Nexium pellets for intestinal digestion 10 mg pack No. 28 + gran d/susp price

pharmachologic effect

Esomeprazole is the S-isomer of omeprazole. It inhibits the production of gastric acid. Nexium is a specific inhibitor of the parietal cell acid pump.

The drug begins to act in the strong acidic environment of the secretory tubules of parietal cells. There it inhibits the acid pump and inhibits basal and stimulated acid secretion.

In patients with gastroesophageal reflux disease, 5 days after taking the drug at a dose of 20 or 40 mg, gastric pH levels above 4 persisted for an average of 13–17 hours in patients with symptomatic gastroesophageal reflux disease. The effect does not depend on the method of administration: intravenously or orally.

When taking Nexium 40 mg orally, approximately 78% of patients with reflux esophagitis recover within 4 weeks. Therapy with the drug at a dose of 20 mg 2 times a day together with antibiotics leads to the successful destruction of Helicobacter pylori in 90% of patients within a week.

During treatment with the drug, the level of gastrin and chromogranin increases due to a decrease in the acidity of gastric juice. With long-term treatment, an increase in the incidence of gastric glandular cysts was noted. These changes are a physiological consequence of the suppression of gastric juice secretion. They are benign and negotiable in nature.

Treatment with Nexium may increase the risk of gastrointestinal infections. This occurs as esomeprazole reduces the acidity of gastric juice, which increases the number of bacteria that normally exist in the gastrointestinal tract.

The effect of the drug occurs quickly. 40 mg tablets give effect within half an hour after administration. It continues throughout the day. Repeated use reduces gastric secretion.

Esomeprazole binds to plasma proteins. The half-life of the drug is 1.3 hours when using one tablet once a day. The active substance is completely eliminated between doses and does not accumulate in the blood plasma.

Nexium pellets and granules for the preparation of suspension 10 mg No. 28

A country

Sweden
The country of production may vary depending on the batch of goods. Please check with the operator for detailed information when confirming your order.

Active substance

Esomeprazole

Compound

1 package contains: esomeprazole magnesium trihydrate 11.1 mg.
Excipients: copolymer of methacrylic acid and ethyl acrylate (1:1) - 9.5 mg, talc - 8.4 mg, sucrose, spherical granules (sugar, spherical granules) (size 0.250-0.355 mm) - 7.4 mg, hyprolose - 32.2 mg, hypromellose - 1.7 mg, triethyl citrate - 0.95 mg, magnesium stearate - 0.65 mg, glycerol monostearate 40-55 - 0.48 mg, polysorbate 80 - 0.27 mg, dextrose - 2813 mg, crospovidone - 75 mg, xanthan gum - 75 mg, anhydrous citric acid - 4.9 mg, yellow iron oxide dye - 1.8 mg. Enteric-coated pellets and granules for the preparation of a suspension for oral administration are pale yellow in color, of various sizes (the bulk are finely ground granules and larger ones are pellets). Brownish granules may be present.

pharmachologic effect

Esomeprazole is the S-isomer of omeprazole and reduces gastric acid secretion by specifically inhibiting the proton pump in gastric parietal cells. The S- and R-isomers of omeprazole have similar pharmacodynamic activities. Mechanism of action Esomeprazole is a weak base that transforms into an 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, thereby inhibiting both basal and stimulated secretion of hydrochloric acid . Effect on the secretion of hydrochloric acid in the stomach The effect of esomeprazole develops within 1 hour after oral administration of 20 mg or 40 mg. 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 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 oral esomeprazole 20 mg or 40 mg, intragastric pH values above 4 were maintained for an average of 13 and 17 hours out of 24 hours. When taking esomeprazole at a dose of 20 mg per day, an 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 esomeprazole, this ratio is 97%, 92% and 56%, respectively. A correlation was found between the concentration of the drug in plasma and the inhibition of hydrochloric acid secretion (the AUC parameter (area under the concentration-time curve) was used to assess the concentration). The therapeutic effect achieved as a result of inhibition of hydrochloric acid secretion. When taking Nexium at a dose of 40 mg, reflux healing -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 one-week eradication course do not require subsequent monotherapy with drugs that reduce the secretion of gastric glands for healing of the ulcer and elimination of symptoms. The effectiveness of Nexium for bleeding from peptic ulcers was shown in a study of patients with bleeding from peptic ulcers, confirmed endoscopically . 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 the 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. Increased concentrations 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 testing CgA concentrations. If during this time the CgA concentration has not returned to normal, the study should be repeated. In children and adult patients receiving esomeprazole for a long time, there is an increase in the number of enterochromaffin-like cells, probably associated with an increase in plasma gastrin concentrations. This phenomenon has no clinical significance. Patients taking drugs that reduce the secretion of gastric glands for a long period of 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 that 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, in hospitalized patients, probably Clostridium difficile. In two comparative studies with ranitidine, Nexium was shown to be superior in healing gastric ulcers in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors. In two studies, Nexium showed high efficacy in the prevention of gastric and duodenal ulcers in patients receiving NSAIDs (age group over 60 years and/or with a history of peptic ulcers), including selective COX-2 inhibitors.

