidogrel and a mean 16% decrease in the maximum inhibitory effect (induced by adenosine diphosphate (ADP)) on platelet aggregation. The clinical significance of this interaction remains unclear. As a precautionary measure, concomitant use of omeprazole and clopidogrel should be avoided.

Cilostazol.

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

Phenytoin.

Monitoring of phenytoin plasma concentrations is recommended during the first two weeks after starting treatment with omeprazole and, if phenytoin dose adjustment has been made, monitoring and further dose adjustment of the drug should be carried out after the end of treatment with omeprazole.

Unknown mechanism.

Saquinavir.

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

Increased serum tacrolimus levels have been reported with concomitant use of omeprazole. Increased monitoring of tacrolimus concentrations and renal function (creatinine clearance) is required and, if necessary, tacrolimus dosage should be adjusted.

Methotrexate

Increased methotrexate levels have been reported in some patients when co-administered with proton pump inhibitors. If high doses of methotrexate are necessary, temporary withdrawal of omeprazole should be considered.

Effect of other drugs on the pharmacokinetics of omeprazole.

CYP2C19 and/or CYP3A4 inhibitors.

Since omeprazole is metabolised by CYP2C19 and CYP3A4, drugs known to inhibit CYP2C19 or CYP3A4 or both (such as clarithromycin and voriconazole) may increase omeprazole serum levels by decreasing its metabolic rate. Concomitant use of voriconazole resulted in a more than two-fold increase in omeprazole exposure. Since high doses of omeprazole were well tolerated, dose adjustment of omeprazole is generally not necessary. However, dose adjustment should be considered in patients with severe hepatic impairment and if long-term treatment is indicated.

Omeprazole is also partially metabolized by CYP3A4, but does not inhibit this enzyme. Thus, omeprazole does not affect the metabolism of drugs metabolized by CYP3A4, such as cyclosporine, lidocaine, quinidine, estradiol, erythromycin, and budesonide.

CYP2C19 and/or CYP3A4 inducers.

Drugs known to induce the activity of CYP2C19 or CYP3A4 or both enzymes (such as rifampicin and St. John's wort) may lead to decreased serum levels of omeprazole as a result of an increased rate of its metabolism.

Application features

If any alarming symptom is present (e.g. significant weight loss not due to diet, frequent vomiting, dysphagia, haematemesis or melena) in a patient with or suspected of having a gastric ulcer, malignant disease should be excluded, as the use of the drug may mask its symptoms and delay the correct diagnosis.

Concomitant use of atazanavir with proton pump inhibitors is not recommended. If the combination of atazanavir with a proton pump inhibitor cannot be avoided, close clinical monitoring (e.g. viral load) is recommended in conjunction with an increase in the dose of atazanavir to 400 mg per 100 mg of ritonavir; the dose of omeprazole should not exceed 20 mg.

Omeprazole, like all drugs that inhibit the secretion of hydrochloric acid in the stomach, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be taken into account in patients with cachexia or risk factors for reduced absorption of vitamin B12 during long-term therapy.

Omeprazole is an inhibitor of CYP2C19. When initiating or discontinuing treatment with omeprazole, the possibility of interactions with medicinal products metabolised 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.

Patients taking proton pump inhibitors, including omeprazole, may develop significant hypomagnesemia for at least three months (in most cases of hypomagnesemia, patients have been taking the drug for about 1 year). Hypomagnesemia can be suspected by such serious manifestations as fatigue, muscle spasms, seizures, delirium, dizziness, ventricular arrhythmia. However, it should be borne in mind that in some cases the manifestations may be masked, which prevents timely recognition of such a complication. In most patients, the manifestations of hypomagnesemia disappear and the condition normalizes after the use of magnesium preparations and the withdrawal of proton pump inhibitors.

A prolonged decrease in gastric acidity can lead to an increase in the number of bacteria present in the gastrointestinal tract.

Treatment with proton pump inhibitors may lead to a slightly increased risk of developing gastrointestinal infections caused by Salmonella and Campylobacter.

In healthy volunteers, a pharmacokinetic/pharmacodynamic interaction was observed between clopidogrel (loading dose 300 mg/daily maintenance dose 75 mg) and omeprazole (80 mg/day orally, i.e. a dose 4 times the standard daily dose), resulting in a mean 46% decrease in exposure to the active metabolite of clopidogrel and a mean 16% decrease in the maximum inhibitory effect on (ADP-induced) platelet aggregation.

