Gastrozole, capsules 20mg, 28pcs

Composition

Omeprazole – 235,0 mg (in the form of a pellet that contains: Active ingredient: omeprazole – 20,0 mg;

excipients: mannitol – 39,95 mg, sucrose – 64,2255 mg, sodium lauryl sulfate – 0,799 mg, sodium hydrogen phosphate (sodium phosphate, disodium) – 2,9845 mg, calcium carbonate 7,99 mg, lactose monohydrate – 7,99 mg, hypromellose (hydroxypropyl methylcellulose) – 20,5625 mg methacrylic acid copolymer ethylacrylate [1: 1] – 58,75 mg, propylene glycol – 1,9035 mg, diethyl – 5,875 mg, cetyl alcohol 1,7625 mg sodium hydroxide – 0,3525 mg, Polysorbate-80 (tween-80) – 0,705 mg, povidone (polyvinylpyrrolidone) – 0,611 mg, titanium dioxide – 0,423 mg, talc – 0,141 mg)

Solid gelatin capsules – 63.0 mg: body: titanium dioxide (E 171) – 2.0000%, gelatin – up to 100%; cap: titanium dioxide (E 171) – 2.0000%, iron oxide red dye (E 172) -0.7286%, gelatin-up to 100%.

Pharmacological action

Pharmacotherapeutic group: a means of reducing the secretion of gastric glands-proton pump inhibitor

ATX code: A 02 BC 01

Pharmacological properties

Pharmacodynamics

Mechanism of action

Omeprazole is a weak base. It is concentrated in the acidic environment of the secretory tubules of the parietal cells of the gastric mucosa, is activated and inhibits the proton pump-the enzyme H+, K+ – ATPase. The effect of omeprazole on the last stage of the formation of hydrochloric acid in the stomach is dose-dependent and provides highly effective inhibition of basal and stimulated hydrochloric acid secretion, regardless of the stimulating factor.

Effect on gastric juice secretion

Omeprazole with daily oral use provides rapid and effective inhibition of day and night secretion of hydrochloric acid.

The maximum effect is achieved after 4 days of treatment. In patients with duodenal ulcer, omeprazole 20 mg causes a steady decrease in 24-hour gastric acidity by at least 80%. In this case, the average maximum concentration of hydrochloric acid after stimulation with pentagastrin is reduced by 70% within 24 hours.

In patients with duodenal ulcers, a daily dose of 20 mg of omeprazole maintains an intragastric pH of ≥ 3 for 17 hours per day. Inhibition of hydrochloric acid secretion depends on the area under the concentration-time curve (AUC) of omeprazole, and not on the concentration of the drug in the blood plasma at a given time.

Action on Helicobacter Pylori

Omeprazole has a bactericidal effect on Helicobacterpyloriinvitro.

Eradication of Helicobacter Pylori when using omeprazole together with antibacterial agents is accompanied by rapid elimination of symptoms, a high degree of healing of defects in the gastrointestinal mucosa and long-term remission of peptic ulcer disease, which reduces the likelihood of complications such as bleeding, as effective as constant maintenance therapy.

Other effects associated with inhibition of hydrochloric acid secretion

Patients taking drugs that reduce the secretion of gastric glands for a long period of time are more likely to develop benign gastric cysts that pass on their own against the background of continuing therapy. These phenomena are caused by physiological changes resulting from inhibition of hydrochloric acid secretion.

A decrease in the secretion of hydrochloric acid in the stomach under the action of proton pump inhibitors or other acid-inhibiting agents leads to an increase in the growth of normal intestinal microflora, which in turn can lead to a slight increase in the risk of intestinal infections caused by Salmonellaspp bacteria. and Campylobacter Spp., and in hospitalized patients also probably with the bacterium Clostridium difficile.

During treatment with drugs that lower the secretion of gastric glands, the concentration of gastrin in the blood serum increases. Due to a decrease in the secretion of hydrochloric acid, the concentration of chromogranin A (DdA) increases.

