Losek Maps tablets p / o 20mg, No. 28

LosecЃ MAPSЃ is intended for the treatment of the following diseases:

• duodenal ulcer; stomach ulcer;

• NSAIDs associated ulcers and erosion of the stomach and duodenum;

• eradication of Helicobacter pylori in peptic ulcer disease;

• reflux esophagitis;

• symptomatic gastroesophageal reflux disease;

• dyspepsia associated with high acidity;

• Zollinger-Ellison syndrome.

Inside. It is recommended to take LosecЃ MAPSЃ tablets in the morning, the tablet should be swallowed whole with some liquid. Tablets should not be chewed or crushed.

The tablets can be dissolved in water or in a slightly acidic liquid such as fruit juice. The resulting solution should be used within 30 minutes. To be sure you are taking the full dose, pour half the liquid into the glass again, shake and drink.

Duodenal ulcer

Patients with active duodenal ulcer are recommended to take LosecЃ MAPSЃ 20 mg 1 time per day. The drug provides quick relief of symptoms. In most patients, ulcer healing occurs within 2 weeks. In those cases when complete healing of the ulcer does not occur within 2 weeks, healing is achieved with a subsequent 2-week administration of LosecЃ MAPSЃ.

Patients with duodenal ulcer, not very responsive to treatment, are usually prescribed LosecЃ MAPSЃ 40 mg 1 time per day; the ulcer usually heals within 4 weeks.

To prevent relapses, patients with duodenal ulcer are recommended LosecЃ MAPSЃ 10 mg 1 time per day. If necessary, the dose can be increased to 20-40 mg once a day.

Stomach ulcer

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

LosecЃ MAPSЃ 40 mg 1 time per day is usually prescribed to patients with gastric ulcers, little susceptible to treatment; healing is usually achieved within 8 weeks.

To prevent relapses, patients with stomach ulcers are recommended to use LosecЃ MAPSЃ 20 mg once a day. If necessary, the dose can be increased to 40 mg once a day.

NSAIDs associated ulcers and erosion of the stomach and duodenum

In the presence of NSAIDs associated stomach ulcers, duodenal ulcers or gastroduodenal erosions in patients with discontinued or ongoing NSAID therapy, the recommended dose of LosecЃ MAPSЃ is 20 mg once a day. The drug provides rapid elimination of symptoms, in most patients, cure occurs within 4 weeks. In those patients who did not heal during the period of initial therapy, healing is usually achieved with repeated 4 weeks of taking the drug.

For the prevention of ulcers and erosions of the stomach and duodenum and symptoms of dyspepsia associated with taking NSAIDs, the recommended dose of LosecЃ MAPSЃ is 20 mg once a day.

Modes of eradication of Helicobacter pylori in peptic ulcer disease.

Three-component treatment regimen:

LosecЃ MAPSЃ 20 mg, amoxicillin 1 g and clarithromycin 500 mg. All drugs are taken 2 times a day for one week.

or

LosecЃ MAPSЃ 20 mg, metronidazole 400 mg (or tinidazole 500 mg) and clarithromycin 250 mg. All drugs are taken 2 times a day for one week.

or

LosecЃ MAPSЃ 40 mg once a day, as well as amoxicillin 500 mg and metronidazole 400 mg 3 times a day for one week.

Two-component treatment regimen:

LosecЃ MAPSЃ 40-80 mg daily and amoxicillin 1.5 g daily (the dose should be divided into parts) for two weeks. During clinical trials, amoxicillin was used in a daily dose of 1.5-3 g, LosecЃ MAPSЃ 40 mg once a day and clarithromycin 500 mg three times a day for two weeks.

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

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

Reflux esophagitis

The recommended dose is one LosecЃ MAPSЃ 20 mg tablet once a day. The drug provides quick relief of symptoms. For most patients, cure occurs within 4 weeks. In cases where, after the first course of taking the drug, a complete cure does not occur, a repeated 4-week course of treatment is usually prescribed, during which a cure is achieved.

For patients with severe reflux esophagitis, LosecЃ MAPSЃ 40 mg 1 time per day is recommended; healing usually occurs within 8 weeks.

Patients with reflux esophagitis in remission are prescribed LosecЃ MAPSЃ 10 mg 1 time per day in the form of long courses of maintenance therapy. If necessary, the dose can be increased to 20-40 mg.

