Esomeprazole enteric-Soluble tablets 40mg, 28pcs

Composition

• Active ingredient: esomeprazole magnesium dihydrate 43.6 mg, which corresponds to the content of esomeprazole 40 mg;
• Excipients: hyprolose viscosimetry (hydroxypropyl cellulose) – 28 mg, corn starch pregelatinization – 74.4 mg, silicon dioxide colloid – 4 mg, mannitol – 46 mg, sodium fumarate 4 mg, microcrystalline cellulose – 280 mg.
• the composition of the film shell: transparent Opadry – 16 mg (hypromellose (hydroxypropyl methylcellulose) – 12.8 mg, macrogol (polyethylene glycol) – 3.2 mg); Acrylic-green – 44 mg (copolymer of methacrylic acid and ethacrylate (1: 1) – 29.04 mg, silicon dioxide colloid – 0.44 mg sodium bicarbonate – 0.44 mg, sodium lauryl sulfate – 0.22 mg, iron oxide yellow – 0.308 mg, dye Indigo – 0.352 mg, dye brilliant blue – 0.132 mg, talc – 7.26 mg, titanium dioxide – 5.808 mg); triethylcitrate – 4 mg.

Pharmacological action

Proton pump inhibitor.

Pharmacokinetics

Absorption and distribution.

Esomeprazole is unstable in an acidic environment, so tablets coated with enteric soluble membranes are used for oral use. In vivo, only a small fraction of esomeprazole is converted to the R-isomer.

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.

The drug is rapidly absorbed: the maximum concentration (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 intake once a day.

For a 20 mg dose of esomeprazole, these values are 50% and 68%, respectively. The volume of distribution at steady-state concentration in healthy individuals is approximately 0.22 l / kg of body weight. Esomeprazole binds to plasma proteins by 97%.

Metabolism and excretion.

Esomeprazole is metabolized by cytochrome P450 isoenzymes. The main part is metabolized with the participation of a specific polymorphic isoenzyme CYP2C19, while hydroxylated and demethylated metabolites of esomeprazole are formed.

The remaining part is metabolized by the CYP3A4 isoenzyme, and 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 clearance is approximately 17 l / h after a single dose of the drug and 9 l / h after repeated use. The half-life (T 1/2) is 1.3 hours when taken systematically once a 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 pass ” 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 the secretion of hydrochloric acid in the stomach. When administered orally, up to 80% of the dose is excreted in the form of metabolites by the kidneys, the other part – by the intestines. Less than 1% of unchanged esomeprazole is detected in the urine.

Features of pharmacokinetics in some groups of patients, Approximately 2.9 ± 1.5% of the population has a reduced activity of the CYP2C19 isoenzyme. In such patients, esomeprazole is mainly metabolized by the CYP3A4 isoenzyme.

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. The average values of maximum plasma concentrations in patients with reduced isoenzyme activity are increased by approximately 60%.

These features do not affect the dose and method of use of esomeprazole. In elderly patients (71-80 years), the metabolism of esomeprazole does not undergo significant changes.

After a single 40 mg dose of esomeprazole, the mean AUC in women is 30% higher than 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.

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.

Pharmacokinetics have not been studied in patients with renal insufficiency.

Since it is not esomeprazole itself that is eliminated through the kidneys, but its metabolite, 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 use of 20 mg and 40 mg esomeprazole, the AUC value and time to reach maximum concentration (TMAX) in blood plasma were similar to the AUC and TMAX values in adults.

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 enzyme H+/K+ – ATPase, while inhibiting both basal and stimulated secretion of hydrochloric acid.

Effect on the secretion of hydrochloric acid in the stomach.

After oral use of 20 mg or 40 mg, the effect of esomeprazole develops within 1 hour. When taking the drug daily for 5 days at a dose of 20 mg once a day, the average maximum concentration 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 gastroesophageal reflux disease (GERD) and the presence of clinical symptoms after 5 days of daily oral use of esomeprazole at a dose of 20 mg or 40 mg, the intragastric pH value above 4.0 was maintained for an average of 13 and 17 hours out of 24 hours.

When esomeprazole was administered at a dose of 20 mg per day, intragastric pH values above 4.0 were maintained for at least 8,12, and 16 hours in 76%,54%, and 24% of patients, respectively.

A correlation was found between the concentration of the drug in plasma and inhibition of hydrochloric acid secretion (the AUC parameter – area under the “concentration – time”curve was used to estimate the concentration. Therapeutic effect achieved by inhibiting the secretion of hydrochloric acid.

When taking the drug at a dose of 40 mg, healing of reflux esophagitis occurs in approximately 78% of patients after 4 weeks of therapy and in 93% of patients after 8 weeks of therapy.

Treatment with esomeprazole 20 mg twice daily in combination with appropriate antibiotics for one week results in 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 treat ulcers and eliminate symptoms. Esomeprazole has been shown to be effective in endoscopically confirmed peptic ulcer bleeding.

