Nexium, pellets and granules 10mg, 28pcs

Composition

Active ingredient:

esomeprazole sodium 10 mg

Pharmacological action

Nexium is a proton pump inhibitor.

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 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 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 2 times a 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 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.

Patients treated with esomeprazole for a long time showed an increase in the number of enterochromaffin-like cells, probably associated with an increase in the concentration of gastrin in plasma.

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.

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. VSS at steady state in healthy individuals is approximately 0.22 l / kg of body weight. 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 a specific polymorphic isoenzyme SUR 2 With 19, 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. T1 / 2 — 1.3 h 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

Approximately (2.9±1.5)% of the population has reduced activity of the CYP2C19 isoenzyme. In these patients, esomeprazole is mainly metabolized by CYP3A4. When esomeprazole is systematically administered 40 mg once a day, the average AUC value is 100% higher than in patients with increased activity of the isoenzyme CYP2C19. 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.

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

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.

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 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 use of 20 and 40 mg of esomeprazole, the AUC value of iTmax in blood plasma was similar to the AUC and Tmax values in adults.

Indications

for GERD:

• treatment of erosive reflux esophagitis;
• long-term maintenance treatment after healing of erosive reflux esophagitis to prevent relapse;
• symptomatic treatment of gastroesophageal reflux disease;
• gastric and duodenal ulcer (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 experienced 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 stomach 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 abnormal hypersecretion of the gastric glands, including idiopathic hypersecretion.

Use during pregnancy and lactation

Currently, there are no data on the use of Nexium in pregnancy. Prescribing the drug during this period is possible only if the intended benefit to the mother exceeds the potential risk to the fetus.

Currently, it is not known whether esomeprazole is excreted in breast milk, so Nexium should not be prescribed during breastfeeding.

Experimental animal studies have not shown any negative effects of esomeprazole on the development of the embryo or fetus. The use of the racemic drug also did not have any negative effects on the course of pregnancy in animals, childbirth, and postnatal development.

Contraindications

• hypersensitivity to esomeprazole, substituted benzimidazoles or other ingredients that are part of the product;
• 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

Are Common: headache, abdominal pain, diarrhea, flatulence, nausea/vomiting, constipation.

Infrequently: dermatitis, pruritus, rash, urticaria, drowsiness, insomnia, dizziness, paresthesia, dry mouth, blurred vision, peripheral edema, increased activity of liver enzymes.

Rarely: hypersensitivity reactions (e. g. fever, angioedema, anaphylactic reaction/anaphylactic shock), bronchospasm, hepatitis (with or without jaundice), arthralgia, myalgia, leukopenia, thrombocytopenia, depression, hyponatremia, agitation, confusion, taste disorders, stomatitis, gastrointestinal candidiasis, alopecia, photosensitivity, malaise, sweating.

Very rarely: agranulocytosis, pancytopenia, hallucinations, aggressive behavior, liver failure, encephalopathy in patients with liver diseases, muscle weakness, interstitial nephritis, gynecomastia, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.

Interaction

Effect of esomeprazole on the pharmacokinetics of other drugs

When using Nexium simultaneously with other drugs, the absorption mechanism of which depends on the acidity of the medium, it is possible to reduce or increase the absorption of other drugs. As with other acid-suppressing drugs or antacids, treatment with esomeprazole may reduce the absorption of ketoconazole or itraconazole. The combined use of Nexium with drugs that are metabolized by CYP2C19, such as diazepam, citalopram, imipramine, clomipramine, and phenytoin, may lead to an increase in the concentration of these drugs in plasma and require a reduction in their doses.

Co-use of 30 mg of Nexium and diazepam reduces the clearance of the enzyme-substrate complex (CYP2C19-diazepam) by 45%. Concomitant use of Nexium at a dose of 40 mg increases the residual concentrations of phenytoin in the blood plasma of patients with epilepsy by 13% (it is recommended to monitor the concentration of phenytoin in the blood plasma when prescribing esomeprazole and when it is discontinued).

In healthy volunteers, co-use of cisapride with 40 mg of Nexium resulted in a 32% increase in cisapride AUC and a 31% increase in cisapride T1 / 2, but plasma concentrations of cisapride did not change significantly. The slight prolongation of the QT interval, which was observed with cisapride monotherapy, did not increase with the addition of Nexium.

When used concomitantly, Nexium does not cause clinically significant changes in the pharmacokinetic parameters of amoxicillin, quinidine and warfarin.

Effect of drugs on the pharmacokinetics of esomeprazole.

With simultaneous use of Nexium with clarithromycin (500 mg 2 times / day) The AUC of esomeprazole is increased 2-fold (no dose adjustment of Nexium is required).

How to take, course of use and dosage

For the treatment of erosive reflux esophagitis, the drug is prescribed in a single dose of 40 mg 1 time/day for 4 weeks. An additional 4-week course of therapy is recommended in cases where symptoms of the disease persist after the first course.

For long-term maintenance therapy of patients with cured esophagitis, the drug is prescribed 20 mg 1 time/day to prevent relapse.

For symptomatic treatment of gastroesophageal reflux disease without esophagitis, the drug is prescribed at a dose of 20 mg 1 time/day. 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, i. e. take Nexium 20 mg 1 time / day if symptoms occur before they are removed.

For the eradication of Helicobacter pylori, for the treatment of duodenal ulcers associated with Helicobacter pylori, for the prevention of relapse of peptic ulcers associated with Helicobacter pylori, Nexium is prescribed in a single dose of 20 mg, amoxicillin-1 g, clarithromycin-500 mg. All medications are taken 2 times a day for 7 days.

When prescribing the drug to patients with impaired renal function, no dose adjustment is required. The drug is used with caution in patients with severe renal insufficiency due to the limited clinical experience of its use in this category of patients. When Nexium is prescribed to patients with mild or moderate hepatic impairment, no dose adjustment is required. In patients with severe hepatic impairment, the dose should not exceed 20 mg / day.

Elderly people do not need to adjust the dosage regimen.

Overdose

Currently, no cases of overdose have been described. A single dose of 80 mg of esomeprazole did not cause any negative consequences.

Treatment: if necessary, carry out symptomatic and supportive therapy. The specific antidote is unknown. Dialysis is ineffective because esomeprazole binds to plasma proteins.

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

Pellets and pellets

Storage conditions

At temperatures below 30 °C.

Shelf life

2 years

Active ingredient

Esomeprazole

Conditions of release from pharmacies

By prescription

Dosage form

granules

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, Gastric and Duodenal ulcers, Reflux Esophagitis