Nexium, pills 20mg, 28pcs

Composition

Active ingredient: 22.30 mg of esomeprazole magnesium trihydrate, which corresponds to 20 mg of esomeprazole. Auxiliary substances: glyceryl monostearate 40-55 1.70 mg, hyprolose 8.10 mg, hypromellose 17.00 mg, iron oxide red dye (E 172) 0.06 mg, iron oxide yellow dye (E 172) 0.02 mg, magnesium stearate 1.20 mg, methacrylic and ethacrylic acid copolymer (1: 1) 35.00 mg, microcrystalline cellulose 273.00 mg, paraffin 0.20 mg, macrogol 3.00 mg, polysorbate 80 0.62 mg, crospovidone. 5.70 mg, sodium stearyl fumarate 0.57 mg, sucrose spherical granules (sugar, spherical granules) (size 0.250-0.355 mm) 28.00 mg, titanium dioxide (E 171) 2.90 mg, talc 14.00 mg, triethyl citrate 10.00 mg

Pharmacological action

Pharmacotherapy group:

gastric glands secretion lowering agent-proton pump inhibitor

ATX Code: A02BC05

Pharmacodynamics

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

Mechanism of action

Esomeprazole is a weak base that converts to the active form in the highly acidic environment of the secretory tubules of the parietal cells of the gastric mucosa and inhibits the proton pump-the H+/K+enzyme ATPase, while inhibiting both basal and stimulated hydrochloric acid secretion.

Effect on gastric acid secretion

The effect of esomeprazole develops within 1 hour after oral use of 20 or 40 mg. When taking the drug daily for 5 days at a dose of 20 mg once a day, the average_cmax of hydrochloric acid after stimulation with pentagastrin decreases by 90% (when measuring the acid concentration 6-7 hours after taking the drug on the 5th day of therapy).

In patients with GERD and the presence of clinical symptoms, after 5 days of daily oral use of esomeprazole at a dose of 20 or 40 mg, the intragastric pH value above 4 was maintained for an average of 13 and 17 hours out of 24 hours. Against the background of esomeprazole at a dose of 20 mg/day, the intragastric pH value above 4 was maintained for at least 8,12 and 16 hours in 76,54 and 24% of patients, respectively. For 40 mg of esomeprazole, this ratio was 97,92, and 56%, respectively.

A correlation was found between the concentration of the drug in plasma and inhibition of hydrochloric acid secretion (the AUC parameter was used to estimate the concentration).

Therapeutic effect achieved by inhibiting the secretion of hydrochloric acid. When taking Nexium® at a dose of 40 mg, healing of reflux esophagitis occurs in approximately 78% of patients after 4 weeks of therapy and in 93% – after 8 weeks of therapy.

Treatment with Nexium® at a dose of 20 mg twice daily 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 disease after a week-long eradication course do not require subsequent monotherapy with drugs that lower the secretion of gastric glands to heal the ulcer and eliminate symptoms.

The efficacy of Nexium® for peptic ulcer bleeding was shown in a study in patients with endoscopically confirmed peptic ulcer bleeding.

Other effects associated with inhibition of hydrochloric acid secretion. During treatment with drugs that lower the secretion of gastric glands, the concentration of gastrin in plasma increases as a result of a decrease in acid secretion. Due to a decrease in the secretion of hydrochloric acid, the concentration of chromogranin A (CgA) increases. Increasing the concentration of CgA may affect the results of examinations for the detection of neuroendocrine tumors. To prevent this effect, therapy with proton pump inhibitors should be suspended 5-14 days before the CgA concentration study. If the CgA concentration has not returned to normal during this time, the study should be repeated.

In children and adult patients treated with esomeprazole for a long time, there is an increase in the number of enterochromaffin-like cells, probably associated with an increase in the concentration of gastrin in plasma. This phenomenon has no clinical significance.

Patients who have been taking medications that reduce the secretion of gastric glands for a long time are more likely to develop glandular cysts in the stomach. These phenomena are caused by physiological changes as a result of pronounced inhibition of hydrochloric acid secretion. Cysts are benign and undergo reverse development.

The use of drugs that suppress the secretion of hydrochloric acid in the stomach, including proton pump inhibitors, is accompanied by an increase in the content of microbial flora in the stomach, which is normally present in the gastrointestinal tract. The use of proton pump inhibitors may 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 probably Clostridium difficile (in hospitalized patients).

In two comparative studies conducted with ranitidine, Nexium® showed better efficacy in healing gastric ulcers in patients treated with NSAIDs, including selective COX-2 inhibitors. In two studies, Nexium® was shown to be highly effective in preventing gastric and duodenal ulcers in patients treated with NSAIDs (age group — over 60 years and/or with a history of peptic ulcer), including selective COX-2 inhibitors.