In children and adult patients who took omeprazole for a long time, an increase in enterochromaffin-like cells was observed, probably associated with an increase in the concentration of gastrin in the blood serum. This phenomenon has no clinical significance.

Pharmacokinetics

Distribution

Omeprazole is absorbed in the small intestine, usually within 3-6 hours, the time to reach the maximum concentration (Tc_max) is 0.5-3.5 hours. Bioavailability after a single oral dose is approximately 30-40%, after a constant intake of 1 time per day, the bioavailability increases to 60%. Food intake does not affect the bioavailability of omeprazole.

The binding rate of omeprazole to plasma proteins is about 95%, the volume of distribution is 0.3 l / kg.

Metabolism

It is almost completely metabolized in the liver. The main enzymes involved in the metabolic process are CYP2C19 and CYP2A4. The resulting metabolites-sulfone and sulfide-do not significantly affect the secretion of hydrochloric acid. It is an inhibitor of the CYP2C19 isoenzyme.

Excretion

The elimination half-life is about 40 minutes (30-90 minutes). About 80% is excreted as metabolites by the kidneys, and the rest is excreted through the intestines.

Special patient groups

There were no significant changes in the bioavailability of omeprazole in elderly patients or in patients with impaired renal function. In patients with impaired liver function, there is an increase in the bioavailability of omeprazole and a significant decrease in plasma clearance.

Indications

Adults

-duodenal ulcer

– gastric

ulcer – NSAIDs associated ulcers and erosions of the stomach and duodenum – Helicobacter pylori eradication in peptic ulcer disease

-reflux esophagitis

-symptomatic gastro-esophageal reflux disease (GERD)

– dyspepsia associated with high acidity

– Zollinger-Ellison syndrome

Children

-gastroesophageal reflux disease in children older than 2 years

– duodenal ulcer associated with Helicobacter Pylori (as part of combination therapy), in children older than 4 years.

Use during pregnancy and lactation

Pregnancy

The results of the studies showed no side effects of omeprazole on the health of pregnant women, on the fetus or newborn. Omeprazole can be used during pregnancy.

Breast-feeding

Omeprazole penetrates into breast milk, the use of omeprazole during breastfeeding is contraindicated.

Contraindications

• Hypersensitivity to omeprazole, substituted benzimidazoles or others in gredients that are part of the product;

• the deficiency of lactase, sucrase/isomaltase, lactose intolerance, fructose, glucose-galactosaminidase;

• joint application with erlotinib, Posaconazole, clarithromycin by (in patients with hepatic insufficiency), St. John’s wort;

• lactation;

• children up to age 18 years, with the exception of:

– gastroesophageal reflux disease

-children under 2 years of age and body weight up to 20 kg;

– duodenal ulcer associated with Helicobacter

Pylori – children under 4 years of age and body weight less than 31 kg.

With caution

Osteoporosis, significant spontaneous weight loss, frequent vomiting, dysphagia, vomiting with blood or melena, as well as in the presence of a stomach ulcer (or suspected stomach ulcer), pregnancy. It is necessary to exclude the presence of malignancy, since treatment may mask the symptoms and, thus, delay the diagnosis.

Side effects

The following are side effects that are independent of the dosage regimen of omeprazole, which were noted in clinical studies, as well as in post-marketing use. The following adverse events reported with omeprazole are distributed according to the frequency of occurrence in accordance with the following gradation: very common (> 1/10), common (>1/100 to > < 1/10), infrequent (> 1/1000 to < 1/10), infrequent (>1/100), rare (> 1/10000 to<1/100), rare (>1/1000), very rare (

From the digestive system: often – diarrhea, constipation, abdominal pain, nausea, vomiting, flatulence; rarely-dry mouth, stomatitis, candidiasis of the gastrointestinal tract, microscopic colitis.

From the liver and biliary tract: infrequently-increased activity of “liver” enzymes; rarely-hepatitis (with or without jaundice), liver failure, encephalopathy in patients with liver diseases.

