Neo-Text - instructions for use, dose, side effects, contraindications

Name matter	Content
Name matter	20 mg	40 mg
Active substance:
Esomeprazole magnesium dihydrate (in terms of esomeprazole)	21.7 mg * (20.0 mg)	43.4 mg * (40.0 mg)
Excipients:
Core:
Sugar	16.13 mg	32.26 mg
granules **
Giprolose (Viscosity: from 75 to 150 Pa-s (5%, m / m))	5.94 mg	11.88 mg
Povidone (Viscosity, expressed through the value of k: from 22.50 to 27.00)	5.34 mg	10.68 mg
Talc	6.675 mg	13.35 mg
Titanium dioxide (E 171)	1.335 mg	2.67 mg
Methacrylic acid-ethyl acrylate copolymer (1: 1) dispersion 30%	33.16 mg	66,32
Stearic acid monoglyceride 40-55 Type II	1.985 mg	3.97 mg
Propylene glycol	5.93 mg	11.86 mg
Stearic acid Type 50	4.64 mg	9.28 mg
Polysorbate-80	0.78 mg	1.56 mg
Simethicone	0.045 mg	0.09 mg
Cellulose	240.12 mg	480.24 mg

Microcrystal- The (The particle size is from 50 to 200 μm)
Macrogol-6000	27.595 mg	55.19 mg
Crospovidone Type A	6.9 mg	13.8 mg
Silicon dioxide colloidal	0.69 mg	1.38 mg
Magnesium stearate	0.69 mg	1.38 mg
Sheath:
Gipromellose (Viscosity: from 4.8 to 7.8 Pa-s)	19.455 mg	34.35 mg
Macrogol-6000	4.785 mg	8.45 mg
Titanium dioxide (E 171)	4.245 mg	4.15 mg
Talc	1.44 mg	2.55 mg
The iron dye red oxide (E 172)	0.0563 mg	0.5 mg
Iron colorant oxide yellow (E 172)	0.0188 mg

* The amount of the substance contained in the tablet indicated on the label reflects the stoichiometric ratio of esomeprazole to esomeprazole magnesium dihydrate.

** The size of granules: from 212 to 300 microns.

The composition of the pellets:

Sucrose - from 80 to 91,5%;

Corn starch - from 8.5 to 20%; Dextrose liquid (dextrose, oligo- and polysaccharides) - no more than 5.0%.

Description:

Tablets 20 mg

Light pink oval tablets covered with a film sheath.

On a cross-section: tablets of white or almost white color.

Tablets 40 mg

Pink with a weak brownish tinge and impregnations of a darker color oval tablets, covered with a film shell,with risk from both sides.

On a cross-section: tablets of white or almost white color.

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

ATX: & nbsp

A.02.B.C.05 Esomeprazole

Pharmacodynamics:

Esomeprazole is the S-isomer of omeprazole and reduces the secretion of hydrochloric acid in the stomach by specifically inhibiting the proton pump in parietal cells. Both isomers of omeprazole, S- and R-isomers, have similar pharmacodynamic activity.

Mechanism of action

Esomeprazole is a weak base, accumulates in the secretory tubules of parietal cells in the highly acidic environment of the stomach where the enzyme H + / K + -ATPase is activated and inhibits the proton pump. Esomeprazole inhibits both basal and stimulated secretion of hydrochloric acid.

The effect on acid secretion in stomach

The action of esomeprazole develops within 1 hour after ingestion of 20 mg or 40 mg. With daily intake of the drug for 5 days at a dose of 20 mg once a day, the average maximum concentration of hydrochloric acid after stimulation with pentagastrin is reduced by 90% (when measuring the acid concentration 6-7 hours after taking the drug on the 5th day of therapy).

In patients with gastroesophageal reflux disease (GERD) and the presence of clinical symptoms after 5 days of daily intake of esomeprazole inside at a dose of 20 mg or 40 mg, the pH in the stomach was higher than 4 for an average of 13 and 17 hours in 24 hours. Against the background taking the drug at a dose of 20 mg / day. the intragastric pH above 4 was maintained for 8, 12 and 16 hours in 76%, 54%, and 24% of patients, respectively. For 40 mg of esomeprazole, this ratio is 97%, 92% and 56%, respectively.