Pharmacokinetics

Absorption and distribution. Esomeprazole is unstable in an acidic environment, so tablets containing granules of the drug, the shell of which is resistant to the action of gastric juice, are used for oral use. In vivo, only a small fraction of esomeprazole is converted to the R-isomer. The drug is rapidly absorbed:  _Cmax in plasma is reached 1-2 hours after use. The absolute bioavailability of esomeprazole after a single dose of 40 mg is 64% and increases to 89% against the background of daily use 1 time per day. For a dose of 20 mg of esomeprazole, these values are 50 and 68%, respectively. V_ss in healthy people is approximately 0.22 l / kg. Esomeprazole binds to plasma proteins by 97%.

Food intake slows down and reduces the absorption of esomeprazole in the stomach, but this does not significantly affect the effectiveness of inhibiting the secretion of hydrochloric acid.

Metabolism and excretion. Esomeprazole is metabolized by the cytochrome P450 system. The main part is metabolized with the participation of the specific polymorphic isoenzyme MAP2C19, and hydroxylated and desmethylated metabolites of esomeprazole are formed. The remaining portion is metabolized by the CYP3A4 isoenzyme; the esomeprazole sulfide derivative is formed, which is the main metabolite detected in plasma.

The parameters listed below mainly reflect the nature of pharmacokinetics in patients with increased activity of the CYP2C19 isoenzyme.

Total Cl after a single dose of the drug is approximately 17 l / h, after repeated use-9 l / h. T_1/2-1.3 hours with systematic use 1 time per day. AUC increases with repeated use of esomeprazole. The dose-dependent increase in AUC with repeated use of esomeprazole is non-linear, which is a consequence of a decrease in metabolism during the first passage through the liver, as well as a decrease in systemic clearance, probably caused by inhibition of the CYP2C19 isoenzyme by esomeprazole and/or its sulfide derivatives. When taken daily once a day, esomeprazole is completely eliminated from the blood plasma in the interval between doses and does not accumulate.

The main metabolites of esomeprazole do not affect gastric acid secretion. When administered orally, up to 80% of the dose is excreted as metabolites in the urine, the remaining amount is excreted in the faeces. Less than 1% of unchanged esomeprazole is detected in the urine.

Features of pharmacokinetics in some groups of patients

Patients with reduced activity of the CYP2C19 isoenzyme. Approximately (2.9±1.5)% of the population has reduced activity of the CYP2C19 isoenzyme. In these patients, esomeprazole is primarily metabolized by CYP3A4. When esomeprazole is systematically administered 40 mg once a day, the average AUC value is 100% higher than this parameter in patients with increased activity of the CYP2C19 isoenzyme. Mean plasma cmax values in patients with reduced isoenzyme activity are increased by approximately 60%. These features do not affect the dose and method of use of esomeprazole.

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

Gender. After a single dose of 40 mg of esomeprazole, the average AUC value in women is 30% higher than that in men. When taking the drug daily once a day, there are no differences in pharmacokinetics in men and women. These features do not affect the dose and method of use of esomeprazole.

Liver failure. In patients with mild to moderate hepatic insufficiency, esomeprazole metabolism may be impaired. In patients with severe hepatic insufficiency, the metabolic rate is reduced, which leads to a 2-fold increase in the AUC value for esomeprazole.

Kidney failure. Pharmacokinetics have not been studied in patients with renal insufficiency. Since it is not esomeprazole itself that is eliminated through the kidneys, but its metabolites, it can be assumed that the metabolism of esomeprazole in patients with renal insufficiency does not change.

Children’s age. In children aged 12-18 years after repeated use of 20 and 40 mg of esomeprazole, the AUC and tmax values in blood plasma were similar to the AUC and tmax values in adults.

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 Helicobacter pylori-associated duodenal ulcer;
• prevention of relapses of Helicobacter pylori-associated peptic ulcer;
• long-term acid-suppressing therapy in patients who have suffered bleeding from a peptic ulcer (after intravenous use of drugs that lower the secretion of gastric glands), to prevent relapse;

Patients taking NSAIDs for a long time:

• healing of gastric ulcers associated with NSAIDs;
• prevention of gastric and duodenal ulcers associated with NSAIDs in patients at risk;
• Zollinger-Ellison syndrome or other conditions characterized by pathological hypersecretion of the gastric glands, including idiopathic hypersecretion.

Use during pregnancy and lactation

Currently, there is insufficient data on the use of Nexium® 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, and 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 Nexium®should not be prescribed during breast-feeding.

Contraindications

• hypersensitivity;
• hereditary fructose intolerance, glucose-galactose malabsorption or Saharsa-isomaltase failure;
• children up to age 12 years (due to the lack of data about the effectiveness and safety of the drug in this group of patients) and children over 12 years for other indications, except for gastroesophageal reflux disease;
• concomitant use of atazanavir and nelfinavir.

With caution — severe renal failure.

Side effects

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.

Nervous system disorders: 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, gastrointestinal candidiasis; very rarely-microscopic colitis.

Liver and biliary tract disorders: 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.

Blood and lymphatic system disorders: rarely-leukopenia, thrombocytopenia; very rarely-agranulocytosis, pancytopenia.