Hematopoietic disorders: rarely-leukopenia, thrombocytopenia, agranulocytosis, pancytopenia, hypochromic microcytic anemia in children.

From the nervous system: often-headache; infrequently-vertigo, paresthesia, drowsiness; rarely-taste disorders.

From the musculoskeletal system: infrequently-fractures of the hip, wrist bones and vertebrae; rarely-arthralgia, myalgia, muscle weakness.

Skin and subcutaneous tissue disorders: infrequently-dermatitis, rash, pruritus, urticaria; rarely-alopecia, photosensitization, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

From the immune system: rarely – hypersensitivity reactions (for example, angioedema, fever, anaphylactic reaction/anaphylactic shock).

From the side of metabolism and nutrition: rarely-hyponatremia; very rarely-hypocalcemia due to severe hypomagnesemia, hypokalemia due to hypomagnesemia; unspecified frequency-hypomagnesemia.

From the side of the psyche: infrequently-insomnia; rarely-agitation, aggression, confusion, hallucinations, depression.

From the side of the organ of vision: rarely-blurred vision.

Respiratory, thoracic and mediastinal disorders: rarely-bronchospasm.

From the side of the kidneys and urinary tract: rarely-interstitial nephritis.

From the genitals and breast: rarely-gynecomastia.

General disorders and disorders at the injection site: infrequently-malaise; rarely-sweating, peripheral edema.

Cases of glandular gastric disorders have been reported in patients taking drugs that reduce the secretion of the pancreas for a long period of time; they pass independently on the background of continuing therapy.

Interaction

Effect of omeprazole on the pharmacokinetics of other medicinal products Reduced secretion of hydrochloric acid in the stomach during treatment with omeprazole and other proton pump inhibitors may lead to a decrease or increase in the absorption of other drugs, the absorption of which depends on the acidity of the medium.

As with other drugs that inhibit the secretion of hydrochloric acid or antacids, treatment with omeprazole may lead to a decrease in the absorption of erlotinib, ketoconazole or itraconazole, as well as an increase in the absorption of digoxin. Concomitant use of omeprazole (at a dose of 20 mg per day) and digoxin results in a 10% increase in the bioavailability of digoxin.

Omeprazole has been shown to interact with some antiretroviral drugs. The mechanisms and clinical significance of these interactions are not always known. An increase in the pH value during omeprazole therapy may affect the absorption of antiretroviral drugs.

Interaction at the level of the CYP2C19 isoenzyme is also possible. When omeprazole is co-administered with some antiretroviral drugs, such as atazanavir and nelfinavir, a decrease in their serum concentrations is observed during omeprazole therapy. Therefore, co-use of omeprazole with antiretroviral drugs such as atazanavir and nelfinavir is not recommended.

When omeprazole and saquinavir were co-administered, an increase in the concentration of saquinavir in the serum was noted, while when used with some other antiretroviral drugs, their concentration did not change.

Omeprazole inhibits CYP2C19, the main isoenzyme involved in its metabolism. Concomitant use of omeprazole with other drugs that are metabolized by the CYP2C19 isoenzyme, such as diazepam, warfarin (R-warfarin) or other vitamin K antagonists, phenytoin and cilostozol, may slow down the metabolism of these drugs.

It is recommended to monitor patients taking phenytoin and omeprazole, it may be necessary to reduce the dose of phenytoin. However, concomitant treatment with omeprazole at a daily dose of 20 mg does not affect the concentration of phenytoin in blood plasma in patients taking the drug for a long time.

When using omeprazole in patients receiving warfarin or other vitamin K antagonists, monitoring of the international normalized ratio is necessary; in some cases, it may be necessary to reduce the dose of warfarin or another vitamin K antagonist.

At the same time, concomitant treatment with omeprazole at a daily dose of 20 mg does not change the coagulation time in patients taking warfarin for a long time.