Indications for use

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 ulcers associated with Helicobacter pylori. Long-term acid suppression 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 taking NSAIDs; - prevention of gastric and duodenal ulcers associated with taking NSAIDs in patients at risk. Zollinger-Ellison syndrome or other conditions characterized by pathological hypersecretion of the gastric glands, including idiopathic hypersecretion.

Mode of application

Nexium® in the dosage form of enteric-coated pellets and granules for oral suspension is intended primarily for pediatric patients and persons with difficulty swallowing. Inside. To take 10 mg of Nexium®, pour the contents of one packet into a glass containing 15 ml of water. To take 20 mg of Nexium®, pour the contents of 2 packets into a glass containing 30 ml of water. To take 40 mg of Nexium®, pour the contents of 4 packets into a glass containing 60 ml of water. The contents of the glass should be stirred and waited a few minutes for a suspension to form. The suspension can be taken orally immediately or within 30 minutes after preparation, stirring again before use. Then you should again add 15 ml of water to the glass, stir the remainder and take it orally. Carbonated water should not be used. Pellets and granules must not be chewed or crushed. The suspension can be administered through a nasogastric tube. Instructions for preparing and administering the drug through a nasogastric tube are given in the section “Administering the drug through a nasogastric tube.” Children 1-11 years old with body weight > 10 kg GERD Treatment of erosive reflux esophagitis: for patients weighing more than 10 kg but less than 20 kg - 10 mg once a day for 8 weeks. For patients weighing 20 kg or more - 10 mg or 20 mg once a day for 8 weeks. Symptomatic treatment of GERD: 10 mg once a day for up to 8 weeks. The use of esomeprazole in doses greater than 1 mg/kg/day has not been studied. Adults and children over 12 years of age GERD 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, after the first course, healing of 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 GERD: 20 mg once daily for patients without esophagitis. If symptoms do not disappear after 4 weeks of treatment, the patient should be further examined. After eliminating the symptoms, you can switch to the “as needed” regimen of taking the drug, i.e. take Nexium® 20 mg once daily if symptoms return. For patients taking NSAIDs who are at risk of developing gastric or duodenal ulcers, treatment on an as-needed basis is not recommended. Adults Gastric and duodenal ulcers As part of combination therapy for eradication with Helicobacter pylori: - treatment of duodenal ulcers associated with Helicobacter pylori: Nexium® 20 mg, amoxicillin 1 g and clarithromycin 500 mg. All drugs are taken twice a day for 1 week. - prevention of relapse of peptic ulcers associated with Helicobacter pylori: Nexium® 20 mg, amoxicillin 1 g and clarithromycin 500 mg. All drugs are taken twice a day for 1 week. Long-term acid suppression 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) Nexium® 40 mg 1 time per 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 gastric ulcers associated with taking NSAIDs: Nexium® 20 mg or 40 mg once a day. The duration of treatment is 4-8 weeks. - prevention of gastric and duodenal ulcers associated with taking NSAIDs: Nexium® 20 mg or 40 mg once a day. Conditions associated with pathological hypersecretion of the 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 using the drug in doses of up to 120 mg 2 times a day. Children under 1 year of age or weighing less than 10 kg: Due to the lack of data on efficacy and safety, Nexium® should not be used in children under 1 year of age or weighing less than 10 kg. Renal failure: - no dose adjustment is required. However, experience with the use of Nexium® in patients with severe renal failure is limited; — in this regard, caution should be exercised when prescribing the drug to such patients (see section “Pharmacokinetics”). Liver failure: in case of mild to moderate liver failure, no dose adjustment is required. For patients with severe hepatic impairment, the maximum daily dose should not be exceeded - 10 mg for patients aged 1-11 years and 20 mg for patients over 12 years of age. Elderly patients: no dose adjustment is required. Administration of the drug through a nasogastric tube: 1. To administer 10 mg of Nexium®, pour the contents of one package into a glass containing 15 ml of water. 2. To administer 20 mg of Nexium®, pour the contents of 2 packets into a glass containing 30 ml of water. 3. To administer 40 mg of Nexium®, pour the contents of 4 packets into a glass containing 60 ml of water. 4. Stir the contents of the glass and wait a few minutes for a suspension to form. 5. Mix the suspension again and draw it into the syringe. 6. Administer the suspension immediately or within 30 minutes after preparation. 7. Draw another 15 ml (for a dose of 10 mg), or 30 ml (for a dose of 20 mg), or 60 ml (for a dose of 40 mg) of water into the syringe, shake the syringe and inject the remaining suspension into the nasogastric tube. Unused suspension should be destroyed.

