Losek MAPS - instructions for use, dose, side effects, contraindications

Excipients: cellulose microcrystalline 170.0 mg, glyceryl monostearate (40-55) 1.1 mg, giprolose 3.5 mg, hypromellose 10.0 mg, magnesium stearate 0.5 mg, methacrylic and ethacrylic acid copolymer 23.0 mg, paraffin 0 , 1 mg, macrogol 1.9 mg, polysorbate (80) 0.1 mg, crospovidone 3.5 mg, sodium stearyl fumarate 0.3 mg, sucrose spherical pellets 22.0 mg, talc 6.1 mg, titanium dioxide (E171 ) 1.8 mg, triethyl citrate 6.8 mg, iron dye red oxide (E172) 0.04 mg, iron dye oxide yellow (E172) 0.02 mg.

tablets 20 mg:

Active substance: Omeprazole magnesium 20.6 mg (equivalent to 20 mg of omeprazole). Excipients: cellulose microcrystalline 220.0 mg, glyceryl monostearate (40-55) 1.4 mg, giprolose 4.8 mg, hypromellose 15.0 mg, magnesium stearate 0.7 mg, methacrylic and ethacrylic acid copolymer 27.0 mg, paraffin 0 , 2 mg, macrogol 2.5 mg, polysorbate (80) 0.1 mg, crospovidone 4.6 mg, sodium stearyl fumarate 0.5 mg, sucrose spherical granules 22.0 mg, talc 8.3 mg, titanium dioxide (E171 ) 2.2 mg, triethyl citrate 8.2 mg, iron dye red oxide (E172) 0.3 mg.

Description:

tablets 10 mg: oblong biconvex tablet of light pink color, covered with a film membrane, with engraving 10 mG on one side and the icon on the other side.

tablets 20 mg: oblong biconvex tablet pink, covered with a film membrane, with engraving 20 mG on one side and, the icon on the other side.

Pharmacotherapeutic group:glands of the stomach secretion-lowering agent - proton pump inhibitor

ATX: & nbsp

A.02.B.C.01 Omeprazole

Pharmacodynamics:

Mechanism of action

Omeprazole is a weak base. Concentrates in acidic environment of secretory tubules of parietal

cells of the gastric mucosa, is activated and inhibits the proton pump - the enzyme H⁺, K⁺-ATPase. Effect of omeprazole on the last stage of the process of formation of hydrochloric acid in the stomach is dose-dependent and provides a highly effective inhibition of basal and stimulated secretion of hydrochloric acid regardless of the stimulating factor.

Effect on secretion of gastric juice Losek® MAPS® with daily oral administration provides rapid 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, Losek® MAPS® 20 mg causes a steady decrease in 24-hour gastric acidity by at least 80%. At the same time, the average maximum concentration of hydrochloric acid is reduced after pentagastrin stimulation by 70% within 24 hours.

In patients with duodenal ulcer Losek® MAPS® 20 mg with daily oral administration maintains an acidity value in the intragastric pH> 3 on average for 17 hours per day. The inhibition of the secretion of hydrochloric acid depends on the area under the curve

concentration-time (AUC) omeprazole, and not on the concentration of the drug in the plasma at a given time.

Action on Helicobacter pylori Omeprazole has a bactericidal effect on Helicobacter pylori in vitro. Eradication Helicobacter pylori when omeprazole is used together with antibacterial agents it is accompanied by a rapid elimination of symptoms, a high degree of healing of defects in the gastrointestinal mucosa and a prolonged remission of peptic ulcer, which reduces the likelihood of complications such as bleeding, as effectively as constant maintenance therapy.

Other effects associated with inhibition of hydrochloric acid secretion In patients taking drugs that reduce the secretion of the glands of the stomach, for a long period of time, the formation of glandular cysts in the stomach is more often noted; cysts are benign and pass independently on the background of continuation of therapy. These phenomena are caused by physiological changes due to inhibition of hydrochloric acid secretion.

Decrease in secretion of hydrochloric acid in the stomach under the influence of proton pump inhibitors or other gastric acid-lowering agents, leads to an increase in the growth of normal microflora

intestines, which in turn can 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, probably also a bacterium Clostridium difficile.

