Losec Mups, pills 20mg, 28pcs

Composition

One 20 mg film-coated tablet contains: Active ingredient:  omeprazole magnesium 20.6 mg (equivalent to 20.0 mg of omeprazole). Auxiliary substances:  glyceryl monostearate 40-55 1,4 mg hyprolose 4,8 mg 15,0 mg hypromellose, magnesium stearate 0.7 mg, and metacrilato methacrylic acid copolymer 27,0 mg, microcrystalline cellulose 220,0 mg,0.2 mg paraffin, macrogol 2.5 mg, Polysorbate 80 0.1 mg, crospovidone 4,6 mg, sodium fumarate 0.5 mg, sucrose, spherical granules size 0,250-0,355 22.0 mg, talc 8.3 mg, titanium dioxide (E 171) 2.2 mg, triethylcitrate 8.2 mg, dye iron oxide red E 172 0.3 mg.

Pharmacological action

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

Losek ® MAPS® with daily oral use provides rapid and effective inhibition of day and night hydrochloric acid secretion. The maximum effect is achieved within 4 days of treatment.

In patients with duodenal ulcer, Losek ® MAPS® 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 ulcer, Losek ® MAPS® 20 mg with daily oral use maintains an intragastric acidity value of pH ≥ 3, on average, 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 plasma at a given time.

Action on Helicobacter pylori

Omeprazole has a bactericidal effect on Helicobacter pylori in vitro. 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

In patients taking drugs that reduce the secretion of gastric glands for a long period of time, the formation of glandular cysts in the stomach is more often noted; the cysts are benign and 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 agents that reduce gastric acidity 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 Salmonella spp. and Campylobacter spp., and in hospitalized patients, probably also by 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 (CgA) increases. Increasing the concentration of CgA may affect the results of examinations for the detection of neuroendocrine tumors (see the section “Special instructions”).

To prevent this effect, therapy with proton pump inhibitors should be suspended at least 5 days before the CgA concentration study. If CgA and gastrin concentrations have not returned to normal during this time, the study should be repeated 14 days after discontinuation of omeprazole.

In children and adult patients who took omeprazole for a long time, an increase in the number of enterochromaffin-like cells was noted, probably due to 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. Bioavailability after oral use is approximately 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

Omeprazole is completely metabolized in the liver. The main enzymes involved in the metabolic process are SUR2C19 and SUR3A4. The resulting metabolites-sulfone, sulfide, and hydroxy-omeprazole-do not significantly affect the secretion of hydrochloric acid.

The total plasma clearance is 0.3-0.6 l/min. The bioavailability of omeprazole increases by approximately 50% with repeated use compared to a single dose.

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 by 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
• eradication of Helicobacter pylori in peptic ulcer disease (in combination with appropriate antibacterial therapy)
• reflux esophagitis
• symptomatic gastro-esophageal reflux disease
• dyspepsia associated with high acidity
• Zollinger-Ellison syndrome

Children and adolescents Children over 2 years of age with a body weight of at least 20 kg:

• reflux esophagitis
• symptomatic gastro-esophageal reflux disease

Children over 4 years of age and teenagers:

• Duodenal ulcer caused by Helicobacter pylori

Use during pregnancy and lactation

The results of the studies showed no side effects of omeprazole on the health of pregnant women, on the fetus or on the newborn. Losek ® MAPS® can be used during pregnancy. Omeprazole penetrates into breast milk, but when used in therapeutic doses, the effect on the child is unlikely.

Contraindications

• Known hypersensitivity to omeprazole, substituted benzimidazoles, or other ingredients that make up the drug.
• Sucrose/isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption.
• Concomitant use with erlotinib, posaconazole.
• Children under 2 years of age.
• Children over 2 years of age for other indications, except for the treatment of reflux esophagitis and symptomatic gastroesophageal reflux disease.
• Children over 4 years of age for other indications, except for the treatment of esophagitis reflux, symptomatic gastroesophageal reflux disease and duodenal ulcer caused by Helicobacter pylori.

Use caution in patients with osteoporosis. In the presence of symptoms such as 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), the presence of malignancy should be excluded, since treatment may mask the symptoms and thus delay the diagnosis.

Side effects

Nervous system and sensory disorders:  headache, dizziness, paresthesia, insomnia or drowsiness, vertigo; in some cases — confusion, agitation, depression, hallucinations (in predisposed patients), encephalopathy on the background of severe liver disease.

