Esomeprazole enteric-Soluble tablets 20mg, 28pcs

Composition

1 tablet, coated,20 mg contains:

Composition of the tablet core:

Active ingredient: esomeprazole magnesium dihydrate-21.7 mg (based on esomeprazole-20 mg).

Excipients: low-substituted hyprolose (hydroxypropylcellulose), pregelatinized corn starch, colloidal silicon dioxide, mannitol, sodium stearyl fumarate, microcrystalline cellulose, type 200, sodium carboxymethyl starch.

Composition of the tablet shell: hypromellose, macrogol-6000, acrylysis II yellow 493Z220000 (methacrylic acid and ethyl acrylate copolymer (1: 1), talc, titanium dioxide, poloxamer 407, calcium silicate, sodium bicarbonate, iron oxide yellow dye, sodium lauryl sulfate).

Indications

Gastroesophageal reflux disease:

– treatment of erosive reflux esophagitis;

– long-term maintenance treatment after healing of erosive reflux esophagitis to prevent relapse;

– symptomatic treatment of gastroesophageal reflux disease.

Peptic ulcer of the stomach and duodenum

As part of combination therapy:

– treatment of duodenal ulcer associated with Helicobacter pylori;

– prevention of relapses of peptic ulcer associated with Helicobacter pylori.

Long-term acid-suppressing therapy in patients who have suffered bleeding from a peptic ulcer (after intravenous use of drugs that reduce the secretion of gastric glands, to prevent relapse).

Patients taking NSAIDs for a long time:

– healing of stomach ulcers associated with NSAID use;

– prevention of gastric and duodenal ulcers associated with NSAID use in patients at risk.

Zollinger-Ellison syndrome or other conditions characterized by abnormal hypersecretion of the gastric glands, including idiopathic hypersecretion.

Use during pregnancy and lactation

Currently, there are insufficient data on the use of esomeprazole during pregnancy. The results of epidemiological studies of omeprazole, which is a racemic mixture, showed no fetotoxic effect or fetal development disorders.

When esomeprazole was administered to animals, no direct or indirect negative effects on the development of the embryo or fetus were detected. The introduction of a racemic mixture of the drug also did not have any negative effects on animals during pregnancy, childbirth, or postnatal development.

Prescribe the drug to pregnant women only if the expected benefit to the mother exceeds the possible risk to the fetus.

It is not known whether esomeprazole is excreted in breast milk, so it is not recommended to prescribe esomeprazole during breast-feeding.

Contraindications

Hypersensitivity to esomeprazole, substituted benzimidazoles or other ingredients that make up the drug.

Hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrose-isomaltase deficiency.

Children under 12 years of age (due to the lack of data on the effectiveness and safety of the drug in this group of patients) and children over 12 years of age for other indications, except for gastroesophageal reflux disease.

Esomeprazole should not be co-administered with atazanavir and nelfinavir(see section “Interactions with other medicinal products”).

Breast-feeding period.

With caution

Severe renal failure (limited experience), pregnancy.

Side effects

The frequency of side effects is given in the following gradation (World Health Organization classification): very common (≥1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10000, < 1/1000); very rare (

Skin and subcutaneous tissue disorders: infrequently-dermatitis, pruritus, rash, urticaria; rarely-alopecia, photosensitization; very rarely-erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Musculoskeletal and connective tissue disorders: rarely-arthralgia, myalgia; very rarely-muscle weakness.

From the nervous system: often-headache; infrequently-dizziness, paresthesia, drowsiness; rarely-taste disorders.

Mental disorders: infrequently-insomnia; rarely-depression, agitation, confusion; very rarely-hallucinations, aggressive behavior.

From the gastrointestinal tract: often-abdominal pain, constipation, diarrhea, flatulence, nausea/vomiting; infrequently-dry mouth; rarely-stomatitis, candidiasis of the gastrointestinal tract; very rarely-microscopic colitis (confirmed histologically).

From the liver and biliary tract: infrequently-increased activity of “liver” enzymes; rarely-hepatitis (with or without jaundice); very rarely – liver failure, encephalopathy in patients with liver diseases.

