Gastrozole, 20 mg capsules 28 pcs

Pharmacotherapeutic group: gastric gland secretion reducing agent – proton pump inhibitor

ATX code: A02BC01

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 and activates and inhibits proton pump enzyme H⁺, K⁺ – ATPase. The effect of omeprazole on the last stage of the process of hydrochloric acid formation in the stomach is dose-dependent and provides highly effective inhibition of basal and stimulated hydrochloric acid secretion regardless of the stimulating factor.

Impact on gastric juice secretion

Omeprazole with daily oral administration provides rapid and effective inhibition of daytime and nighttime hydrochloric acid secretion.

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

In patients with duodenal ulcer, daily administration of 20 mg of omeprazole maintains intragastric acidity (pH) at ≥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 plasma concentration of the drug at a given time.

Action on Helicobacter pyloriinvitro

Omeprazole has a bactericidal effect on Helicobacter pyloriinvitro.

Eradication of Helicobacter influenza when using omeprazole with antibacterial agents is associated with rapid resolution of symptoms, a high degree of healing of gastrointestinal mucosal defects and prolonged remission of peptic ulcer disease, which reduces the likelihood of complications such as bleeding as effectively as ongoing supportive therapy.

Other effects associated with inhibition of hydrochloric acid secretion

Patients who take drugs that reduce gastric gland secretion over a long period of time are more likely to have benign gastric cysts that go away on their own with continued therapy. These phenomena are caused by physiological changes as a result of inhibition of hydrochloric acid secretion.

The reduction of gastric hydrochloric acid secretion by proton pump inhibitors or other acid-inhibiting agents leads to an increase of normal gut flora, which in turn may slightly increase the risk of intestinal infections caused by Salmonellaspp. and Campylobacterspp. bacteria, and in hospitalized patients probably also by Clostridium difficile.

At the time of treatment with drugs that decrease gastric gland secretion, serum gastrin concentrations increase. Due to the decrease in hydrochloric acid secretion, the concentration of chromogranin A (CgA) increases.

In children and adult patients on long-term omeprazole, there was an increase in enterochromaffin-like cells, probably related to an increase in serum gastrin concentration. This phenomenon has no clinical significance.

Pharmacokinetics

Distribution

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

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

Metabolism

It is almost completely metabolized in the liver. The main enzymes involved in the process of metabolism are CYP2C19 and CYP2A4. The resulting metabolites -sulfone and sulfide have no significant effect on hydrochloric acid secretion. It is an inhibitor of 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 through the intestine.

Special patient groups

No significant changes in bioavailability of omeprazole have been noted in elderly patients or in patients with impaired renal function. In patients with impaired liver function, there is an increase in bioavailability of omeprazole and a significant decrease in plasma clearance.

Indications

Adults

– duodenal ulcer

– stomach ulcer

– NSAID-associated ulcers and erosions of the stomach and duodenum – eradication of Helicobacter pylori in peptic ulcers

– reflux esophagitis

– symptomatic gastroesophageal reflux disease (GERD)

– dyspepsia associated with high acidity

– Zollinger-Ellison syndrome

Children

– gastroesophageal reflux disease in children over 2 years of age

– duodenal ulcer associated with Helicobacter pylori (as part of combination therapy) in children over 4 years of age.

Pharmacological effect

Pharmacotherapeutic group: agent that reduces the secretion of gastric glands – proton pump inhibitor

ATX code: A02BC01

Pharmacological properties

Pharmacodynamics

Mechanism of action

Omeprazole is a weak base. Concentrated in the acidic environment of the secretory tubules of the parietal cells of the gastric mucosa, it 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 secretion of hydrochloric acid, regardless of the stimulating factor.

Effect on gastric juice secretion

Omeprazole, when administered daily orally, provides rapid and effective inhibition of daytime and nighttime hydrochloric acid secretion.

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

In patients with duodenal ulcers, daily administration of 20 mg omeprazole maintains intragastric acidity (pH) at ≥ 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 plasma concentration of the drug at a given time.

Effect on Helicobacter pylori

Omeprazole has a bactericidal effect on Helicobacter pylori in vitro.

Eradication of Helicobacter pylori when using omeprazole in conjunction with antibacterial agents is accompanied by rapid elimination of symptoms, a high degree of healing of defects in the mucous membrane of the gastrointestinal tract and long-term remission of peptic ulcer disease, which reduces the likelihood of complications such as bleeding, as effectively 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 experience the formation of benign gastric cysts that go away on their own with continued therapy. These phenomena are caused by physiological changes resulting from inhibition of hydrochloric acid secretion.