During treatment with drugs that reduce the secretion of the glands of the stomach, 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). Increase in concentration CgA can influence the results of examinations for the detection of neuroendocrine tumors.To prevent this effect, therapy with proton pump inhibitors should be stopped 5 to 14 days before the study concentration CgA. If during this time the concentration CgA did not return to the normal value, the study should be repeated.

In children and adult patients who took long-term omeprazole, there was an increase in the number of enterochromaffin-like cells, probably due to an increase in the concentration of gastrin in the blood serum. Clinical significance of this phenomenon is not.

Pharmacokinetics:

Distribution

Omeprazole is absorbed in the small intestine, usually for 3-6 hours. Bioavailability after ingestion is approximately 60%. Eating does not affect the bioavailability of omeprazole.

The binding index of omeprazole with 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, CYP2C19 and CYP3A4. The resulting metabolites - sulfone, sulfide and hydroxy-omeprazole - do not significantly affect the secretion of hydrochloric acid.

General information plasma clearance is 0.3-0.6 l / min. Bioavailability of omeprazole

increases by approximately 50% with repeated admission as compared with a single dose.

Excretion

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

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:

Losek® MAPS® is intended for treatment the following diseases:

- duodenal ulcer

- gastric ulcer

- NSAID associated ulcers and erosion of the stomach and duodenum

- eradication Helicobacter pylori with peptic ulcer

- reflux esophagitis

- symptomatic gastroesophageal reflux disease

- dyspepsia associated with increased acidity

Zollinger-Ellison syndrome

Contraindications:

Known hypersensitivity to omeprazole, substituted benzimidazoles or other ingredients in the formulation.

Deficiency sucrose / isomaltase,

intolerance to fructose, glucose galactose malabsorption.

Carefully:

If there are symptoms such as significant spontaneous weight loss, frequent vomiting, dysphagia, vomiting with blood or melena, and if there is a stomach ulcer (or suspected gastric ulcer), the presence of a malignant tumor should be excluded, since treatment can lead to masking of symptoms and , thus delaying the diagnosis.

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 applied in therapeutic doses, exposure to the baby is unlikely.

Dosing and Administration:

Inside. Tablets Losek® MAPS® is recommended in the morning, the tablet should be swallowed whole, washed down with liquid. Tablets can not be chewed or crushed.

Tablets can be dissolved in water or slightly acidified liquid, for example, in fruit juice. The resulting solution should be used within 30 minutes.To be sure of taking the full dose, pour the liquid back into the glass halfway, shake and drink.

Duodenal ulcer. Patients with an active duodenal ulcer are recommended to take Losek MAPS® 20 mg once a day. The drug provides a rapid elimination of symptoms. In most patients, healing of the ulcer occurs in

within 2 weeks. In those cases when complete healing of the ulcer does not occur within 2 weeks, the healing is achieved with a subsequent 2-week treatment with Losek® MAPS®.

Patients with an ulcer of the duodenum, little susceptible to treatment, are usually prescribed Losek® MAPS® 40 mg once a day; healing of the ulcer usually occurs within 4 weeks.

To prevent relapse, patients with duodenal ulcers are recommended Losek® MAPS® 10 mg once a day. If necessary, the dose can be increased to 20-40 mg once a day.

Stomach ulcer.

The recommended dose is Losek® MAPS® 20 mg once a day. The drug provides a rapid elimination of symptoms. In most patients, the cure comes within 4 weeks. In those cases when after the first course of taking the drug complete healing does not occur, usually a repeated 4-week course of treatment, during which healing is achieved.

Patients with a stomach ulcer that is less susceptible to treatment are usually prescribed Losek® MAPS® 40 mg once daily; healing is usually achieved within 8 weeks.

To prevent relapse, patients with stomach ulcers are recommended Losek® MAPS® 20 mg once daily. When

the necessary dose can be increased to 40 mg once a day.