A correlation was found between acid secretion and drug concentration in blood plasma (AUC parameter (area under the concentration-time curve) was used to estimate the concentration). Therapeutic effect achieved as a result of inhibition of acid secretion When taking esomeprazole at a dose of 40 mg / day. the treatment of reflux esophagitis occurs in approximately 78% of patients after 4 weeks of therapy and in 93% after 8 weeks of therapy.

Treatment with esomeprazole at a dose of 20 mg 2 times / day. in combination with appropriate antibiotics for one week leads to successful eradication of Helicobacter pylori in approximately 90% of patients.

Patients with uncomplicated peptic ulcer after a weekly eradication course do not need follow-up monotherapy with antisecretory drugs for ulcer healing and symptom management.

Other effects associated with inhibition of acid secretion During treatment with antisecretory drugs, the level of gastrin in the blood plasma increases as a result of decreased acid secretion. Due to a decrease in the secretion of hydrochloric acid, the concentration of chromogranin A (CgA) increases. An increase in CgA concentration may influence the results of the examinations to identify neuroendocrine tumors. To prevent this effect, it is necessary to temporarily stop taking esomeprosol 5 days before the CgA study.

Patients who received long-term esomeprazole, there is an increase in the number of enterochromaffin-like cells, probably associated with an increase in the level of gastrin in the blood plasma.

In patients who used antisecretory drugs for a long time, the formation of glandular cysts in the stomach is more often noted. This phenomenon

is due to physiological changes due to inhibition of acid secretion.

Cysts are benign and undergo reverse development.

The use of drugs that inhibit the secretion of hydrochloric acid in the stomach, including proton pump inhibitors (IPN), is accompanied by

an increase in the content of the microbial flora in the stomach, normally present in the gastrointestinal tract (GIT). The use of IPN can lead to a slight increase in the risk of infectious diseases of the gastrointestinal tract caused by bacteria of the genus Salmonella spp. and Campylobacter spp. and, in hospitalized patients, probably Clostridium difficile.

In two comparative studies with ranitidine esomeprazole showed better efficacy in healing gastric ulcers in patients receiving non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2).

In the course of two studies on the evaluation of effectiveness esomeprazole has shown high efficacy in the prevention of gastric ulcers and CVD in patients (age group over 60 years and / or peptic ulcer in the anamnesis) who received NSAIDs, including selective COX-2 inhibitors.

Pharmacokinetics:

Absorption and distribution

Esomeprazole is unstable in an acidic medium, therefore, for oral administration, tablets are used that include granules with a shell resistant to the action of gastric juice.The conversion of esomeprazole to the 11-isomer under conditions in vivo is insignificant.

Absorption of esomeprazole is fast, the time to reach the maximum plasma concentration (TC_mOh) is 1-2 hours after ingestion. Absolute bioavailability is 64% after a single dose of 40 mg and rises to 89% after repeated administration. For esomeprazole in a dose of 20 mg, the values were 50% and 68%, respectively. The volume of distribution is 0.22 l / kg. The connection with plasma proteins is 97%. Eating slows and reduces absorption of esomeprazole in the stomach, but this does not have a significant effect on the inhibition of hydrochloric acid secretion.

Metabolism and excretion

Esomeprazole is completely metabolized by the cytochrome P450 system (CYP). The bulk of esomeprazole is metabolized by a specific polymorphic isoform CYP2C19, thus forming hydroxy- and demethylated metabolites of esomeprazole. The metabolism of the remainder is carried out by another specific isoform CYP3A4; This produces a sulfo derivative of esomeprazole, which is the main metabolite, determined in plasma.

In patients with active isoenzyme CYP2C19 ("fast" metabolizers) systemic clearance - 17 l / h after a single dose and 9 l / h - after repeated intake. T1/2 - 1.3 hours with systematic admission in the dosing regimen once a day. The area under the concentration-time curve (AUC) increases on the background of multiple reception (nonlinear dose dependence and AUC with systematic admission, which is a consequence of a decrease in metabolism during the "first passage" through the liver, as well as a decrease in systemic clearance caused by inhibition of the isoenzyme CYP2C19 esomeprazole and / or its sulfo-containing metabolite).