Reducing the secretion of hydrochloric acid in the stomach under the influence of proton pump inhibitors or other acid-inhibiting agents leads to an increase in the growth of normal intestinal microflora, which in turn may lead to a slight increase in the risk of developing intestinal infections caused by bacteria of the genus Salmonella spp. and Campylobacter spp., and in hospitalized patients also probably Clostridium difficile.

During treatment with drugs that reduce 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 (CgA) increases.

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

Pharmacokinetics

Distribution

Omeprazole is absorbed in the small intestine, usually within 3–6 hours, the time to reach maximum concentration (Tcmax) is 0.5–3.5 hours. Bioavailability after a single oral dose is approximately 30–40%; after continuous administration once a day, 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

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 have a significant effect on the secretion of hydrochloric acid. It is an inhibitor of the CYP2C19 isoenzyme.

Excretion

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

Special instructions

If any alarming symptoms are present (eg, significant spontaneous weight loss, repeated vomiting, dysphagia, vomiting blood or melena), or if a gastric ulcer is present (or if a gastric ulcer is suspected), the presence of a malignant neoplasm should be excluded, because Treatment with omeprazole, masking symptoms, may delay the correct diagnosis.

The combined use of omeprazole with drugs such as atazanavir and nelfinavir is not recommended.

According to the results of the studies, a pharmacokinetic/pharmacodynamic interaction was noted between clopidogrel (loading dose of 300 mg and 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 in the maximum inhibition of ADP-induced platelet aggregation by an average of 16%.

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

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

Randomized, double-blind, controlled clinical trials of omeprazole and esomeprazole, including two open-label studies with treatment durations of more than 12 years, did not confirm the association of osteoporotic fractures with the use of proton pump inhibitors.

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

Due to a decrease in the secretion of hydrochloric acid, the concentration of chromogranin A (CgA) increases. Increased concentrations of CgA may affect the results of examinations to detect neuroendocrine tumors. To prevent this effect, it is necessary to temporarily stop taking omeprazole 5 days before the CgA concentration test.

Impact on the ability to drive vehicles and machinery

There is no data on the effect of the drug on the ability to drive a car or use other machinery. However, due to the fact that dizziness, blurred vision and drowsiness may occur during therapy, caution should be exercised when driving or operating machinery that requires increased concentration and speed of psychomotor reactions.

Active ingredient

Omeprazole

Composition

Omeprazole – 235.0 mg (in the form of pellets containing: 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 disubstituted) – 2.9845 mg, calcium carbonate – 7.99 mg, lactose monohydrate – 7.99 mg, hypromellose (hydroxypropyl methylcellulose) – 20.5625 mg, methacrylic acid and ethyl acrylate copolymer [1:1] – 58.75 mg, propylene glycol – 1.9035 mg, diethyl phthalate – 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)

Hard gelatin capsules – 63.0
mg: body: titanium dioxide (E 171) – 2.0000%, gelatin – up to 100%; cap:
titanium dioxide (E171) – 2.0000%, red iron oxide dye (E 172) –
0.7286%, gelatin – up to 100%.

Pregnancy

Pregnancy

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

Breast-feeding

Omeprazole passes into breast milk; the use of omeprazole during breastfeeding is contraindicated.

Contraindications

Hypersensitivity to omeprazole, substituted benzimidazoles or other ingredients included in the drug;

deficiency of lactase, sucrase/isomaltase, lactose intolerance, fructose intolerance, glucose-galactose and malabsorption;

combined use with erlotinib, posaconazole, clarithromycin (in patients with liver failure), St. John’s wort;

breastfeeding period;

children under 18 years of age, with the exception of:

– gastroesophageal reflux disease

– children up to 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 gastric ulcer (or suspected gastric ulcer), pregnancy. The presence of malignancy should be excluded as treatment may mask symptoms and thus delay diagnosis.

Side Effects

The following are side effects, independent of the dosage regimen of omeprazole, that were noted during clinical studies, as well as during post-marketing use. The following adverse events noted with the use of omeprazole are distributed according to the frequency of occurrence in accordance with the following gradation: very often (> 1/10), often (> 1/100 to 1/1000 to 1/10000 to <1/1000), very rarely (< 1/10000), unspecified frequency (cannot be calculated from the available data).