From the genitals and breast: very rarely – gynecomastia.

From the blood and lymphatic system: rarely-leukopenia, thrombocytopenia; very rarely-agranulocytosis, pancytopenia.

Immune system disorders: rarely – hypersensitivity reactions (e. g. fever, angioedema, anaphylactic reaction/anaphylactic shock).

Respiratory, thoracic and mediastinal disorders: rarely-bronchospasm.

Renal and urinary tract disorders: very rare – interstitial nephritis.

From the side of the organ of vision: rarely-blurred vision.

From the side of metabolism and nutrition: infrequently-peripheral edema; rarely-hyponatremia; very rarely-hypomagnesemia; hypocalcemia due to severe hypomagnesemia, hypokalemia due to hypomagnesemia.

General disorders: rarely-malaise, sweating.

Interaction

Effect of esomeprazole on the pharmacokinetics of other drugs

A decrease in the secretion of hydrochloric acid in the stomach during treatment with esomeprazole and other proton pump inhibitors may lead to a decrease or increase in the absorption of drugs whose absorption depends on the acidity of the medium. Similar to other drugs that reduce the acidity of gastric juice, treatment with esomeprazole may reduce the absorption of ketoconazole, itraconazole and erlotinib and increase the absorption of drugs such as digoxin. Couse of omeprazole at a dose of 20 mg once a day and digoxin increases the bioavailability of digoxin by 10% (digoxin bioavailability increased by up to 30% in two out of ten patients).

Omeprazole has been shown to interact with some antiretroviral drugs. The mechanisms and clinical significance of these interactions are not always known. An increase in the pH value during omeprazole therapy may affect the absorption of antiretroviral drugs. Interaction at the level of the CYP2C19 isoenzyme is also possible. When omeprazole and some antiretroviral drugs, such as atazanavir and nelfinavir, are co-administered with omeprazole, their serum concentrations decrease. Therefore, their simultaneous use is not recommended. Co-use of omeprazole (40 mg once daily) with atazanavir 300 mg/ritonavir 100 mg in healthy volunteers resulted in a significant reduction in the bioavailability of atazanavir (AUC, _cmax, and_cmin decreased by approximately 75%). Increasing the dose of atazanavir to 400 mg did not compensate for the effect of omeprazole on the bioavailability of atazanavir.

When omeprazole and saquinavir were co-administered, an increase in the concentration of saquinavir in the serum was noted; when used with some other antiretroviral drugs, their concentration did not change. Given the similar pharmacokinetic and pharmacodynamic properties of omeprazole and esomeprazole, co-use of esomeprazole with antiretroviral drugs such as atazanavir and nelfinavir is not recommended.

Esomeprazole inhibits CYP2C19, the main isoenzyme involved in its metabolism. Accordingly, the combined use of esomeprazole with other drugs that are metabolized by the CYP2C19 isoenzyme, such as diazepam, citalopram, imipramine, clomipramine, phenytoin, etc., may lead to an increase in plasma concentrations of these drugs, which, in turn, may require dose reduction. This interaction is especially important to keep in mind when using esomeprazole in the “as needed” mode. Co-use of 30 mg of esomeprazole and diazepam, which is a substrate of the CYP2C19 isoenzyme, resulted in a 45% decrease in the clearance of diazepam.

The use of esomeprazole at a dose of 40 mg resulted in an increase in the residual concentration of phenytoin in patients with epilepsy by 13%. In this regard, it is recommended to monitor the concentration of phenytoin in plasma at the beginning of treatment with esomeprazole and when it is discontinued.

The use of omeprazole at a dose of 40 mg once a day resulted in an increase in the AUC and_cmax of voriconazole (a substrate of the CYP2C19 isoenzyme) by 15% and 41%, respectively.

Co-use of warfarin with 40 mg of esomeprazole does not change the coagulation time in patients taking warfarin for a long time. However, several cases of clinically significant increases in INR (International normalized ratio) have been reported when warfarin and esomeprazole are co-administered.It is recommended to monitor INR at the beginning and end of co-use of esomeprazole and warfarin or other coumarin derivatives.