The use of omeprazole at a dose of 40 mg once a day resulted in an increase in the_cmaxand AUC of cilostazol by 18% and 26%, respectively; for one of the active metabolites of cilostazol, the increase was 29% and 69%, respectively.

The results of the trials showed a pharmacokinetic/pharmacodynamic interaction between clopidogrel (loading dose of 300 mg and a maintenance dose of 75 mg/day) and omeprazole (80 mg/day orally), which leads to a decrease in exposure to the active metabolite of clopidogrel by an average of 46% and a decrease of the maximal inhibition of ADP-induced platelet aggregation on average 16%.

The clinical significance of this interaction is not clear. An increased risk of cardiovascular complications with the combined use of clopidogrel and proton pump inhibitors, including omeprazole, has not been shown in randomized clinical trials.

The results of a number of observational studies are contradictory and do not provide an unambiguous answer about the presence or absence of an increased risk of thromboembolic cardiovascular complications with the combined use of clopidogrel and proton pump inhibitors.

Omeprazole does not affect the metabolism of drugs metabolized by the CYP3A4 isoenzyme, such as cyclosporine, estradiol, budesonide, quinidine, lidocaine.

Omeprazole did not interact with the following drugs: antacids, theophylline, caffeine, propranolol, ethanol, S-warfarin, piroxicam, diclofenac, naproxen, metoprolol.

When omeprazole and tacrolimus were co-administered, an increase in the concentration of tacrolimus in the blood serum was noted.

In some patients, a slight increase in the concentration of methotrexate in blood plasma has been reported when it is co-administered with proton pump inhibitors. When using high doses of methotrexate, omeprazole should be temporarily discontinued.

Effect of medicinal products on the pharmacokinetics of omeprazole

The isoenzymes CYP2C19 and CYP3A4 are involved in the metabolism of omeprazole. Concomitant use of omeprazole and inhibitors of the CYP2C19 and CYP3A4 isoenzymes, such as clarithromycin, erythromycin, and voriconazole, may increase the concentration of omeprazole in blood plasma by slowing down the metabolism of omeprazole.

The combined use of omeprazole and voriconazole leads to a more than twofold increase in the AUC of omeprazole. Due to the good tolerability of high doses of omeprazole, with short-term co-use of these drugs, no dose adjustment of omeprazole is required.

Drugs that induce CYP2C19 and CYP3A4 isoenzymes, such as rifampicin and St. John’s wort preparations, when combined with omeprazole, can lead to a decrease in its concentration in blood plasma due to the acceleration of drug metabolism.

Co-use of omeprazole with amoxicillin or metronidazole does not affect the concentration of omeprazole in blood plasma.

How to take, course of use and dosage

The drug is taken orally, capsules are not chewed, usually in the morning, washed down with a small amount of water (just before meals or during meals).

For patients with difficulty swallowing and for children who cannot swallow the capsule: You should open the capsule and swallow the contents with 100 ml of warm water.

Or mix the contents of the capsule with an acidic liquid, such as apple juice or still water. patients should be advised that the resulting dispersion solution should be taken immediately (within 30 minutes) and mixed immediately before use.

Adults

Duodenal ulcer

Patients with active duodenal ulcer should take omeprazole 1 capsule (20 mg) once a day. The drug provides rapid elimination of symptoms. In most patients, ulcer healing occurs within 2 weeks. In cases where complete healing of the ulcer does not occur within 2 weeks, healing is achieved with a subsequent 2-week use of the drug.

Patients with a duodenal ulcer who are not very susceptible to treatment are usually prescribed omeprazole 40 mg (2 capsules) once a day; ulcer healing usually occurs within 4 weeks. To prevent relapses, patients with duodenal ulcer are recommended omeprazole 20 mg once a day. If necessary, the dose can be increased to 40 mg (2 capsules) once a day.

Stomach ulcer

The recommended dose of omeprazole is 20 mg once a day. The drug provides rapid elimination of symptoms. In most patients, recovery occurs within 4 weeks. In cases where healing does not occur after the first course of taking the drug, a repeated 4-week course is usually prescribed, during which healing is achieved.