Symptomatic gastroesophageal reflux disease.

The recommended dose is LosecЃ MAPSЃ 20 mg once a day. The drug provides quick relief of symptoms. The therapeutic effect can be achieved with a daily dose of 10 mg, therefore, individual dose selection is not excluded. If after 4 weeks of treatment (LosecЃ MAPSЃ 20 mg 1 time per day) symptoms do not disappear, additional examination of the patient is recommended.

Acid-related dyspepsia

To relieve pain and / or eliminate feelings of discomfort in the epigastric region, with or without heartburn, LosecЃ MAPSЃ 20 mg is prescribed once a day. The therapeutic effect can be achieved at a dose of 10 mg 1 time per day, so treatment can be started with this dose. If after 4 weeks of treatment (LosecЃ MAPSЃ 20 mg 1 time per day) symptoms do not disappear, additional examination of the patient is recommended.

Zollinger-Ellison Syndrome

For patients with Zollinger-Ellison syndrome, the drug is prescribed in an individual dosage. Treatment is continued according to clinical indications as long as necessary. The recommended starting dose is LosecЃ MAPSЃ 60 mg 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 drug was effective in more than 90% of patients when taking 20-120 mg of LosecЃ MAPSЃ daily. In cases where the daily dose of the drug exceeds 80 mg, the dose should be divided into two parts and taken 2 times a day.

Impaired renal function

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

Liver dysfunction

In patients with impaired liver function, the bioavailability and plasma half-life of omeprazole are increased. In this regard, a dose of 10-20 mg per day is sufficient.

Elderly patients

No dose adjustment is required for elderly patients.

Children

Experience with children is limited.

Film-coated tablets

1 tab.

omeprazole

Excipients : microcrystalline cellulose, glyceryl monostearate (40-55), hyprolose, hypromellose, magnesium stearate, copolymer of methacrylic and ethacrylic acids, paraffin, macrogol, polysorbate 80, crospovidone, sodium stearyl fumarate, sucrose spherical granules17 , triethyl citrate, iron oxide red dye (E172).

• known hypersensitivity to omeprazole, substituted benzimidazoles or other ingredients in the drug.

Carefully

If symptoms such as significant spontaneous weight loss, frequent vomiting, dysphagia, vomiting of blood or melena are present, or if a stomach ulcer is present (or if a stomach ulcer is suspected), malignancy should be ruled out as treatment may mask symptoms and thus delay the diagnosis.

pharmachologic effect

Mechanism of action

Omeprazole is a weak base. Concentrates in the acidic environment of the secretory tubules of parietal cells of the gastric mucosa, activates 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 acid secretion

LosecЃ MAPSЃ with daily oral administration provides fast and effective inhibition of day and night secretion of hydrochloric acid. The maximum effect is achieved within 4 days of treatment. In patients with duodenal ulcer, LosecЃ MAPSЃ 20 mg causes a sustained 24-hour decrease in gastric acidity by at least 80%. This achieves a decrease in the average maximum concentration of hydrochloric acid after stimulation with pentagastrin by 70% within 24 hours.

In patients with duodenal ulcer, LosecЃ MAPSЃ 20 mg with daily oral administration maintains the acidity value in the intragastric medium at a pH level> 3 on average for 17 hours a day.

The 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. The eradication of Helicobacter pylori when omeprazole is used together with antibacterial agents is accompanied by rapid elimination of symptoms, a high degree of healing of defects in the gastrointestinal mucosa and prolonged 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

In patients taking drugs that lower the secretion of gastric glands, for a long period of time, the formation of glandular cysts in the stomach is more often observed; cysts are benign and go away on their own while continuing therapy. These phenomena are due to physiological changes as a result of inhibition of the secretion of hydrochloric acid.

A decrease in the secretion of hydrochloric acid in the stomach under the action of proton pump inhibitors or other drugs that reduce the acidity of the stomach 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 probably also Clostridium difficile in hospitalized patients.

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. An increase in CgA concentration may affect the results of examinations for the detection of neuroendocrine tumors. To prevent this effect, therapy with proton pump inhibitors must be suspended 5-14 days before the study of the CgA concentration. If during this time the concentration of CgA has not returned to the normal value, the study should be repeated.