From the digestive tract:  diarrhea or constipation, abdominal pain, nausea, vomiting, flatulence; rarely-increased activity of liver enzymes; in some cases-dry mouth, stomatitis, gastrointestinal candidiasis, liver dysfunction, hepatitis with or without jaundice.

From the side of the skin:  rarely-rash, pruritus; in some cases — photosensitization, erythema multiforme, alopecia.

From the musculoskeletal system:  in some cases — arthralgia, myalgia, muscle weakness.

Cardiovascular and blood disorders (hematopoiesis, hemostasis):  leukopenia, thrombocytopenia, agranulocytosis, pancytopenia.

Allergic reactions:  rarely-urticaria; in some cases-angioedema, fever, bronchospasm, interstitial nephritis, anaphylactic shock.

Other services:  malaise; rarely-impaired vision, taste sensations; in some cases-increased sweating, edema, gynecomastia, hyponatremia.

Interaction

Effect of omeprazole on the pharmacokinetics of other medicinal productsreduction of hydrochloric acid secretion 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.

Similar to other drugs that reduce the acidity of gastric juice, treatment with omeprazole may reduce the absorption of ketoconazole, itraconazole, posaconazole and erlotinib, as well as increase the absorption of drugs such as digoxin.

Couse of omeprazole at a dose of 20 mg once a day and digoxin increases the bioavailability of digoxin by 10% (digoxin bioavailability increased by up to 30% in 20% of patients). Concomitant use of Losek ® MAPS® with erlotinib or posaconazole is contraindicated (see section “Contraindications”).

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; when used with some other antiretroviral drugs, their concentration did not change.

Omeprazole inhibits SUR2C19, 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 cilostazol, 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 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.

A pharmacokinetic/pharmacodynamic interaction was observed between clopidogrel (loading dose 300 mg and maintenance dose 75 mg/day) and omeprazole (80 mg/day). oral use), which leads to a decrease in exposure to the active metabolite of clopidogrel, on average, by 46% and a decrease in the maximum inhibition of ADP-induced platelet aggregation, on average, by 16%.

The clinical significance of this interaction is not clear.

The increased risk of cardiovascular events associated with the co-use of clopidogrel and proton pump inhibitors, including omeprazole, was not shown in a prospective randomized incomplete study involving more than 3,760 patients receiving placebo or omeprazole at a dose of 20 mg/day simultaneously with clopidogrel and acetylsalicylic acid (ASA), and was not confirmed by an additional non-randomized analysis of the clinical outcomes of large-scale prospective studies. randomized trials involving more than 47,000 patients.

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.

When clopidogrel was co-administered with a fixed combination of 20 mg esomeprazole and 81 mg ASA, exposure to the active metabolite of clopidogrel decreased by almost 40% compared to clopidogrel monotherapy, while the maximum levels of inhibition of ADP-induced platelet aggregation were the same, which is probably due to the simultaneous use of ASA at a low dose.

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

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

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 was noted against the background of co-use with proton pump inhibitors. When prescribing high doses of methotrexate, the possibility of temporarily stopping the use of omeprazole should be considered.

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 and voriconazole, can lead to an increase in the concentration of omeprazole in blood plasma due to slowing down the metabolism of omeprazole.

The combined use of voriconazole and omeprazole 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.

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

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 the concentration of omeprazole in blood plasma due to the acceleration of omeprazole metabolism.

How to take, course of use and dosage

Inside, in the morning, the tablet should be swallowed whole, without chewing, washed down with liquid (you can dissolve the tablet in water or slightly acidified liquid, for example in fruit juice; the resulting solution should be used within 30 minutes).

Duodenal ulcer disease: in the acute phase-20 mg 1 time a day daily for 2 weeks; if there is no effect for 2 weeks, a second 2 – week course is prescribed.

In case of duodenal ulcer resistant to therapy-40 mg once a day for 4 weeks. For the prevention of relapses of duodenal ulcer — 10 mg (if necessary — up to 20-40 mg/day) 1 time a day.

Gastric ulcer: 20 mg once a day daily for 4 weeks; in the absence of an effect, a repeated 4-week course. For peptic ulcer disease resistant to therapy-40 mg once a day for 8 weeks. To prevent relapses of gastric ulcer — 20 mg (if necessary — up to 40 mg) 1 time a day.