Patients with a low-response stomach ulcer are usually prescribed omeprazole 40 mg (2 capsules) once a day; healing is usually achieved within 8 weeks. To prevent relapses, a dose of 20 mg once a day is recommended for patients with stomach ulcers. If necessary, the dose can be increased to 40 mg once a day.

NSAIDs associated with gastric ulcers or duodenal erosions

In the presence of NSAID-associated gastric, duodenal ulcers or gastroduodenal erosions in patients with discontinued or ongoing NSAID therapy, the recommended dose of omeprazole is 20 mg 1 time per day.

The drug provides rapid elimination of symptoms, in most patients the cure occurs within 4 weeks. In those patients who did not recover during the initial therapy period, healing is usually achieved with repeated 4-week use of the drug.

For duodenal ulcers, erosions, and symptoms of dyspepsia associated with NSAIDs, the recommended dose is 20 mg once a day.

Eradication regimens of helicobacter PYLORI in peptic ulcer disease

Three-component treatment regimen:

* omeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg 2 times a day in the morning and evening for 7 days;

* omeprazole 20 mg + metronidazole 400 mg (or tinidazole 500 mg) + clarithromycin 250 mg 2 times a day in the morning and evening for 7 days;

* omeprazole 40 mg (2 capsules) once a day + amoxicillin 500 mg 3 times a day + metronidazole 400 mg 3 times a day for 7 days.

Two-component treatment regimen:

* omeprazole 40-80 mg (2-4 capsules) + amoxicillin 1.5 g daily (the dose should be divided into parts) for 2 weeks.

To ensure complete healing, further treatment should be carried out in accordance with the recommendations in the sections “Duodenal ulcer” and “Gastric ulcer”.

In cases where the test for Helicobacter Pylori remains positive after the course of treatment, the course of treatment can be repeated.

Reflux esophagitis

The recommended dose of omeprazole is 20 mg once a day. The drug provides rapid elimination of symptoms, in most patients the cure occurs within 4 weeks. In cases where a complete cure does not occur after the first course of taking the drug, a repeated 4-week course of treatment is usually prescribed, during which a cure is achieved.

For patients with severe reflux esophagitis, omeprazole 40 mg (2 capsules) is recommended once a day; treatment usually occurs within 8 weeks.

Patients with reflux esophagitis in remission are prescribed omeprazole 20 mg once a day in the form of long-term courses of maintenance therapy. If necessary, the dose can be increased to 40 mg.

Symptomatic gastro-esophageal reflux disease

The recommended dose of omeprazole is 20 mg once a day. The drug provides rapid elimination of symptoms. If after 4 weeks of treatment (20 mg once a day) the symptoms do not disappear, an additional examination of the patient is recommended.

Dyspepsia associated with high acidity

To relieve pain and/or eliminate discomfort in the epigastric region, with or without heartburn, omeprazole is prescribed 20 mg 1 time a day. If after 4 weeks of treatment the symptoms do not disappear, an additional examination of the patient is recommended.

Zollinger-Ellison syndrome

Patients with Zollinger-Ellison syndrome are prescribed the drug in an individual dosage. Treatment is continued according to clinical indications for as long as necessary. The recommended starting dose is 60 mg (3 capsules) daily.

In all patients with a severe form of the disease, as well as in cases where other therapeutic methods did not lead to the desired result, the use of the drug was effective in more than 90% of patients with a daily intake of 20-120 mg of the drug. In cases where the daily dose of the drug exceeds 80 mg (4 capsules), the dose should be divided into two parts and take 2 capsules 2 times a day.

Impaired renal function

No dose adjustment is required in patients with impaired renal function.

Impaired liver function

In patients with hepatic impairment, the bioavailability and plasma half-life of omeprazole are increased. In this regard, a dose of 20 mg per day is sufficient.

Elderly patients (aged > 65 years)

No dose adjustment is required in the elderly. Children

Gastroesophageal reflux disease (GERD) in children over 2 years of age (body weight more than 20 kg).