Other effects associated with inhibition of hydrochloric acid secretion During treatment with drugs that reduce the secretion of gastric glands, the concentration of gastrin in plasma increases as a result of a decrease in hydrochloric 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, it is necessary to temporarily stop taking esomeprazole 5 days before the CgA concentration study.

In patients treated with esomeprazole for a long time, an increase in the number of enterochromaffin-like cells was observed, probably due to an increase in the concentration of gastrin in plasma.

Patients who take drugs that reduce the secretion of gastric glands for a long period of time, the formation of glandular cysts in the stomach is more common. 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 Campylibacter spp. and, probably, Clostridium difficile in hospitalized patients.

In two comparative studies conducted with ranitidine, esomeprazole showed better efficacy in the treatment of gastric ulcers in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors.

Clinical pharmacology

Inhibitor of H+ – K+ – ATPASE.

Indications

• Erosive reflux esophagitis;
• gERD;
• duodenal ulcer associated with Helicobacter pylori;
• prevention of relapses of peptic ulcer associated with Helicobacter pylori;
• gastric and duodenal ulcers due to NSAID use.

Contraindications

• Hypersensitivity to esomeprazole, substituted benzimidazoles or other components of the drug;
• 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);
• Children aged from 12 to 18 years for all indications, except for GERD;
• Concomitant use with atazanavir and nelfinavir.

Side effects

Nervous system disorders: often-headache; infrequently-drowsiness, insomnia, dizziness, paresthesia; rarely-agitation, confusion, depression; very rarely-aggressive behavior, hallucinations.

Respiratory system disorders: rarely-bronchospasm.

Disorders of the digestive system: often-abdominal pain, diarrhea, flatulence, nausea, vomiting, constipation; infrequently-dry mouth, increased activity of “liver” enzymes; rarely-stomatitis, gastrointestinal candidiasis, hepatitis (with or without jaundice); very rarely – liver failure, hepatic encephalopathy in patients with a history of liver diseases, microscopic colitis.

Renal and urinary tract disorders: very rare – interstitial nephritis; frequency unknown-renal failure.

Disorders of the reproductive system: very rarely – gynecomastia.

Musculoskeletal disorders: rarely-arthralgia, myalgia; very rarely-muscle weakness; frequency unknown – fractures of the femoral neck, wrist bones, vertebrae.

Skin disorders: infrequently-pruritus, rash, urticaria, dermatitis, peripheral edema; rarely-alopecia, photosensitization, malaise, increased sweating; very rarely-Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.

Hematopoietic disorders: rarely-leukopenia, thrombocytopenia; very rarely-agranulocytosis, pancytopenia.

Sensory disorders: infrequently-blurred vision; rarely-taste disorders.

Allergic reactions: rarely – hypersensitivity reactions (for example, fever, angioedema, anaphylactic reaction/anaphylactic shock).

How to take, course of use and dosage

Inside. The tablet should be swallowed whole, without chewing, with a sufficient amount of water. Treatment of erosive reflux esophagitis: 40 mg 1 time / 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, prevention of relapses: 20 mg 1 time/day.

Symptomatic treatment of GERD: 20 mg 1 time / day 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 eliminating the symptoms, you can switch to the “if necessary” mode of taking the drug-20 mg 1 time/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.

In combination therapy for Helicobacter pylori eradication:

Treatment of Helicobacter pylori-associated duodenal ulcers: Esomeprazole Canon 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg. All medications are taken 2 times a day for 1 week.

Prevention of recurrent peptic ulcer associated with Helicobacter pylori: Esomeprazole Canon 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg. All medications are taken 2 times a day for 1 week.

Long-term acid-suppressive 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 Canon 40 mg 1 time/day for 4 weeks after intravenous use of drugs that reduce the secretion of gastric glands.

Treatment of stomach ulcers caused by NSAIDs: Esomeprazole Canon 20 mg 1 time / day; duration of treatment 4-8 weeks.

Prevention of gastric and duodenal ulcers caused by NSAID use: Esomeprazole Canon 20 mg 1 time / day.

Conditions characterized by abnormal hypersecretion of the gastric glands, including Zollinger-Ellison syndrome and idiopathic hypersecretion: the recommended initial dose of Esomeprazole Canon is 40 mg 2 times / day.

Further, the dose is selected individually, the duration of treatment is determined by the clinical picture of the disease. There is experience with the use of 80 to 160 mg of esomeprazole per day, if the drug is taken more than 80 mg / day, it is recommended to divide the required dose into 2 doses.

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

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.

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

During the treatment period, dizziness, blurred vision and drowsiness may occur, so caution should be exercised when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Active ingredient

Esomeprazole

Conditions of release from pharmacies

By prescription

Dosage form

Tablets