In children and adult patients taking omeprazole for a long time, there was an increase in the number of enterochromaffin-like cells, 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. Bioavailability after oral administration is approximately 60%. Food intake does not affect the bioavailability of omeprazole.

The index of binding 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 CYP2C19 and CYP3A4. 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 is increased by approximately 50% with repeated administration compared to taking a single dose.

Withdrawal

T1 / 2 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.

Application during pregnancy and lactation

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

Omeprazole passes into breast milk, however, when used in therapeutic doses, it is unlikely to affect the child.

Application for violations of liver function

In patients with impaired liver function, the bioavailability and plasma half-life of omeprazole are increased. In this regard, a dose of 10-20 mg per day is sufficient.

Application for impaired renal function

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

Application in children

Experience with children is limited.

Use in elderly patients

No dose adjustment is required for elderly patients.

special instructions

If you have any alarming symptoms (for example, such as significant spontaneous weight loss, repeated vomiting, dysphagia, vomiting with blood or melena), or if you have a stomach ulcer (or if you suspect a stomach ulcer), you should exclude the presence of a malignant neoplasm, because treatment with LosecЃ MAPSЃ can lead to a smoothing of symptoms and delay the diagnosis.

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

According to the results of 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 by mouth), 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.

Some 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 studies with a duration of therapy for more than 12 years, the association of fractures associated with osteoporosis with the use of proton pump inhibitors has not been confirmed.

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

Impact on the ability to drive a car or other mechanisms

There is no data on the effect of LosecЃ MAPSЃ 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, caution should be exercised when driving vehicles or other mechanisms.

Overdose

Single oral doses of LosecЃ MAPSЃ up to 400 mg did not cause any severe symptoms. When adults took 560 mg of omeprazole, moderate intoxication was noted. With an increase in the dose, 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.

Ћечение: симптоматическое лечение, при необходимости - промывание желудка, назначение активированного угл¤.

Ћекарственное взаимодействие

¬ли¤ние омепразола на фармакокинетику других лекарственных препаратов

—нижение секреции сол¤ной кислоты в желудке при лечении омепразолом и другими ингибиторами протонного насоса может привести к снижению или повышению абсорбции других препаратов, всасывание которых зависит от кислотности среды.

ѕодобно другим препаратам, снижающим кислотность желудочного сока, лечение омепразолом может привести к снижению всасывани¤ кетоконазола, итраконазола и эрлотиниба, а так же повышению всасывани¤ таких препаратов, как дигоксин.

—овместный прием омепразола в дозе 20 мг один раз в сутки и дигоксина повышает биодоступность дигоксина на 10%
(биодоступность дигоксина повышалась на величину до 30% у 20% пациентов).

Ѕыло показано, что омепразол взаимодействует с некоторыми антиретровирусными препаратами.

ћеханизмы и клиническое значение этих взаимодействий не всегда известны. ”величение значени¤ рЌ на фоне терапии омепразолом может вли¤ть на всасывание антиретровирусных препаратов. “акже возможно взаимодействие на уровне изофермента CYP2C19. ѕри совместном применении омепразола и некоторых антиретровирусных препаратов, таких как атазанавир и нелфинавир, на фоне терапии омепразолом отмечаетс¤ снижение их концентрации в сыворотке. ¬ св¤зи с этим совместное применение омепразола с антиретровирусными препаратами, такими как атазанавир и нелфинавир, не рекомендуетс¤.

ѕри одновременном применении омепразола и саквинавира было отмечено повышение концентрации саквинавира в сыворотке, при применении с некоторыми другими антиретровирусными препаратами их концентраци¤ не мен¤лась.

ќмепразол ингибирует CYP2C19 - основной изофермент, участвующий в его метаболизме. —овместное применение омепразола с другими препаратами, в метаболизме которых принимает участие изофермент CYP2C19, такими как диазепам, варфарин (R-варфарин) или другие антагонисты витамина  , фенитоин и цилостазол, может привести к замедлению метаболизма этих препаратов. –екомендуетс¤ наблюдение за пациентами, принимающими фенитоин и омепразол, может потребоватьс¤ снижение дозы фенитоина. ќднако сопутствующее лечение омепразолом в суточной дозе 20 мг не вли¤ет на концентрацию фенитоина в плазме крови у пациентов, длительно принимающих препарат. ѕри применении омепразола пациентами, получающими варфарин или другие антагонисты витамина  , необходим мониторинг международного нормализованного отношени¤; в р¤де случаев может понадобитьс¤ снижение дозы варфарина или другого антагониста витамина  . ¬ то же врем¤ сопутствующее лечение омепразолом в суточной дозе 20 мг не приводит к изменению времени коагул¤ции у пациентов, длительно принимающих варфарин.