NSAID associated ulcers and erosion of the stomach and duodenum In the presence of NSAIDs associated gastric ulcers, duodenal ulcers or gastroduodenal erosions in patients with discontinued or continuing therapy with NSAIDs, the recommended dose of Losek® MAPS® is 20 mg once daily. The drug provides a rapid elimination of symptoms, in most patients, cure occurs within 4 weeks. In those patients who have not had a cure during the initial therapy period, healing is usually achieved with a repeated 4-week treatment.

For the prevention of ulcers and erosions of the stomach and duodenum and symptoms of dyspepsia associated with the administration of NSAIDs, a dose of Losek® MAPS® 20 mg once daily is recommended.

Modes of eradication Helicobacter pylori (Hp) with peptic ulcer. Three-component treatment regimen:

Losek® MAPS® 20 mg, amoxicillin 1 g and clarithromycin 500 mg. All medications should be taken 2 times a day for one week or

Losek® MAPS® 20 mg, metronidazole 400 mg (or tinidazole 500 mg) and clarithromycin 250 mg. All drugs are taken 2 times in

day for one week or

Losek® MAPS® 40 mg once a day, and also amoxicillin 500 mg and metronidazole 400 mg 3 times a day for one week.

Two-component treatment regimen:

Losek® MAPS® 40-80 mg daily and amoxicillin 1.5 g daily (dose should be divided into parts) within two weeks. During clinical trials, amoxicillin in a daily dose of 1.5-3 g, Losek® MAPS® 40 mg once a day and clarithromycin 500 mg 3 times a day for two weeks.

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

In those cases when, after taking a course of treatment, a test for Helicobacter pylori remains positive, the course of treatment can be repeated.

Reflux esophagitis.

The recommended dose is one Losek® MAPS® 20 mg tablet once a day. The drug provides a rapid elimination of symptoms.In most patients, the cure comes within 4 weeks. In those cases when, after the first course of taking the drug, there is no complete cure, usually a second 4-

week course of treatment, during which a cure is achieved.

Patients with severe form of esophagitis reflux are recommended Losek® MAPS® 40 mg once a day; Cure usually occurs within 8 weeks.

Patients with reflux-esophagitis in the remission phase are prescribed Losek MAPS® 10 mg once a day in the form of long courses of maintenance therapy. If necessary, the dose can be increased to 20-40 mg.

Symptomatic gastro-oesophageal reflux disease.

The recommended dose is Losek® MAPS® 20 mg once a day. The drug provides a rapid elimination of symptoms. The therapeutic effect can be achieved with a daily dose of 10 mg, so individual dose selection is not excluded. If after 4 weeks of treatment (Losek® MAPS® 20 mg once a day) the symptoms do not disappear, an additional examination of the patient is recommended.

Dyspepsia associated with increased acidity.

To alleviate pain and / or eliminate discomfort in the epigastric region, with heartburn or without heartburn, Losek® MAPS® 20 mg once a day is prescribed.The therapeutic effect can be achieved at a dose of 10 mg 1 time per day, so treatment can begin with this dose. If after 4 weeks of treatment (Losek®

MAPS® 20 mg once a day) the symptoms do not disappear, an additional examination of the patient is recommended.

Zollinger-Ellison syndrome.

Patients with Zollinger-Ellison syndrome are given the drug in an individual dosage. Treatment is continued according to clinical indications as long as necessary. The recommended initial dose is Losek® MAPS® 60 mg daily. In all patients with severe disease, and also when other therapeutic methods did not lead to the desired result, the use of the drug was effective in more than 90% of patients receiving 20-120 mg of Losek® MAPS® daily. In those cases when 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.

For patients with impaired renal function, dose adjustment is not required. Violation of the function of the liver.

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

Patients of advanced age.

For elderly patients, dose adjustment is not required.Experience with children is limited

Side effects:

SIDE EFFECTS

The following side effects are independent of the omeprazole dosing regimen that were noted during clinical trials, as well as in post-marketing applications.