Interaction

The effect of esomeprazole on the pharmacokinetics of other drugs. Reduced secretion of hydrochloric acid in the stomach during treatment with esomeprazole and other proton pump inhibitors can lead to a decrease or increase in the absorption of drugs, the absorption of which depends on the acidity of the environment. Like other drugs that reduce gastric acidity, treatment with esomeprazole may result in decreased absorption of ketoconazole, itraconazole and erlotinib, and increased absorption of drugs such as digoxin. Co-administration of omeprazole 20 mg once daily with digoxin increased 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 pH 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 certain antiretroviral drugs, such as atazanavir and nelfinavir, during omeprazole therapy, a decrease in their serum concentrations is observed. Therefore, their simultaneous use is not recommended. Co-administration of omeprazole (40 mg once daily) with atazanavir 300 mg/ritonavir 100 mg in healthy volunteers resulted in a significant decrease in the bioavailability of atazanavir (AUC, Cmax and Cmin decreased by approximately 75%). Increasing the atazanavir dose to 400 mg did not compensate for the effect of omeprazole on the bioavailability of atazanavir. With the simultaneous use of omeprazole and saquinavir, 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-administration 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 in the metabolism of which the CYP2C19 isoenzyme is involved, such as diazepam, citalopram, imipramine, clomipramine, phenytoin, etc., may lead to increased plasma concentrations of these drugs, which, in turn, may require dose reduction. This interaction is especially important to remember when using Nexium on an as-needed basis. When 30 mg of esomeprazole and diazepam, which is a substrate of the CYP2C19 isoenzyme, are taken together, a decrease in the clearance of diazepam by 45% is observed. The use of esomeprazole at a dose of 40 mg led to an increase in residual phenytoin concentrations in patients with epilepsy by 13%. In this regard, it is recommended to monitor plasma concentrations of phenytoin when starting treatment with esomeprazole and when discontinuing it. The use of omeprazole at a dose of 40 mg once daily led to an increase in the area under the concentration-time curve and Cmax of voriconazole (CYP2C19 isoenzyme substrate) by 15% and 41%, respectively. Co-administration of warfarin with 40 mg esomeprazole does not lead to a change in coagulation time in patients taking warfarin for a long time. However, several cases of clinically significant increases in the INR index (international normalized ratio) have been reported with the combined use of warfarin and esomeprazole. It is recommended to monitor the INR at the beginning and at the end of the combined use of esomeprazole and warfarin or other coumarin derivatives. According to the results of the studies, a pharmacokinetic/pharmacodynamic interaction was noted between clopidogrel (loading dose of 300 mg and maintenance dose of 75 mg/day) and esomeprazole (40 mg/day orally), which leads to a decrease in the exposure of the active metabolite of clopidogrel by an average of 40% and a decrease in 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 20 mg/day. concomitantly with therapy with clopidogrel and acetylsalicylic acid (ACK), and when analyzing the clinical outcomes of large randomized trials, there was no increase in the risk of cardiovascular complications 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 a clear answer about the presence or absence of an increased risk of thromboembolic cardiovascular complications during the combined use of clopidogrel and proton pump inhibitors. When clopidogrel was used together with a fixed combination of 20 mg esomeprazole and 81 mg ASA, exposure to the active metabolite of clopidogrel decreased by almost 40% compared with clopidogrel monotherapy, while the maximum levels of inhibition of ADP-induced platelet aggregation were the same, which is likely due to simultaneous administration ASA in low dose. The use of omeprazole at a dose of 40 mg led to an increase in Cmax and AUC (area under the concentration-time curve) of cilostazol by 18% and 26%, respectively; for one of the active metabolites of cilostazol, the increase was 29% and 69%, respectively. Co-administration of cisapride with 40 mg of esomeprazole leads to an increase in the pharmacokinetic parameters of cisapride in healthy volunteers: AUC by 32% and half-life by 31%, but the maximum plasma concentration of cisapride does not change significantly. The slight prolongation of the QT interval, which was observed with cisapride monotherapy, did not increase with the addition of Nexium (see section "Special Instructions"). With the simultaneous use of esomeprazole and tacrolimus, an increase in the concentration of tacrolimus in the blood serum was noted. In some patients, an increase in the concentration of methotrexate was observed during combined use with proton pump inhibitors. When using high doses of methotrexate, the possibility of temporary withdrawal of esomeprazole should be considered. Nexium does not cause clinically significant changes in the pharmacokinetics of amoxicillin and quinidine. Studies evaluating short-term co-administration 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. The combined use of esomeprazole with clarithromycin (500 mg 2 times a day), which inhibits the CYP3A4 isoenzyme, leads to an increase in the AUC value of esomeprazole by 2 times. Co-administration of esomeprazole and a combined inhibitor of CYP3A4 and CYP2C19 isoenzymes, for example, voriconazole, may lead to a more than 2-fold increase in the AUC value for esomeprazole. As a rule, in such cases no dose adjustment of esomeprazole is required. Dose adjustment of esomeprazole may be required in patients with severe liver dysfunction and with long-term use. Drugs that induce the isoenzymes CYP2C19 and CYP3A4, such as rifampicin and St. John's wort preparations, when used together with esomeprazole, may lead to a decrease in the concentration of esomeprazole in the blood plasma by accelerating the metabolism of esomeprazole.