ѕрименение омепразола в дозе 40 мг один раз в сутки приводило к увеличению Cmax и AUC цилостазола на 18% и 26%, соответственно; дл¤ одного из активных метаболитов цилостазола увеличение составило 29% и 69%, соответственно. ѕо результатам исследований отмечено фармакокинетическое/фармакодинамическое взаимодействие между клопидогрелом (нагрузочна¤ доза 300 мг и поддерживающа¤ доза 75 мг/сут) и омепразолом (80 мг/сут внутрь), которое приводит к снижению экспозиции к активному метаболиту клопидогрела, в среднем, на 46% и снижению максимального ингибировани¤ ј?‘-индуцированной агрегации тромбоцитов, в среднем, на 16%.

 линическа¤ значимость этого взаимодействи¤ не ¤сна. ѕовышение риска сердечно-сосудистых осложнений при совместном применении клопидогрела и ингибиторов протонного насоса, в том числе омепразола, не было показано в проспективном рандомизированном незавершенном исследовании с участием более 3760 пациентов, получавших плацебо или омепразол в дозе 20 мг/сут одновременно с терапией клопидогрелом и ацетилсалициловой кислотой (ј— ), и не подтверждено дополнительным нерандомизированным анализом клинических исходов масштабных проспективных рандомизированных исследований с участием более 47000 пациентов.

–езультаты р¤да наблюдательных исследований противоречивы и не дают однозначного ответа о наличии или отсутствии повышенного риска тромбоэмболических сердечно-сосудистых осложнений на фоне совместного применени¤ клопидогрела и ингибиторов протонного насоса.

ѕри применении клопидогрела совместно с фиксированной комбинацией 20 мг эзомепразола и 81 мг ј—  экспозици¤ к активному метаболиту клопидогрела снизилась почти на 40% по сравнению с монотерапией клопидогрелом, при этом максимальные уровни ингибировани¤ ј?‘-индуцированной агрегации тромбоцитов были одинаковыми, что, веро¤тно, св¤зано с одновременным приемом ј—  в низкой дозе.

ќмепразол не вли¤ет на метаболизм препаратов, метаболизируемых изоферментом CYP3A4, таких как, циклоспорин, лидокаин, хинидин, эстрадиол, эритромицин и будесонид.

Ќе вы¤влено взаимодействи¤ омепразола со следующими препаратами: кофеин, теофиллин, S -варфарин, пироксикам, диклофенак, напроксен, метопролол, пропранолол и этанол.

ѕри одновременном применении омепразола и такролимуса было отмечено повышение концентрации такролимуса в сыворотке крови.

” некоторых пациентов отмечали повышение концентрации метотрексата на фоне совместного применени¤ с ингибиторами протонного насоса. ѕри назначении высоких доз метотрексата следует рассмотреть возможность временной отмены омепразола.

¬ли¤ние лекарственных препаратов на фармакокинетику омепразола

¬ метаболизме омепразола участвуют изоферменты —YP2C19 и —YP3 ј4. —овместное применение омепразола и ингибиторов изоферментоз —YP2C19 и CYP3A4, таких как кларитромицин и вориконазол, может приводить к повышению концентрации омепразола в плазме крови за счет замедлени¤ метаболизма омепразола. —овместное применение вориконазола и омепразола приводит к более чем двукратному увеличению AUC омепразола. ¬ св¤зи с хорошей переносимостью высоких доз омепразола, при непродолжительном совместном применении указанных препаратов не требуетс¤ коррекции дозы омепразола.

Medicines that induce CYP2C19 and CYP3A4 isoenzymes, such as rifampicin and St. John's wort preparations, when used together with omepraeol, can lead to a decrease in the concentration of omeprazole in the blood plasma by accelerating the metabolism of omeprazole.