Often

(>1/100,

<1/10)

Headache, abdominal pain, diarrhea, flatulence, nausea / vomiting, constipation

Infrequently

(>1/1000,

<1/100)

Dermatitis, itching, rash, hives, drowsiness, insomnia, dizziness, paresthesia, malaise, increased activity of "liver" enzymes

Rarely

(>1/10000,

<1/1000)

Reactions

hypersensitivity (eg, fever, angioedema, anaphylactic reaction / anaphylactic

	shock, bronchospasm, hepatitis (with or without jaundice), liver failure, encephalopathy in patients with liver disease, arthralgia, myalgia, muscle weakness, leukopenia, thrombocytopenia, agranulocytosis, pancytopenia, depression, hyponatremia, agitation, aggression, confusion, hallucinations, impaired taste, blurred vision, dry mouth, stomatitis,candidiasis of the gastrointestinal tract, alopecia, photosensitivity, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, interstitial nephritis, gynecomastia, sweating, peripheral edema, microscopic colitis
Highly rarely (<1/10000)	Hypomagnesemia, hypocalcemia due to severe hypomagnesemia, hypokalemia due to hypomagnesemia

There have been reports of cases of the formation of glandular cysts in the stomach in patients,

taking drugs that reduce the secretion of the glands of the stomach, for a long period of time; cysts are benign and pass independently on the background of continuation of therapy.

Overdose:

Single oral doses of Losek® MAPS® to 400 mg did not cause any severe symptoms. Adults with 560 mg of omeprazole showed moderate intoxication. With increasing dose, the elimination rate of the drug did not change (first-order kinetics), but no specific treatment was required.

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

Treatment: symptomatic treatment, if necessary, gastric lavage, the appointment of activated charcoal.

Interaction:Effect of omeprazole on pharmacokinetics

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

Like other drugs that reduce the acidity of gastric juice, treatment with omeprazole may lead to a decrease in absorption of ketoconazole, itraconazole and erlotinib, as well as an increase in the absorption of drugs such as digoxin. Joint reception of omeprazole at a dose of 20 mg once a day and digoxin increases the bioavailability of digoxin by 10% (bioavailability of digoxin was increased by up to 30% in 20% of patients).

It was shown that omeprazole interacts with some antiretroviral drugs. The mechanisms and the clinical significance of these interactions are not always known. An increase in pH on the background of omeprazole therapy may affect the absorption of antiretroviral drugs. It is also possible to interact at the isoenzyme level CYP2C19. When combined use of omeprazole and some antiretroviral drugs, such as atazanavir and nelfinavir, against the background of therapy with omeprazole there is a decrease in their concentration in serum. Concerning

joint use of omeprazole with antiretroviral drugs, such as atazanavir and nelfinavir, Not recommended.

With the simultaneous use of omeprazole and saquinavir, an increase in the concentration of saquinavir in the serum was noted, while with use with some other antiretroviral drugs their concentration did not change.

Omeprazole inhibits CYP2C19 the main isoenzyme involved in its metabolism. Joint use of omeprazole with other drugs, in the metabolism of which isoenzyme participates CYP2C19, such as diazepam, warfarin (R-warfarin) or other antagonists of vitamin K, phenytoin and cilostazol, can lead to a slowdown in the metabolism of these drugs. It is recommended that patients who receive phenytoin and omeprazole, it may be necessary to reduce the dose of phenytoin. However, the concomitant treatment with omeprazole at a daily dose of 20 mg does not affect the concentration of phenytoin in the plasmablood in patients who take the drug for a long time. When using omeprazole by patients receiving warfarin or other antagonists of vitamin K, monitoring of the international normalized relationship is necessary; in some cases, you may need to reduce the dose of warfarin or another antagonist

vitamin K. 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 long-term warfarin.

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

The pharmacokinetic / pharmacodynamic interaction between clopidogrel (loading dose 300 mg and maintenance dose 75 mg / day) and omeprazole (80 mg / day inwards), which leads to a decrease in exposure to the active metabolite of clopidogrel, was observed on the 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.An increased risk of cardiovascular complications with the combined use of clopidogrel and proton pump inhibitors, including omeprazole, has not been shown in a prospective, randomized, unfinished study involving more than 3,760 patients receiving placebo or omeprazole in a dose of 20 mg / day. simultaneously with clopidogrel therapy and

acetylsalicylic acid (ASA), and has not been confirmed by an additional non-randomized analysis of the clinical outcomes of large-scale, prospective, randomized trials involving more than 47,000 patients.