Side effect

The following are side effects, independent of the dosage regimen, noted with the use of Nexium, both during clinical trials and in post-marketing studies. The frequency of side effects is given in the following gradation: very often (? 1/10); often (?1/100, From the skin and subcutaneous tissues Uncommon: dermatitis, itching, rash, urticaria; Rarely: alopecia, photosensitivity; Very rarely: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis. From the musculoskeletal and connective tissue: - rare: arthralgia, myalgia; - very rare: muscle weakness. From the nervous system - often - headache; - infrequently - dizziness, paresthesia, drowsiness; - rarely - taste disturbance. 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; - uncommon - 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 disease. From the genital organs and breast: very rarely - gynecomastia. From the blood and lymphatic system - rarely - leukopenia, thrombocytopenia; - very rarely - agranulocytosis, pancytopenia. From the immune system: rarely - hypersensitivity reactions (for example, fever, angioedema, anaphylactic reaction/anaphylactic shock). From the respiratory system, chest and mediastinal organs: rarely - bronchospasm. From the kidneys and urinary tract: very rarely - interstitial nephritis. From 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.

Contraindications

- hypersensitivity to esomeprazole, substituted benzimidazoles or other ingredients included in the drug;
- hereditary fructose intolerance, glucose-galactose malabsorption or sucrase-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 indications other than gastroesophageal reflux disease; - esomeprazole should not be taken together with atazanavir and nelfinavir (see section “Interaction with other drugs and other types of drug interactions”). With caution: severe renal failure (experience is limited). Use during pregnancy and breastfeeding Currently, there is not enough data on the use of Nexium during pregnancy. The results of epidemiological studies of omeprazole, which is a racemic mixture, showed the absence of fetotoxic effects or impaired fetal development. 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 during postnatal development. The drug should be prescribed to pregnant women only if the expected benefit to the mother outweighs the possible risk to the fetus. It is not known whether esomeprazole is excreted in breast milk, so Nexium should not be given during breastfeeding.

Overdose

To date, extremely rare cases of intentional overdose have been described. Oral administration of esomeprazole at a dose of 280 mg was accompanied by general weakness and gastrointestinal symptoms. A single dose of 80 mg of Nexium did not cause any negative effects. The antidote for esomeprazole is unknown. Esomeprazole binds well to plasma proteins, so dialysis is ineffective. In case of overdose, symptomatic and general supportive treatment should be provided.

