Losek MAPS, 20 mg 28 pcs.

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, it activates and inhibits the proton pump – H+,K+-ATPase enzyme. 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

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

In patients with duodenal ulcer Losec® MAPS® 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 of 70% within 24 hours.

In patients with duodenal ulcer Losec® MAPS® 20 mg with daily oral administration maintains intragastric acidity at pH ≥ 3 for an average of 17 hours per day.

The 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 pylori

Omeprazole has a bactericidal effect on Helicobacter pylori in vitro. Eradication of Helicobacter pylori when using omeprazole in combination with antibacterial agents is accompanied by rapid elimination of symptoms, a high degree of healing of gastrointestinal mucosal defects and long-term remission of peptic ulcer disease, which reduces the likelihood of complications such as bleeding as effectively as continuous maintenance 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 glandular cysts in the stomach; the cysts are benign and go away on their own with continued therapy. These phenomena are caused by physiological changes resulting from inhibition of hydrochloric acid secretion.

The reduction of gastric hydrochloric acid secretion by proton pump inhibitors or other gastric acid reducing agents leads to increased growth of normal gut microflora, which in turn may lead to a slightly increased risk of gut infections caused by Salmonella spp. and Campylobacter spp. bacteria, and probably also by Clostridium difficile in hospitalized patients.

When treated with drugs that decrease gastric gland secretion, serum gastrin concentrations increase. Due to decreased secretion of hydrochloric acid, the concentration of chromogranin A (CgA) increases. Increased concentration of CgA may affect the results of examinations to detect neuroendocrine tumors (see section “Special indications”).

In order to prevent this effect, proton pump inhibitor therapy should be suspended for at least 5 days before CgA testing. 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 pediatric and adult patients on long-term omeprazole an increase in enterochromaffin-like cells has been observed, probably related to 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. Bioavailability after oral administration is approximately 60%. Food intake has no effect on 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 fully metabolized in the liver. The main enzymes involved in the process of metabolism are SUR2C19 and SUR3A4. The resulting metabolites – sulfone, sulfide and hydroxy-omeprazole have no significant effect on hydrochloric acid secretion.

The total plasma clearance is 0.3-0.6 l/min. Bioavailability of omeprazole is increased by approximately 50% when repeated administration 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 by the intestine.

Particular patient groups

There are no significant changes in bioavailability of omeprazole 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

Active ingredient

Composition

How to take, the dosage

In the morning, the tablet should be swallowed whole, without chewing, with liquid (the tablet can be dissolved in water or slightly acidic liquid, such as fruit juice; the resulting solution should be used within 30 minutes).

Duodenal ulcer: in acute phase – 20 mg 1 time per day daily for 2 weeks; in case of no effect within 2 weeks a repeated 2-week course is prescribed.

In case of duodenal ulcer resistant to therapy – 40 mg 1 time per day for 4 weeks. For prevention of recurrence of duodenal ulcer – 10 mg (if necessary – up to 20-40 mg/day) once daily.

Peptic ulcer of the stomach: 20 mg 1 time daily for 4 weeks; in the absence of effect – repeated 4-week course. With gastric ulcer resistant to therapy – 40 mg 1 time per day for 8 weeks. For prevention of gastric ulcer recurrence – 20 mg (if necessary, up to 40 mg) once daily.

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 peptic ulcer disease.

The three-component treatment regimen:

. Losek MAPS 20 mg, amoxicillin 1 g, and clarithromycin 500 mg (all drugs taken 2 times daily for 1 week) or Losek MAPS 20 mg, metronidazole 400 mg (or tinidazole 500 mg) and clarithromycin 250 mg (all drugs taken 2 times daily for 1 week), or Losek MAPS 40 mg once daily, amoxicillin 500 mg and metronidazole 400 mg 3 times daily for 1 week.