The results of several observational studies are contradictory and do not give an unambiguous answer about the presence or absence of an increased risk of thromboembolic cardiovascular complications against the background of joint use of clopidogrel and proton pump inhibitors.

When clopidogrel was used together with a fixed combination of 20 mg of esomeprazole and 81 mg of ASA, the exposure to the active metabolite of clopidogrel decreased by almost 40% compared to clopidogrel alone, with the maximum levels of inhibition of ADP-induced platelet aggregation being the same,is associated with the simultaneous administration of ASA in a low dose.

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

There was no interaction of omeprazole with the following drugs: caffeine, theophylline, S-warfarin, piroxicam,

diclofenac, naproxen, metoprolol, propranolol and ethanol.

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

Some patients reported increased concentrations of methotrexate against a background of combined use with proton pump inhibitors. When appointing high doses of methotrexate, consideration should be given to the possibility of a temporary omeprazole withdrawal.

The effect of drugs on the pharmacokinetics of omeprazole In the metabolism of omeprazole, isozymes participate CYP2C19 and CYP3A4.

The combined use of omeprazole and isozyme inhibitors CYP2C19 and CYP3A4, such as clarithromycin and voriconazole, can lead to an increase in the concentration of omeprazole in the blood plasma by slowing the metabolism omeprazole. A joint

The use of voriconazole and omeprazole results in more than twice

increase AUC omeprazole. Due to the good tolerability of high doses of omeprazole, at short

joint application of

drugs are not requires dose adjustment

omeprazole.

Medicines that induce isoenzymes CYP2C19 and CYP3A4, such

as rifampicin and preparations of St. John's wort perfumed, when combined with omeprazole may lead to a decrease in the concentration of omeprazole in the blood plasma due to the acceleration of the metabolism of omeprazole.

Special instructions:

In the presence of any anxiety symptoms (for example, such as significant spontaneous weight loss, repeated vomiting, dysphagia, vomiting with a trace of blood or melena), and if there is a stomach ulcer (or suspected gastric ulcer), the presence of a malignant tumor treatment with Losek® MAPS® can lead to a smoothing of the symptoms and delay the diagnosis.

It is not recommended to use omeprazole together with such drugs as atazanavir and nelfinavir.

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

simultaneous application of omeprazole and clopidogrel (see section "Interaction with other drugs and other forms of interaction").

Separate 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 trials with a duration of therapy of more than 12 years, the connection of fractures against osteoporosis with proton pump inhibitors was not confirmed.

Although the causal relationship between the use of omeprazole / esomeprazole with fractures against osteoporosis is not established, patients with a risk of developing osteoporosis or fractures against it should be under appropriate clinical supervision.

Effect on the ability to drive transp. cf. and fur:

There is no evidence of the effect of Losek® MAPS® on the ability to drive a car or other mechanisms. However, due to the fact that during therapy there may be dizziness, blurred vision and drowsiness, care should be taken when driving vehicles or other mechanisms.

Form release / dosage:

Tablets, film-coated 10 mg or 20 mg.

Packaging:

For tablets 10 mg:

For 14 tablets in a plastic bottle with a screwed plastic lid with the control of the first opening. Each bottle is packed in a cardboard box with

instructions for use.

For tablets 20 mg:

For 14 or 28 tablets in a plastic bottle with a screwed plastic lid with the control of the first opening. Each bottle is packed in a cardboard box with instructions for use.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

After use, cover the bottle tightly closed. Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N013848 / 01

Date of registration:29.09.2011

The owner of the registration certificate:AstraZeneca ABAstraZeneca AB Sweden

Manufacturer: & nbsp

ASTRAZENECA, AB Sweden

Representation: & nbspAstraZeneca Pharmaceuticals Ltd.AstraZeneca Pharmaceuticals Ltd.

Information update date: & nbsp24.02.2014

Illustrated instructions

Instructions

Losek® MAPS® (Losec® MUPS®)