With daily intake once a day esomeprazole completely removed from the blood plasma during a break between doses and does not cumulate.

The main metabolites of esomeprazole do not affect the secretion of hydrochloric acid in the stomach. When administered orally, up to 80% of the dose taken is excreted by the kidneys with urine (less than 1% - unchanged), the rest is excreted with feces.

Pharmacokinetics in some patient groups

Approximately 2.9 ± 1.5% of the population has an enzyme CYP2C19 is inactive (patients with inactive metabolism) and metabolism of esomeprazole is carried out mainly by the enzyme CYP3A4.With the systematic administration of 40 mg of esomeprazole once a day, the mean AUC is 100% higher than the value of this parameter in patients with active metabolism (with the participation of the enzyme CYP2C19). Mean values of maximum concentration (C_max) in plasma in patients with inactive metabolism increased by approximately 60%. These features do not affect the dosage and method of use of esomeprazole.

In patients of advanced age (71-80 years), the metabolism of esomeprazole does not undergo significant changes.

After a single dose of 40 mg esomeprazole, the mean AUC in women it is 30% higher than that of men. With daily intake of the drug once a day, there are no differences in pharmacokinetics in men and women.

These features do not affect the dosage and method of use of esomeprazole.

Metabolism of esomeprazole in patients with mild or moderate hepatic insufficiency is similar to that in patients with normal liver function. With severe hepatic insufficiency, the metabolic rate is reduced, which is accompanied by an increase AUC in 2 times, therefore it is recommended to prescribe the maximum daily dose of the drug - 20 mg.The study of pharmacokinetics in patients with renal insufficiency was not carried out. Because the kidneys exclude not the most esomeprazole, but its metabolites, it can be assumed that the metabolism of esomeprazole in patients with renal insufficiency does not change.

In children aged 12-18 years after repeated administration of 20 mg and 40 mg of esomeprazole, the value AUC and time to reach the maximum concentration (TC_max) in the blood plasma was similar to the values AUC and TS_max in adults.

Indications:

Gastroesophageal reflux disease:

- treatment of erosive reflux esophagitis;

- prolonged maintenance treatment after healing of erosive reflux esophagitis to prevent relapse;

- symptomatic treatment of gastroesophageal reflux disease. Stomach ulcer and duodenal ulcer in combination therapy:

- treatment of duodenal ulcers associated with Helicobacter pylori;

- prevention of recurrences of peptic ulcers associated with Helicobacter pylori.

Patients, long-term NSAIDs:

- healing of gastric ulcer associated with the intake of NSAIDs;

- prevention of gastric ulcer and duodenal ulcer associated with the administration of NSAIDs in patients at risk.

Zollinger-Ellison syndrome or other conditions characterized by pathological hypersecretion.

Contraindications:

- Hypersensitivity to esomeprazole, substituted

benzimidazolam and other components included in the preparation;

- hereditary intolerance to fructose, glucose-galactose

malabsorption or sugar-isomaltase deficiency;

- children under 12 years of age (efficacy and safety not established);

- children age over 12 years according to other indications, except for gastroesophageal reflux disease;

- esomeprazole, like other inhibitors of the proton pump, should not be taken with atazanavir and nelfinavir;

- lactation period.

Carefully:

- Pregnancy;

severe renal failure (experience with use is limited).

Pregnancy and lactation:

At present, there is not enough evidence on the use of esomeprazole during pregnancy.

With the introduction of esomeprazole, no direct or indirect adverse effects on the development of the embryo or fetus have been identified in animals. The introduction of the racemic preparation also did not have any negative impact on animals during pregnancy, childbirth, and also during postnatal development.

Prescribe the drug to pregnant women only if the expected benefit to the mother exceeds the possible risk to the fetus. The use of the drug during lactation is contraindicated.