The results of the trials showed a pharmacokinetic/pharmacodynamic interaction between clopidogrel (loading dose of 300 mg and a maintenance dose of 75 mg/day) and esomeprazole (40 mg/day orally), which leads to a decrease in exposure to the active metabolite of clopidogrel by an average of 40% and a decrease of the maximal inhibition of ADP-induced platelet aggregation by an average of 14%.

The clinical significance of this interaction is not clear. In a prospective study in patients treated with placebo or omeprazole at a dose of 20 mg / day simultaneously with clopidogrel and acetylsalicylic acid (ASA), and in the analysis of clinical outcomes of large-scale randomized trials, no increased risk of cardiovascular complications was shown with the combined use of clopidogrel and proton pump inhibitors, including esomeprazole.

The results of a number of observational studies are contradictory and do not provide an unambiguous answer about the presence or absence of an increased risk of thromboembolic cardiovascular complications with the combined use of clopidogrel and proton pump inhibitors.

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

The use of omeprazole at a dose of 40 mg resulted in an increase in the_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.

Co-use of cisapride with 40 mg of esomeprazole resulted in an increase in the pharmacokinetic parameters of cisapride in healthy volunteers: AUC-by 32% and half-life by 31%, but the maximum concentration of cisapride in plasma did not change significantly. The slight prolongation of the QT interval, which was observed with cisapride monotherapy, did not increase with the addition of esomeprazole (see the section “Special instructions”).

When esomeprazole and tacrolimus were co-administered, an increase in the concentration of tacrolimus in the blood serum was noted.

In some patients, an increase in the concentration of methotrexate was noted against the background of co-use with proton pump inhibitors. When using high doses of methotrexate, temporary discontinuation of esomeprazole should be considered.

Esomeprazole does not cause clinically significant changes in the pharmacokinetics of amoxicillin and quinidine.

Studies evaluating the short-term co-use of esomeprazole and naproxen or rofecoxib did not reveal a clinically significant pharmacokinetic interaction.

Effect of medicinal products on the pharmacokinetics of esomeprazole

The isoenzymes CYP2C19 and CYP3A4 are involved in the metabolism of esomeprazole. Co-use of esomeprazole with clarithromycin (500 mg twice daily), which inhibits the CYP3A4 isoenzyme, leads to a 2-fold increase in the AUC of esomeprazole. Concomitant use of esomeprazole and a combined inhibitor of the CYP3A4 and CYP2C19 isoenzymes, for example, voriconazole, can lead to a more than 2-fold increase in the AUC value for esomeprazole. As a rule, no dose adjustment of esomeprazole is required in such cases. Dose adjustment of esomeprazole may be required in patients with severe hepatic impairment and long-term use of esomeprazole.

Drugs that induce the isoenzymes CYP2C19 and CYP3A4, such as rifampicin and St. John’s wort, when used together with esomeprazole, can lead to a decrease in the concentration of esomeprazole in blood plasma due to the acceleration of esomeprazole metabolism.

How to take, course of use and dosage

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

Adults and children from 12 years of age

Gastroesophageal reflux disease

Treatment of erosive reflux esophagitis: 40 mg once a day for 4 weeks.

An additional 4-week course of treatment is recommended in cases where healing of esophagitis does not occur after the first course 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 daily in patients without esophagitis. If after 4 weeks of treatment the symptoms do not disappear, an additional examination of the patient should be performed. After the symptoms are eliminated, you can switch to the “if necessary” mode of taking the drug, i. e. take esomeprazole 20 mg once a day if symptoms resume. For patients taking NSAIDs who are at risk of developing gastric or duodenal ulcers, treatment in the “if necessary” mode is not recommended.

Adults

Peptic ulcer of the stomach and duodenum

As part of the 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 medications are taken twice a day for 1 week;

* prevention of recurrent peptic ulcers associated with Helicobacter pylori: esomeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg. All medications are taken twice a day for 1 week.