From the immune system: rarely — hypersensitivity reactions (e. g. fever, angioedema, anaphylactic reaction/anaphylactic shock).

Respiratory, thoracic and mediastinal disorders: rarely-bronchospasm.

From the side of the kidneys and urinary tract: very rarely — interstitial nephritis.

From the side of the visual organ: 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.

Common 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 2 out of 10 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 is co-administered with some antiretroviral drugs, such as atazanavir and nelfinavir, a decrease in their serum concentrations is observed during omeprazole therapy. 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 Nexium® 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 index increases have been reported INR with the combined use of warfarin and esomeprazole. It is recommended to monitor INR at the beginning and end of co-use of esomeprazole and warfarin or other coumarin derivatives.

According to the results of studies, a pharmacokinetic/pharmacodynamic interaction was noted between clopidogrel (loading dose-300 mg and maintenance dose-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 maximum inhibition of ADP-induced platelet aggregation by an average of 14%.

The clinical significance of this interaction is unclear.In a prospective study in patients receiving 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.

Omeprazole 40 mg increased 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.

Couse of cisapride with 40 mg of esomeprazole leads to an increase in the pharmacokinetic parameters of cisapride in healthy volunteers: AUC – by 32% and T_1/2-by 31%, but the_cmax of cisapride in plasma does not change significantly. Slight prolongation of the QT interval, which was observed with cisapride monotherapy, with the addition of Nexium® it did not increase (see “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.

Nexium® It 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 drugs 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.

Co-use of esomeprazole and a combined inhibitor of the CYP3A4 and CYP2C19 isoenzymes, such as 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.

For patients with difficulty swallowing, you can dissolve the tablets in half a glass of still water. Do not use other liquids, as the protective shell of microgranules may dissolve. When dissolving the tablet, stir the water until the tablet disintegrates and drink the microgranule suspension immediately or no later than within 30 minutes. Then fill the glass half full of water, stir the leftovers and drink. Do not chew or crush microgranules.

For patients who cannot swallow, tablets should be dissolved in still water and administered through a nasogastric tube. It is important that the selected syringe and probe are suitable for performing this procedure. Instructions for preparation and use of the drug through a nasogastric tube are given in the subsection “use of the drug through a nasogastric tube”.

Adults and children over 12 years

of age with GERD

Treatment of erosive reflux esophagitis: 40 mg once a day for 4 weeks. An additional 4-week course of treatment is recommended if esophagitis does not heal after the first course or if symptoms persist.

Long-term maintenance treatment of patients after erosive reflux esophagitis has healed to prevent relapse: 20 mg once a day.

Symptomatic treatment of GERD in patients without esophagitis: 20 mg once a day. If the symptoms do not disappear after 4 weeks of treatment, an additional examination of the patient should be performed. After the symptoms are resolved, you can switch to the “as needed” mode of taking the drug, i. e. in case of symptoms, take Nexium® 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 “as needed” mode is not recommended.

Adults

Peptic ulcer of the stomach and duodenum (as part of combination therapy)

Treatment of Helicobacter pylori-associated duodenal ulcer: Nexium ® 20 mg, amoxicillin 1 g and clarithromycin 500 mg. All medications are taken 2 times a day for 1 week.

Prevention of recurrent peptic ulcers associated with Helicobacter pylori: Nexium ® 20 mg, amoxicillin 1 g and clarithromycin 500 mg. All medications are taken 2 times 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), for the prevention of relapse

Nexium ® 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 NSAIDs: Nexium® 20 or 40 mg once a day. The duration of treatment is 4-8 weeks.

Prevention of stomach and duodenal ulcers associated with NSAIDs: Nexium®20 or 40 mg once a day.

Conditions associated with abnormal hypersecretion of gastric glands, including Zollinger-Ellison syndrome and idiopathic hypersecretion

The recommended starting dose is Nexium 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.

Special patient groups

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

Liver failure: 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.

use of the drug through a nasogastric tube

Overdose

Symptoms: 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 gastrointestinal symptoms. Single dose of 80 mg Nexium® it did not cause any negative consequences.

Treatment: symptomatic and general maintenance therapy. Esomeprazole binds well to plasma proteins, so dialysis is ineffective. The antidote of esomeprazole is unknown.

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 Nexium® 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.

Influence on the ability to drive a car and other mechanisms. Due to the fact that dizziness, blurred vision and drowsiness may occur during therapy with Nexium®, caution should be exercised when driving vehicles and other mechanisms.

Form of production

Tablets

Storage conditions

At a temperature not exceeding 25°C, in the original packaging, in places not accessible to children.

Shelf

life is 3 years. Do not use after the expiration date indicated on the package.

Active ingredient

Esomeprazole

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

Pregnant women as prescribed by a doctor, Children over 12 years of age, Children as prescribed by a doctor, Adults as prescribed by a doctor

Indications

Gastrointestinal infections caused by Helicobacter Pylori, Reflux Esophagitis, Gastric and Duodenal ulcers