Dosing and Administration:

Inside. The tablet should be swallowed whole, washed down with liquid. Tablets can not be chewed or broken.

For patients with difficulty swallowing, you can dissolve tablets in half a glass of still water (do not use other liquids, since the protective shell of microgranules can dissolve), stirring until the tablet breaks, and then the slurry should be drunk immediately or for 15 minutes, then again fill the glass with water halfway, stir leftovers and drink. Do not chew or grind microgranules. For patients who can not swallow, the tablets should be dissolved in non-carbonated water and injected through a gastric tube. It is important that the selected syringe and probe are thoroughly tested. Guidance on the preparation and administration of the drug through the gastric tube is given in this section below.

Adults and children from the age of 12

Gastroesophageal reflux disease:

- treatment of erosive reflux esophagitis - 40 mg of esomeprazole once a day for 4 weeks. An additional 4-week course of treatment is recommended in cases where after the first course of healing, esophagitis does not occur or symptoms persist;

- long-term maintenance treatment after healing of erosive reflux esophagitis to prevent relapse - 20 mg once a day;

- symptomatic treatment of gastroesophageal reflux disease - 20 mg once a day to patients without esophagitis. If after 4 weeks of treatment the symptoms do not disappear, an additional examination of the patient should be carried out. After eliminating the symptoms, you can go to the drug intake mode "if necessary", i.e. accept esomeprazole 20 mg once a day with the resumption of symptoms. For patients taking NSAIDs and those at risk of developing gastric or duodenal ulcers, treatment is not recommended if necessary.

Adults

Peptic ulcer of the stomach and duodenum as part of a combination therapy for eradication with Helicobacter pylori:

- treatment of duodenal ulcers associated with Helicobacter pylori - esomeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg. All drugs are taken twice a day for 7 days;

- prevention of recurrences of peptic ulcers associated with Helicobacter pylori - esomeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg. All drugs are taken twice a day for 7 days.

Patients taking long-term NSAIDs:

- healing of gastric ulcer associated with the intake of NSAIDs - esomeprazole 20 mg or 40 mg once daily. Duration of treatment is 4-8 weeks;

- prevention of gastric ulcer and duodenal ulcer associated with the intake of NSAIDs in patients at risk - esomeprazole 20 mg or 40 mg once daily.

Zollinger-Ellison syndrome or other conditions characterized by pathological hypersecretion The recommended initial dose of esomeprazole is 40 mg twice daily. In the future, the dose is selected individually, the duration of treatment is determined by the clinical picture of the disease. There is an experience of application in the range from 80 mg to 120 mg of esomeprazole per day. When applying the drug in a dose above 80 mg, it is necessary to break the intake of the drug twice a day.

Renal insufficiency: dosage adjustment is not required. Liver failure: with mild and moderate hepatic insufficiency, dose adjustment is not required. For patients with severe hepatic insufficiency do not exceed the maximum daily dose - 20 mg.

Older patients: dosage adjustment is not required. Administration of the drug through a gastric tube When prescribing the drug through a gastric tube

1. Place the tablet in a syringe and fill the syringe with 25 ml of water and about 5 ml of air. For some probes, dilution of the preparation in 50 ml of drinking water may be required in order to prevent the probe from clogging the pellets with a tablet.

Immediately shake the syringe for about two minutes to dissolve the tablet.

3. Hold the syringe tipped up and make sure that the tip is not clogged.

4. Insert the tip of the syringe into the probe, continuing to hold it pointed upwards.

5. Shake the syringe and flip it down with a tip. Immediately insert 5-10 ml of dissolved drug into the probe. After the injection, return the syringe to its previous position and shake it (the syringe should be held up by the tip to avoid clogging the tip).

6. Turn the syringe tip down and insert another 5-10 ml of the drug into the probe. Repeat this until the syringe is empty.

7. If the remainder of the preparation is in the form of a sludge in the syringe, fill the syringe with 25 ml of water and 5 ml of air and repeat the operations described in paragraphs 5 and 6. For some probes, 50 ml of drinking water may be needed for this purpose.