20 mg once a day. If necessary, the dose can be increased to 40 mg (2 capsules) once a day. The duration of treatment for reflux esophagitis is 4-8 weeks. The duration of treatment for symptomatic treatment of heartburn and acid belching in GERD is 2-4 weeks. If the use of omeprazole for 2-4 weeks does not resolve the symptoms of the disease, further examination is recommended.

Helicobacter Pylori-associated duodenal ulcer (as part of combination therapy) in children over 4 years of age (body weight more than 31 kg).

In order to eliminate Helicobacter pylori in children over 4 years of age with duodenal ulcer, combination therapy is carried out taking into account national and regional recommendations for bacterial resistance (using appropriate antibacterial agents). Omeprazolna is prescribed 20 mg 2 times a day. The duration of treatment is 7-14 days.

Overdose

Single oral doses of omeprazole up to 400 mg (20 capsules) they did not cause any severe symptoms. Single doses of omeprazole 560 mg when taken by adults caused symptoms of moderate intoxication. When the dose was increased, the rate of drug elimination did not change, and no specific treatment was required.

Symptoms: dizziness, confusion, apathy, headache, vascular dilatation, nausea, vomiting, tachycardia, flatulence, diarrhea.

Treatment: symptomatic, if necessary gastric lavage, use of activated charcoal.

Special instructions

In the presence of any alarming symptoms (for example, such as significant spontaneous weight loss, repeated vomiting, dysphagia, vomiting with blood or melena), as well as in the presence of a stomach ulcer (or if a stomach ulcer is suspected), the presence of a malignant neoplasm should be excluded, since treatment with omeprazole, masking the symptoms, may delay the correct diagnosis.

Concomitant use of omeprazole with medications such as atazanavir and nelfinavir is not recommended.

The results of the trials showed a pharmacokinetic/pharmacodynamic interaction between clopidogrel (loading dose of 300 mg and a maintenance dose of 75 mg/day) and omeprazole (80 mg/day orally), which leads to a decrease in exposure to the active metabolite of clopidogrel by an average of 46% and a decrease of the maximal inhibition of ADP-induced platelet aggregation on average 16%.

Therefore, the concomitant use of omeprazole and clopidogrel should be avoided (see section “Interaction with other medicinal products”).

Individual observational studies indicate that proton pump inhibitor therapy may slightly increase the risk of osteoporosis-related fractures, but other similar studies have not shown an increased risk.

In randomized, double-blind, controlled clinical trials of omeprazole and esomeprazole, including two open-label trials with a treatment duration of more than 12 years, the association of osteoporotic fractures with proton pump inhibitors was not confirmed.

Although a causal relationship between omeprazole/esomeprazole use and osteoporotic fractures has not been established, patients at risk of developing osteoporosis or fractures associated with it should be under appropriate clinical supervision.

Due to a decrease in the secretion of hydrochloric acid, the concentration of chromogranin A (DdA) increases. An increase in the concentration of DdA may affect the results of examinations for the detection of neuroendocrine tumors. To prevent this effect, it is necessary to temporarily stop taking omeprazole 5 days before the study of the concentration of DdA.

Influence on the ability to drive vehicles and mechanisms

There are no data on the effect of the drug on the ability to drive a car or other mechanisms. However, due to the fact that dizziness, blurred vision and drowsiness may occur during therapy, care should be taken when driving vehicles or when working with mechanisms that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Capsules

Storage conditions

Store in a dry place, protected from light, at a temperature not exceeding 25 °C

Shelf life

3 years

Active ingredient

Omeprazole

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

Pregnant women as prescribed by a doctor, Nursing mothers as prescribed by a doctor, For adults, Children as prescribed by a doctor, For adults as prescribed by a doctor

Indications

Gastrointestinal infections caused by Helicobacter Pylori, Heartburn, Gastric and Duodenal Ulcers, Reflux Esophagitis