Long-term acid-suppressing therapy in patients who have suffered bleeding from a peptic ulcer (after intravenous use of drugs that reduce the secretion of gastric glands, to prevent relapse)

Esomeprazole 40 mg once a day for 4 weeks after the end of intravenous therapy with drugs that reduce the secretion of gastric glands.

Patients taking NSAIDs for a long time:

· healing of stomach ulcers associated with NSAID use: esomeprazole 20 mg or 40 mg once a day: the duration of treatment is 4-8 weeks;

· prevention of gastric and duodenal ulcers associated with NSAID use: esomeprazole 20 mg or 40 mg once a day.

Conditions associated with abnormal gastric gland hypersecretion, including Zollinger-Ellison syndrome and idiopathic hypersecretion.

The recommended starting dose is esomeprazole 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 experience of using the drug in doses up to 120 mg 2 times a day.

Renal failure: no dose adjustment is required. However, experience with esomeprazole in patients with severe renal insufficiency is limited; therefore, caution should be exercised when prescribing the drug to such patients (see section “Pharmacokinetics”).

Hepatic insufficiency: in mild to moderate hepatic insufficiency, no dose adjustment is required. For patients with severe hepatic insufficiency, the maximum daily dose should not exceed 20 mg.

Elderly patients: no dose adjustment is required.

Overdose

At the moment, extremely rare cases of intentional overdose have been described. Oral use of esomeprazole at a dose of 280 mg was accompanied by general weakness and symptoms from the gastrointestinal tract. A single dose of 80 mg of esomeprazole did not cause any negative consequences. The antidote of esomeprazole is unknown. Esomeprazole binds well to plasma proteins, so dialysis is ineffective.

In case of overdose, it is necessary to conduct symptomatic and general supportive treatment.

Special instructions

In the presence of any alarming symptoms (for example, such as significant spontaneous weight loss, repeated vomiting, dysphagia, vomiting with blood or melena), as well as in the presence of a stomach ulcer (or if a stomach ulcer is suspected), the presence of a malignant neoplasm should be excluded, since treatment with esomeprazole may smooth out the symptoms and delay the diagnosis.

In rare cases, patients who took omeprazole for a long time, histological examination of biopsies of the gastric mucosa revealed atrophic gastritis.

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

Patients taking esomeprazole “as needed” should be instructed to contact their doctor if the nature of symptoms changes. Taking into account fluctuations in the concentration of esomeprazole in plasma when prescribing therapy “as needed”, it is necessary to take into account the interaction of the drug with other drugs (see the section “Interaction with other drugs”). When prescribing esomeprazole for the eradication of Helicobacter pylori, the possibility of drug interactions for all components of triple therapy should be taken into account. Clarithromycin is a potent inhibitor of CYP3A4, so when prescribing eradication therapy to patients receiving other drugs that are metabolized with the participation of CYP3A4 (for example, cisapride), it is necessary to take into account possible contraindications and interactions of clarithromycin with these drugs.

Impact on laboratory test results

Esomeprazole can cause an increase in the level of chromogranin A, which can distort the results of examinations in neuroendocrine tumors. To avoid these problems, treatment with esomeprazole should be temporarily suspended, at least five days before the determination of chromogranin A.

Esomeprazole, like all acid-lowering medications, can lead to decreased absorption_{of vitamin B12} (cyanocobalamin) due to hypo – or achlorhydria. This should be considered in patients with risk factors for reduced vitamin_{B12 absorption} during long-term therapy.

When using proton pump inhibitors, especially when used in high doses and for a long period (>1 year), there is a possible risk of fractures of the femoral neck, wrist bones and vertebrae (especially in elderly patients).

Influence on the ability to drive vehicles and mechanisms

Due to the fact that dizziness, blurred vision and drowsiness may occur during esomeprazole therapy, care should be taken when driving vehicles and other mechanisms.

Storage conditions

Store in a dark place at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf

life is 2 years.

Do not use after the expiration date.

Active ingredient

Esomeprazole

Conditions of release from pharmacies

By prescription

Dosage form

Tablets