Side effects:

According to the World Health Organization (WHO) undesirable effects classified according to their frequency of development is as follows: very often (> or = 1/10), often (> or = 1/100, <1/10), infrequently (> or = 1/1000, <1/100), rarely (> or = 1/10000, <1/1000) and very rarely (<1/10000); frequency is unknown (the frequency of occurrence of phenomena can not be determined on the basis of available data).

On the part of the hematopoiesis system

rarely: leukopenia, thrombocytopenia;

very rarely: agranulocytosis, pancytopenia.

From the central nervous system and sense organs

often: headache; infrequently: insomnia, dizziness, paresthesia, drowsiness, blurred vision; rarely: agitation, confusion, depression; very rarely: aggression, hallucinations.

From the gastrointestinal tract

often: abdominal pain, constipation, diarrhea, flatulence, nausea / vomiting; infrequently: dry mouth; rarely: a taste disorder, stomatitis, gastrointestinal candidiasis, hepatitis with or without jaundice; very rarely: liver failure, encephalopathy in patients with a history of liver disease;

frequency unknown: microscopic colitis (confirmed histologically).

From the respiratory system

rarely: bronchospasm.

From the skin side infrequently: dermatitis, itching, rash, hives;

rarely: alopecia, photosensitivity, malaise, excessive sweating; very rarely: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN).

From the side of the musculoskeletal system

infrequently: fractures of the neck of the thigh, bones of the wrist, vertebrae; rarely: arthralgia, myalgia; very rarely: muscle weakness.

From the urinary system

very rarely: interstitial nephritis; some patients reported the development of renal failure.

From the side of the reproductive system and mammary glands

very rarely: gynecomastia.

Allergic reactions

rarely: hypersensitivity reactions (eg, fever,angioedema

and anaphylactic reaction / anaphylactic shock).

Metabolic and nutritional disorders

infrequently: peripheral edema;

rarely: hyponatremia;

very rarely: hypomagnesemia; severe hypomagnesemia may correlate with hypocalcemia.

Laboratory indicators are infrequent: increased activity of "liver" transaminases.

Overdose:

At the moment, very rare cases of deliberate overdose are described. Oral administration of esomeprazole at a dose of 280 mg was accompanied by general weakness and symptoms from the gastrointestinal tract. A single dose of esomeprazole at a dose of 80 mg did not cause any negative consequences.

Specific antidotes are unknown. Esomeprazole binds to plasma proteins, so dialysis is ineffective. In case of an overdose, symptomatic and general supportive treatment should be performed.

Interaction:

Effect of esomeprazole on the pharmacokinetics of other drugs

Reduced acidity in the stomach in the treatment of esomeprazole may lead to a decrease or increase in absorption of other drugs, the absorption mechanism of which depends on the acidity of the medium.As with other drugs suppressing the secretion of hydrochloric acid, or antacids, treatment with esomeprazole may lead to a decrease in absorption of ketoconazole, itraconazole and erlotinib, and an increase in the absorption of such drugs as digoxin. The simultaneous use of esomeprazole at a dose of 20 mg once daily and digoxin increases the bioavailability of digoxin by 10% (the bioavailability of digoxin was increased by up to 30% in two out of ten patients).

It was shown that esomeprazole interacts with some antiretroviral drugs. The mechanisms and clinical significance of this interaction are not always known. An increase in pH on the background of esomeprazole therapy may affect absorption

antiretroviral drugs. It is also possible to interact at the level of the isoenzyme CYP2C19. With simultaneous use of esomeprazole and some antiretroviral drugs, such as atazanavir and nelfinavir, against the background of therapy with esomeprazole, there is a decrease in their concentration in the blood serum. Therefore, their simultaneous application is not recommended.

The simultaneous use of esomeprazole (40 mg once daily) with atazanavir 300mg / ritonavir 100 mg to healthy volunteers resulted in a significant reduction in the bioavailability of atazanavir (area under the concentration-time curve (AUC), Stach and Cmin in blood plasma decreased by approximately 75%). An increase in the dose of atazanavir to 400 mg did not compensate for the effects of esomeprazole on the bioavailability of atazanavir.