The two-component treatment regimen: Losek MAPS 40-80 mg and amoxicillin 1.5 g daily (dose should be divided into parts) for 2 weeks. During clinical trials, Losek MAPS 40 mg once daily, amoxicillin 1.5-3 g daily, and clarithromycin 500 mg 3 times daily for 2 weeks were used. If the Helicobacter pylori test remains positive after treatment, the course may be repeated.

Reflux esophagitis: 20 mg once daily for 4 weeks. If there is no effect, repeat 4 week course. In patients with severe form of reflux esophagitis – 40 mg 1 time per day for 8 weeks. In 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 at the end of the therapy the symptoms do not disappear, additional examination of the patient is recommended.

Zollinger-Ellison syndrome: dosage regimen is determined individually. The recommended starting dose is 60 mg/day. In all patients with severe disease and also in cases when other therapeutic methods did not lead to the desired result, the use of the drug was effective in more than 90% of patients while taking 20-120 mg of Losek MAPS daily.

If the daily dose exceeds 80 mg, it should be divided by 2 h. and taken twice daily.

In elderly patients and in patients with impaired renal function, no dose adjustment is necessary.

The bioavailability and T1/2 of omeprazole from plasma are increased in patients with hepatic impairment, therefore a dose of 10-20 mg is adequate.

Interaction

Like other drugs that reduce gastric acidity, treatment with omeprazole may decrease absorption of ketoconazole, itraconazole, posaconazole and erlotinib, and increase absorption of drugs such as digoxin.

The co-administration of omeprazole in dose of 20 mg once daily and digoxin increases digoxin bioavailability by 10% (digoxin bioavailability was increased by up to 30% in 20% of patients). Concomitant administration 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 pH during therapy with omeprazole may affect the absorption of antiretrovirals. There may also be an interaction at the level of CYP2C19 isoenzyme.

When omeprazole and some antiretroviral drugs such as atazanavir and nelfinavir are used together during therapy with omeprazole, a decrease in their serum concentrations is noted. In this regard, co-administration of omeprazole with antiretrovirals such as atazanavir and nelfinavir is not recommended.

In concomitant use of omeprazole and saquinavir an increase in serum concentrations of saquinavir was noted, when used with some other antiretrovirals their concentrations were not changed.

Omeprazole inhibits SUR2C19, the main isoenzyme involved in its metabolism. Co-administration of omeprazole with other drugs whose metabolism involves the CYP2C19 isoenzyme, such as diazepam, warfarin (R-warfarin) or other vitamin K antagonists, phenytoin and cilostazol may lead to slower metabolism of these drugs. Monitoring of patients taking phenytoin and omeprazole is recommended; a reduction in the dose of phenytoin may be required.

However, concomitant treatment with omeprazole at a daily dose of 20 mg has no effect on plasma concentrations of phenytoin in patients taking the drug for a long time. When using omeprazole in patients receiving warfarin or other vitamin K antagonists, international normalized ratio monitoring is necessary; in some cases, it may be necessary to reduce the dose of warfarin or other vitamin K antagonist.

In contrast, concomitant treatment with omeprazole at a daily dose of 20 mg does not alter the coagulation time in patients on long-term warfarin.

The use of omeprazole in a dose of 40 mg once daily led to 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.

An interaction between clopidogrel (loading dose of 300 mg and maintenance dose of 75 mg/day) and omeprazole (80 mg/day) was observed pharmacokinetic/pharmacodynamic in studies. orally), which results in decreased exposure to the active metabolite clopidogrel, on average, by 46% and decreased maximal inhibition of ADP-induced platelet aggregation, on average, by 16%.

The clinical significance of this interaction is unclear.

An increased risk of cardiovascular complications with clopidogrel and proton pump inhibitors, including omeprazole, has not been shown in a prospective randomized, incomplete study involving more than 3,760 patients receiving placebo or omeprazole at a dose of 20 mg/day. concomitantly with clopidogrel and acetylsalicylic acid (ASA) therapy, and was not confirmed by additional non-randomized analyses of clinical outcomes from large-scale prospective randomized trials involving more than 47,000 patients.