NSAID-associated gastric ulcers or duodenal erosions: 20 mg once daily for 4 weeks. If there is no effect, a repeated 4-week course of treatment is prescribed.

Modes of eradication of Helicobacter pylori in gastric ulcer disease.

Three-component treatment regimen:

Losec Mups 20 mg, amoxicillin 1 g and clarithromycin 500 mg (all drugs are taken 2 times a day for 1 week) or Losec Mups 20 mg, metronidazole 400 mg (or tinidazole 500 mg) and clarithromycin 250 mg (all drugs are taken 2 times a day for 1 week), or Losec Mups 40 mg 1 time a day, amoxicillin 500 mg and metronidazole 400 mg 3 times a day for 1 week.

Two-component treatment regimen: Losec Mups 40-80 mg and amoxicillin 1.5 g daily (the dose should be divided into parts) for 2 weeks. Losec Mups 40 mg once daily, amoxicillin 1.5–3 g daily, and clarithromycin 500 mg 3 times daily for 2 weeks were used in clinical trials. If the Helicobacter pylori test remains positive after treatment, the course can be repeated.

Reflux esophagitis: 20 mg once a day for 4 weeks. If there is no effect, repeat the 4-week course. Patients with severe reflux esophagitis — 40 mg once a day for 8 weeks. For reflux esophagitis in remission — 10 mg once a day (if necessary-up to 20-40 mg / day) for a long time.

Symptomatic gastro-esophageal reflux disease, dyspepsia associated with increased production of hydrochloric acid: 10-20 mg / day daily for 4 weeks. If the symptoms do not disappear at the end of therapy, an additional examination of the patient is recommended.

Zollinger-Ellison syndrome: the dosage regimen is set individually. The recommended starting dose is 60 mg / day. 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 taking 20-120 mg of Losec Mups daily.

If the daily dose exceeds 80 mg, it should be divided into 2 hours and taken 2 times a day.

In elderly patients, as well as in patients with impaired renal function, no dose adjustment is required.

With impaired liver function, the bioavailability of omeprazole and T1/2 from plasma increases, and therefore a dose of 10-20 mg is sufficient.

Overdose

Single oral doses of Losek ® MAPS® up to 400 mg did not cause any severe symptoms. Moderate intoxication was observed when adults received 560 mg of omeprazole. When the dose was increased, the rate of drug elimination did not change (first-order kinetics), and no specific treatment was required. Symptoms: dizziness, confusion, apathy, headache, vascular dilatation, tachycardia, nausea, vomiting, flatulence, diarrhea. Treatment: symptomatic

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 Losek® MAPS® may smooth out the symptoms and delay the diagnosis. Concomitant use of omeprazole with medications such as atazanavir and nelfinavir is not recommended.

A pharmacokinetic/pharmacodynamic interaction was observed between clopidogrel (loading dose 300 mg and maintenance dose 75 mg/day) and omeprazole (80 mg/day). oral use), 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 concomitant use of omeprazole and clopidogrel should be avoided (see section “Interactions with other drugs and other forms of interaction”).

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.

Increasing the concentration of CgA may affect the results of examinations for the detection of neuroendocrine tumors (see the section “Pharmacodynamics”).

To prevent this effect, therapy with proton pump inhibitors should be suspended at least 5 days before the CgA concentration study. If CgA and gastrin concentrations have not returned to normal during this time, the study should be repeated 14 days after discontinuation of omeprazole.

Effects on the ability to drive vehicles, mechanisms There are no data on the effect of Losek® MAPS® on the ability to drive vehicles and mechanisms. However, due to the fact that dizziness, blurred vision and drowsiness may occur during therapy, care should be taken when driving vehicles and mechanisms.

Storage conditions

Store at a temperature not exceeding 25°C. After application, close the bottle cap tightly. Keep out of reach of children.

Shelf

life is 3 years. Do not use after the expiration date indicated on the package.

Active ingredient

Omeprazole

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

Nursing mothers as prescribed by a doctor, Adults as prescribed by a doctor, Pregnant Women as prescribed by a doctor

Indications

Reflux esophagitis, Gastric and duodenal ulcers, Gastrointestinal infections caused by Helicobacter pylori