With the simultaneous use of esomeprazole and saquinavir, an increased concentration of saquinavir in the blood serum was noted, with the prescription with some other antiretroviral drugs, their concentration did not change. Esomeprazole inhibits CYP2C19, the main isoenzyme involved in its metabolism. The simultaneous use of esomeprazole with other drugs in the metabolism of which the isoenzyme CYP2C19, such as diazepam, citalopram, imipralshn, clomipramine, phenytoin , etc., can lead to an increase in the concentration of these drugs in the blood plasma and require a dose reduction. It is especially important to remember this interaction when using esomeprazole "as needed".

With simultaneous ingestion of esomeprazole at a dose of 30 mg and diazepam by 45%, the clearance of diazepam decreases, which is the substrate of the isoenzyme CYP2C19.

With simultaneous ingestion of esomeprazole 40 mg and phenytoin in patients with epilepsy, the residual concentration of phenytoin in the blood plasma increased by 13%. In this regard, it is recommended to control the concentration of phenytoin in the blood plasma at the beginning of treatment with esomeprazole and when it is withdrawn.

The use of esomeprazole at a dose of 40 mg once a day led to an increase in AUC and Cmax

voriconazole (substrate isoenzyme CYP2C19) by 15% and 41%, respectively.

When esomeprazole is administered orally at a dose of 40 mg to patients receiving warfarin, the coagulation time remained within the allowed values. However, several cases of a clinically significant increase in the INR index (an international normalized ratio) have been reported with simultaneous use of warfarin and esomeprazole. In this regard, monitoring of INR at the beginning and after the end of joint use of esomeprazole and warfarin or other coumarin derivatives is recommended.

The use of esomeprazole in a dose of 40 mg in healthy volunteers once a day 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.

In healthy volunteers, concomitant administration of either esomeprazole 40 mg or cisapride 32% increased the AUC value by 31% and increased T 1/2 cisapride by 31%; Cisapride in blood plasma did not change significantly. The slight prolongation of the QT interval, which was observed with monotherapy with cisapride, did not increase with the addition of esomeprazole.

A pharmacokinetic / pharmacodynamic interaction was observed between clopidogrel (loading dose 300 g / maintenance dose 75 mg) and esomeprazole (40 mg / day), which reduces the exposure of the active metabolite of clopidogrel by an average of 40% and reduces the maximum inhibition of ADP-induced platelet aggregation by an average of 14%.

When clopidogrel was used together with a fixed combination of esomeprazole (20 mg / day) and acetylsalicylic acid (81 mg / day), the clopidogrel active metabolite decreased by 40% compared to clopidogrel monotherapy, with the maximum levels of inhibition of ADP-induced platelet aggregation being the same .

In the course of observations and clinical studies, conflicting data were obtained on the presence or absence of an increased risk of developing cardiovascular complications; nevertheless,should be used with caution clopidogrel together with esomeprazole.

Some patients reported increased concentrations of methotrexate on the background of joint

application with proton pump inhibitors. When prescribing high doses of methotrexate, the possibility of temporary withdrawal of esomeprazole should be considered.

With simultaneous use of esomeprazole and tacrolimus, tacrolimus concentration in the blood serum increased. Shown, that esomeprazole does not cause clinically significant changes in the pharmacokinetics of amoxicillin and quinidine.

Studies evaluating the short-term concomitant use of esomeprazole and naproxen or rofecoxib have not revealed a clinically significant pharmacokinetic

interaction.

The effect of drugs on the pharmacokinetics of esomeprazole

The isozymes CYP2C19 and CYP3A4 are involved in the metabolism of esomeprazole. The combined use of esomeprazole and clarithromycin, an inhibitor of the isoenzyme CYP3A4 (500 mg twice daily), leads to a twofold increase in the AUC value for esomeprazole. The simultaneous use of esomeprazole and a combined inhibitor of isoenzymes CYP3A4 and CYP2C19, for example, voriconazole, can lead to an increase in the AUC of esomeprazole by more than 2 times.As a rule, in such cases, dosage correction of esomeprazole is not required. Correction of the dose of esomeprazole may be required in patients with severe impairment of liver function and with prolonged use.