During treatment with antisecretory drugs, plasma gastrin concentrations increase as a result of decreased hydrochloric acid secretion. Decreased hydrochloric acid secretion results in increased chromogranin A (CgA) levels. Increased CgA levels may interfere with the results of tests for the detection of neuroendocrine tumors. To avoid such interference, the proton pump inhibitor should be discontinued 5 days before CgA measurements. If CgA and gastrin levels have not returned to the reference range after initial measurements, these measurements should be repeated 14 days after discontinuation of proton pump inhibitor treatment.

For the treatment of chronic diseases, children should not use the drug for longer than recommended.

As with all long-term treatments, especially when the treatment period lasts for more than 1 year, the patient should be under regular medical supervision.

Subacute cutaneous lupus erythematosus (SCL)

The use of proton pump inhibitors may be associated with very rare cases of PsA. If lesions occur, especially in sun-exposed areas of the skin, and if accompanied by arthralgia, the patient should seek medical advice immediately and the healthcare professional should consider discontinuing omeprazole. PsA following previous treatment with a proton pump inhibitor may increase the risk of PsA with other proton pump inhibitors.

Risk of allergic reactions

Omeprazole can cause serious skin reactions. Symptoms may include: skin redness, blistering, rash (see section "Side effects").

If the patient experiences an allergic reaction, he or she should stop taking the medication and seek medical attention immediately.

Kidney dysfunction

Acute tubulointerstitial nephritis (ATIN) has been reported in patients taking omeprazole. It can occur at any time during omeprazole therapy. Acute tubulointerstitial nephritis may progress to renal failure.

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

Use during pregnancy or breastfeeding

The results of studies indicate that omeprazole has no negative effects on pregnancy, the health of the fetus or the newborn. Omeprazole can be used during pregnancy if the expected benefit to the mother outweighs the possible risk to the fetus. Omeprazole passes into breast milk in small amounts, but its effect on the child is unknown, so breastfeeding should be discontinued during treatment with the drug.

Ability to influence reaction speed when driving vehicles or other mechanisms

The drug is unlikely to affect the ability to drive or use machines. Undesirable effects such as dizziness and visual disturbances may occur (see section "Adverse reactions"). If such disorders are observed, patients should not drive or use machines.

Method of administration and doses

Dosage for adults.

Treatment and prevention of duodenal ulcers and benign gastric ulcers, including those associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs).

The recommended dose for patients with duodenal ulcer is 20 mg omeprazole once daily. In most patients, duodenal ulcers heal within 2 weeks. For patients who do not fully heal after the initial course, further treatment for 2 weeks is recommended. In severe or recurrent cases, 40 mg omeprazole per day is recommended and healing is usually achieved within 4 weeks.

For the prevention of recurrence of duodenal ulcers in patients with a negative test result for H. pylori, the recommended dose is 20 mg omeprazole once daily. For some patients, a daily dose of 10 mg may be sufficient. In case of insufficient therapy, the dose can be increased to 40 mg.

In the treatment of gastric ulcers, the recommended dose is 20 mg omeprazole once daily. In most patients, gastric ulcers heal within 4 weeks. In patients who do not fully heal after the initial course, further treatment for 4 weeks is recommended. In severe or recurrent cases, 40 mg omeprazole per day is recommended, and healing is usually achieved within 8 weeks.

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

For the prevention of gastric and duodenal ulcers associated with the use of nonsteroidal anti-inflammatory drugs in patients at increased risk (age > 60, history of gastric and duodenal ulcers, upper gastrointestinal bleeding), the recommended dose is 20 mg omeprazole once daily.

Eradication of H. pylori in peptic ulcer.

When choosing antibacterial drugs for H. pylori eradication, individual drug tolerance should be considered and local treatment guidelines should be followed.

Omeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1000 mg 2 times a day 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) 2 times a day for 1 week, or

Omeprazole 40 mg once daily + amoxicillin 500 mg + metronidazole 400 mg (if necessary 500 mg or tinidazole 500 mg) 3 times daily for 1 week.

Treatment of gastroesophageal reflux disease, including reflux esophagitis.

The recommended dose is 20 mg omeprazole once daily. Most patients recover within 4 weeks. Patients who do not fully recover after the initial course are recommended to continue treatment for 4 weeks. For patients with severe esophagitis, 40 mg omeprazole daily is recommended, with recovery usually occurring within 8 weeks.

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

In the treatment of symptoms of gastroesophageal reflux disease, the recommended dose is 20 mg omeprazole once daily. The patient may be satisfied with a dose of 10 mg. The dose should be adjusted individually. If the desired result is not achieved after 4 weeks of treatment with omeprazole at a dose of 20 mg per day, the patient should be further examined.

Treatment of Zollinger-Ellison syndrome.