From the digestive system: often – diarrhea, constipation, abdominal pain, nausea, vomiting, flatulence; rarely – dry mouth, stomatitis, gastrointestinal candidiasis, 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 disease.

From the hematopoietic organs: rarely – leukopenia, thrombocytopenia, agranulocytosis, pancytopenia, hypochromic microcytic anemia in children.

From the nervous system: often – headache; uncommon – vertigo, paresthesia, drowsiness; rarely – taste disturbance.

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

From the skin and subcutaneous tissues: infrequently – dermatitis, rash, itching, urticaria; rarely – alopecia, photosensitivity, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

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

Metabolism and nutrition: rarely – hyponatremia; very rarely – hypocalcemia due to severe hypomagnesemia, hypokalemia due to hypomagnesemia; unspecified frequency – hypomagnesemia.

From the mental side: infrequently – insomnia; rarely – agitation, aggression, confusion, hallucinations, depression.

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

From the respiratory system, chest and mediastinal organs: rarely – bronchospasm.

From the kidneys and urinary tract: rarely – interstitial nephritis.

From the genital organs and breast: rarely – gynecomastia.

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

Cases of glandular cysts have been reported
in the stomach in patients taking drugs that reduce gland secretion
stomach, for a long period of time; pass independently on
against the background of continued therapy.

Interaction

The effect of omeprazole on the pharmacokinetics of other drugs. A decrease in the secretion of hydrochloric acid in the stomach during treatment with omeprazole and other proton pump inhibitors can lead to a decrease or increase in the absorption of other drugs, the absorption of which depends on the acidity of the environment.

As with other drugs that suppress the secretion of hydrochloric acid or antacids, treatment with omeprazole may lead to decreased absorption of erlotinib, ketoconazole or itraconazole, as well as increased absorption of digoxin. With simultaneous use of omeprazole (at a dose of 20 mg per day) and digoxin, the bioavailability of digoxin increases by 10%.

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 pH 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 certain antiretroviral drugs, such as atazanavir and nelfinavir, a decrease in their serum concentrations is observed during omeprazole therapy. In this regard, the combined use of omeprazole with antiretroviral drugs such as atazanavir and nelfinavir is not recommended.

With the simultaneous use of omeprazole and saquinavir, an increase in the concentration of saquinavir in serum was noted; 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 metabolized by the CYP2C19 isoenzyme, such as diazepam, warfarin (R-warfarin) or other vitamin K antagonists, phenytoin and cilostozol, may lead to a slower metabolism of these drugs.

Monitoring of patients taking phenytoin and omeprazole is recommended; a dose reduction of phenytoin may be required. However, concomitant treatment with omeprazole at a daily dose of 20 mg does not affect the concentration of phenytoin in the 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 lead to a change in coagulation time in patients taking warfarin for a long time.

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

According to the results of the studies, a pharmacokinetic/pharmacodynamic interaction was noted between clopidogrel (loading dose of 300 mg and 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 in the maximum inhibition of ADP-induced platelet aggregation by an average of 16%.

The clinical significance of this interaction is unclear. An increased risk of cardiovascular complications with concomitant 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 a clear answer about the presence or absence of an increased risk of thromboembolic cardiovascular complications during 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.

There was no interaction of omeprazole with the following drugs: antacids, theophylline, caffeine, propranolol, ethanol, S-warfarin, piroxicam, diclofenac, naproxen, metoprolol.

With the simultaneous use of omeprazole and tacrolimus, an increase in the concentration of tacrolimus in the blood serum was noted.

In some patients, a slight increase in plasma concentrations of methotrexate has been reported when administered concomitantly with proton pump inhibitors. When using high doses of methotrexate, you should temporarily stop taking omeprazole.

Effect of drugs 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 lead to increased plasma concentrations of omeprazole by slowing down the metabolism of omeprazole.

Concomitant use of omeprazole and voriconazole results in a more than twofold increase in the AUC of omeprazole. Due to the good tolerance of high doses of omeprazole, short-term joint use of these drugs does not require dose adjustment of omeprazole.

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

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

Overdose

Single oral doses of omeprazole up to 400 mg (20 capsules) did not cause any severe symptoms. Single doses of omeprazole 560 mg when taken by adults caused symptoms of moderate intoxication. As 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, administration of activated carbon.

Storage conditions

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

Shelf life

3 years

Manufacturer

Pharmstandard-Leksredstva, Russia