The results of several observational studies are inconsistent and do not provide a definitive answer about the presence or absence of an increased risk of thromboembolic cardiovascular complications with clopidogrel and proton pump inhibitors.

When clopidogrel was coadministered with a fixed combination of 20 mg of esomeprazole and 81 mg of ASA, exposure to the active metabolite clopidogrel was reduced by nearly 40% compared with clopidogrel monotherapy, while maximum levels of inhibition of ADP-induced platelet aggregation were similar, which is likely due to the simultaneous administration of low-dose ASA.

Omeprazole does not affect the metabolism of drugs metabolized by the SUR3A4 isoenzyme, such as cyclosporine, lidocaine, quinidine, estradiol, erythromycin and budesonide.

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

In concomitant use of omeprazole and tacrolimus, increased serum concentrations of tacrolimus have been noted.

In some patients, a slight increase in methotrexate concentrations with proton pump inhibitors has been noted. If high doses of methotrexate are prescribed, temporary discontinuation of omeprazole should be considered.

The effect of drugs on pharmacokinetics of omeprazole

The CYP2C19 and CYP3A4 isoenzymes are involved in metabolism of omeprazole. Concomitant use of omeprazole and inhibitors of CYP2C19 and CYP3A4 isoenzymes, such as clarithromycin and voriconazole, may lead to increased plasma concentrations of omeprazole due to delayed metabolism of omeprazole.

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

The co-administration of omeprazole with amoxicillin or metronidazole does not affect plasma concentrations of omeprazole.

Drugs that induce CYP2C19 and CYP3A4 isoenzymes, such as rifampicin and preparations of St. John’s wort, when used together with omeprazole may lead to decreased plasma concentration of omeprazole due to accelerated metabolism of omeprazole.

Special Instructions

According to the results of studies, a pharmacokinetic/pharmacodynamic interaction between clopidogrel (loading dose of 300 mg and maintenance dose of 75 mg/day) and omeprazole (80 mg/day orally) was noted, resulting in an average 46% decrease in exposure to the active metabolite clopidogrel and an average 16% decrease in maximum inhibition of ADP-induced platelet aggregation.

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

Some observational studies suggest that therapy with proton pump inhibitors may slightly increase the risk of osteoporosis-related fractures, but other such studies have not shown an increased risk.

In randomized, double-blind, controlled clinical trials of omeprazole and esomeprazole, including two open-label studies with more than 12 years of therapy, the association of osteoporosis-related fractures with proton pump inhibitors has not been confirmed.

While a causal relationship between omeprazole/esomeprazole use and osteoporotic fractures has not been established, patients at risk for osteoporosis or osteoporotic fractures should receive appropriate clinical monitoring.

Elevated CgA concentrations may affect the results of neuroendocrine tumor screenings (see section “Pharmacodynamics”).

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

Contraindications

Side effects

Nervous system and sense organs: headache, dizziness, paresthesia, insomnia or somnolence, vertigo; in some cases – confusion, agitation, depression, hallucinations (in predisposed patients), encephalopathy against severe liver disease.

Gastrointestinal system disorders: diarrhea or constipation, abdominal pain, nausea, vomiting, flatulence; rarely – increased liver enzymes activity; in some cases – dry mouth, stomatitis, gastrointestinal candidiasis, liver dysfunction, hepatitis with or without jaundice.

Skin disorders: rash and itching are rare; in isolated cases photosensitization, erythema multiforme, alopecia.

Musculoskeletal system: in some cases – arthralgia, myalgia, muscle weakness.

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

Allergic reactions: rare – urticaria; in some cases – Quincke’s edema, fever, bronchospasm, interstitial nephritis, anaphylactic shock.

Others: malaise; rarely – disorders of vision, taste, in some cases – increased sweating, edema, gynecomastia, hyponatremia.

Overdose

Pregnancy use

Similarities