For patients with Zollinger-Ellison syndrome, the dose should be selected individually. Treatment is continued until clinical symptoms disappear. The recommended initial dose is 60 mg omeprazole once daily. Observation of more than 90% of patients with severe disease and insufficient response to other treatments has shown the effectiveness of maintenance therapy in doses of 20–120 mg per day. Daily doses above 80 mg should be divided and administered in 2 doses.

Dosage for children.

Children aged 1 year and over with a body weight ≥ 10 kg.

Treatment of reflux esophagitis.

Symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease.

Dosage recommendations:

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

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

Children and adolescents aged 4 years and over.

Treatment of duodenal ulcers caused by H. pylori.

The selection of appropriate combination therapy should be based on official national, regional and local guidelines on bacterial resistance. The duration of treatment (7 to 14 days) and the appropriate use of antibacterial agents should also be considered. Treatment should be carried out under the supervision of a physician.

Dosage recommendations:

If a dose of 10 mg or 20 mg is necessary, use the drug in the appropriate dosage.

Special patient groups.

Renal impairment: No dose adjustment is required for patients with renal impairment (see Pharmacokinetics).

Hepatic impairment: For patients with hepatic impairment, a daily dose of 10–20 mg is sufficient (see Pharmacokinetics).

Elderly patients (>65 years): No dose adjustment is required for elderly patients (see section 5.2).

For patients with swallowing difficulties and for children who can drink or swallow semi-solid food. The capsules can be opened and the contents swallowed directly with half a glass of water, or mixed in a slightly acidic liquid, such as any fruit juice or applesauce or unsalted water. This mixture should be drunk immediately after preparation or within 30 minutes. The mixture should be shaken before taking and washed down with half a glass of water. Do not use milk or carbonated water.

Children

The drug should be used in children over 1 year of age with a body weight of more than 10 kg as prescribed by a doctor for reflux esophagitis and symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease and in children over 4 years of age for the treatment of duodenal ulcers caused by the presence of H. pylori, under the supervision of a doctor.

Overdose

Data on the effects of omeprazole overdose in humans. There is very limited literature describing doses up to 560 mg of omeprazole, and there are isolated reports of single oral doses of 2400 mg of omeprazole (120 times the usual recommended clinical dose). Nausea, vomiting, dizziness, abdominal pain, diarrhea, and headache have been reported. Apathy, depression, and confusion have also been reported in isolated cases.

The described symptoms are transient in nature. The rate of elimination does not change (first-order kinetics) with increasing dose. Treatment, if necessary, is symptomatic.

Side effects

The most common adverse reactions are headache, abdominal pain, constipation, diarrhea, bloating, and nausea/vomiting. The following adverse drug reactions have been identified during clinical trials with omeprazole or during post-marketing use. Adverse reactions are classified according to their effect on organ systems.

From the blood and lymphatic system: leukopenia, thrombocytopenia, agranulocytosis, pancytopenia.

Immune system disorders: hypersensitivity reactions, e.g. fever, angioedema and anaphylactic reaction/shock.

Metabolism and digestion: hyponatremia, hypomagnesemia, severe hypomagnesemia may lead to hypocalcemia. Hypomagnesemia may also be associated with hypokalemia.

On the part of the psyche: insomnia, agitation, confusion, depression, aggression, hallucinations.

From the nervous system: headache, dizziness, paresthesia, drowsiness, taste disturbance.

From the organs of vision: blurred vision.

From the organs of hearing and balance: tinnitus, vertigo.

Respiratory, thoracic and mediastinal disorders: bronchospasm.

Gastrointestinal: abdominal pain, constipation, diarrhea, bloating, nausea/vomiting, dry mouth, stomatitis, gastrointestinal candidiasis, microscopic colitis, fundic gland polyps (benign).

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

Skin and subcutaneous tissue disorders: dermatitis, itching, skin redness, blisters, rash, urticaria, alopecia, photosensitivity, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, subacute cutaneous lupus erythematosus (see section "Special warnings and precautions for use").

Musculoskeletal system: arthralgia, myalgia, muscle weakness, increased risk of fractures with prolonged use (see section "Special instructions").

Renal and urinary disorders: tubulointerstitial nephritis (with possible progression to renal failure).

From the reproductive system and mammary glands: gynecomastia.

General disorders: discomfort, malaise, peripheral edema, increased sweating.

Pediatric patients.

The safety of omeprazole was assessed in 310 children aged 0 to 16 years with acid-dependent diseases. There are limited data on long-term safety studies in 46 children who received maintenance therapy with omeprazole in the treatment of severe