Drugs that induce isoenzymes CYP2C19 and CYP3A4, such as rifampicin and preparations of St. John's wort, when administered with esomeprazole, can lead to a decrease in the plasma esomeprazole concentration by accelerating the metabolism of esomeprazole.

Special instructions:

In the presence of any anxiety symptoms (for example, such as significant spontaneous weight loss, frequent vomiting, dysphagia, vomiting with blood or melena), and in the presence of a stomach ulcer (or suspected gastric ulcer), the possibility of malignant neoplasm should be excluded, esomeprazole can lead to a smoothing of the symptoms and thus delay the setting of the correct diagnosis.

Patients taking the drug for a long period (especially more than 1 year) should be under regular medical supervision.

Hypomagnesemia.

A severe form of hypomagnesemia was observed in patients undergoing IPT treatment,such as esomeprazole, for at least three months, and in most cases with treatment during the year. There have been serious manifestations of hypomagnesemia, such as chronic fatigue, convulsions, delirium, convulsions, dizziness and ventricular arrhythmia, but they can begin

gradually and remain unnoticed. In most patients, hypomagnesemia disappeared after additional magnesium intake and discontinuation of PID.

For patients who may require long-term treatment or taking IPN in conjunction with digoxin or drugs that can cause hypomagnesemia (eg, diuretics), physicians should consider measuring the magnesium concentration before starting the PID and periodically during treatment.

The use of proton pump inhibitors, especially when used in large doses and for an extended period (> 1 year), can lead to

a moderate increase in the risk of a hip fracture, wrist bones and vertebral bodies, especially in the elderly or in the presence of other known risk factors.

The carried out researches allow to assume, that reception of the given preparations can raise the general risk of fractures on 10-40%. To some extent, this increase in risk may be a consequence of other factors. Patients at risk for developing osteoporosis should be treated in accordance with modern clinical guidelines and take in the required amount of vitamin D and calcium.

During the treatment of PID, the concentration of gastrin in the blood plasma is increased due to decreased intragastric secretion of hydrochloric acid. In patients taking PID for a long time, the formation of glandular cysts in the stomach is more often noted. These phenomena are caused by physiological changes due to inhibition of hydrochloric acid secretion. Cysts are benign and undergo reverse development. Patients on the "as needed" therapy regimen should be instructed to contact their physician if the symptoms change. Taking into account fluctuations in concentration

esomeprazole in the blood plasma when the drug is administered in the "if necessary" therapy regimen, the interaction of the drug with other drugs should be taken into account.

When prescribing esomeprazole for the eradication of Helicobacter pylori, the possibility of drug interaction for all components of triple therapy should be considered. Clarithromycin is a strong inhibitor of the isoenzyme CYP3A4, therefore, in the appointment of eradication therapy to patients receiving other drugs metabolized with the participation of the isoenzyme CYP3A4 (eg, cisapride), it is necessary to take into account possible contraindications and interaction of clarithromycin with these drugs.

Esomeprazole may decrease the absorption of vitamin B12 due to hypo- or achlorhydria. This should be taken into account when using the drug Neo-text in patients with insufficiency or with a risk of developing vitamin B12 deficiency with prolonged therapy.

The tablets contain sucrose, so one should not prescribe esomeprazole patients with hereditary intolerance to fructose, glucose-galactose malabsorption or sugar-isomaltase deficiency.

Special precautions for the destruction of unused medicinal product.

There is no need for special precautions when destroying an unused Neo-text product.

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

During the treatment with esomeprazole, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets are enteric, film-coated 20 mg, 40 mg.

Packaging:

For 7 tablets put in A1 / A1 blister.

For 2 or 4 blisters are placed in a cardboard box together with instructions for medical use.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children!

Shelf life:

2 years.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001513

Date of registration:16.02.2012

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

SALUTAS PHARMA, GmbH Germany

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp25.10.2015

Illustrated instructions

Instructions

Neo-Sext® (Neo-Zext®)