special instructions

If any alarming symptoms are present (eg, significant spontaneous weight loss, repeated vomiting, dysphagia, hematemesis, or melena), or if a gastric ulcer is present (or if a gastric ulcer is suspected), malignancy should be excluded because Treatment with Nexium may lead to a smoothing of symptoms and delay diagnosis. In rare cases, in patients who took omeprazole for a long time, histological examination of biopsies of the mucous membrane of the gastric body revealed atrophic gastritis. Patients taking the drug for a long period (especially more than a year) should be under regular medical supervision. Patients taking Nexium "as needed" should be instructed to contact their physician if their symptoms change. Taking into account fluctuations in the concentration of esomeprazole in plasma when prescribing therapy “as needed”, the interaction of the drug with other drugs should be taken into account (see section “Interaction with other drugs and other types of drug interactions”). When prescribing Nexium for Helicobacter pylori eradication, the possibility of drug interactions for all components of triple therapy should be taken into account. Clarithromycin is a potent inhibitor of CYP3A4, therefore, when prescribing eradication therapy to patients receiving other drugs metabolized by CYP3A4 (for example, cisapride), possible contraindications and interactions of clarithromycin with these drugs must be taken into account. Nexium tablets contain sucrose, so they are contraindicated in patients with hereditary fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficiency. According to the study results, a pharmacokinetic/pharmacodynamic interaction was noted between clopidogrel (loading dose of 300 mg and 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 in maximum inhibition of ADP-induced platelet aggregation by an average of 14%. Therefore, the simultaneous use of esomeprazole and clopidogrel should be avoided (see section “Interaction with other drugs and other types of drug interactions”). Individual observational studies indicate that proton pump inhibitor therapy may modestly increase the risk of osteoporosis-related fractures, but other similar studies have not reported an increased risk. Randomized, double-blind, controlled clinical trials of omeprazole and esomeprazole, including two open-label studies of long-term therapy (more than 12 years), did not confirm the association of osteoporotic fractures with the use of proton pump inhibitors. Although a causal relationship between the use of omeprazole/esomeprazole and osteoporotic fractures has not been established, patients at risk of developing osteoporosis or osteoporotic fractures should be under appropriate clinical supervision. Effect on the ability to drive vehicles and operate machinery 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.

Dispensing conditions in pharmacies

On prescription

Indications for use

Nexium is indicated for adults in the following cases:

Gastroesophageal reflux disease in patients with severe reflux symptoms or esophagitis.
For the treatment of gastric ulcers associated with nonsteroidal anti-inflammatory drug therapy.
Prevention of gastric and duodenal ulcers associated with nonsteroidal anti-inflammatory drug therapy in patients at risk.
Short-term maintenance of hemostasis and prevention of rebleeding in patients after endoscopic treatment of acute bleeding due to treatment of gastric or duodenal ulcers.

For children over 12 years of age, tablets are prescribed for:

treatment of erosive reflux esophagitis;
maintenance treatment of erosive reflux esophagitis to prevent relapse;
symptomatic treatment of gastroesophageal reflux disease.

In combination therapy, the drug in dosages of 20 and 40 mg can be prescribed for the treatment of gastric and duodenal ulcers.

For children aged 1 to 18 years, the drug is prescribed for antisecretory therapy in cases where it is impossible to use the oral route. For example, for the treatment of gastroesophageal reflux disease in patients with erosive reflux esophagitis or severe reflux symptoms.

Contraindications

Glucose-galactose malabsorption, sucrase-isomaltase deficiency, hereditary fructose intolerance (tablets, oral suspension);
Combined use with nelfinavir and atazanavir;
Hypersensitivity to the components of the drug, as well as to substituted benzimidazoles.

Nexium should be used with caution in severe renal failure.

For children, depending on the dosage form, the drug is prescribed:

Suspension for oral administration: from 1 year (with a body weight of at least 10 kg) for the treatment of erosive esophagitis and symptomatic treatment of gastroesophageal reflux disease; from 12 years of age in the treatment of gastroesophageal reflux disease;
Tablets: from 12 years of age for the treatment of gastroesophageal reflux disease;
Injection solution: from 1 year of age for the treatment of gastroesophageal reflux disease.

During pregnancy, Nexium can be prescribed only after a doctor has assessed the balance between the benefits to the health of the mother and the risk to the fetus. If it is necessary to use the drug during lactation, breastfeeding should be interrupted.

Side effects

With oral or intravenous use of the drug at a dose of 20 and 40 mg, the following body reactions to esomeprazole were identified:

From the blood and lymphatic system - thrombocytopenia, leukopenia, pancytopenia, agranulocytosis.
From the respiratory system - bronchospasm.
From the immune system – fever, anaphylactic shock, angioedema.
Skin: rash, itching, dermatitis, urticaria, photosensitivity reactions, alopecia, toxic epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome.
From the nervous system - headache, drowsiness, dizziness, paresthesia, disturbance of taste.
From the mental side - insomnia, confusion, agitation, depression, hallucinations.
From the digestive system - abdominal pain, diarrhea, constipation, nausea, vomiting, flatulence, dry mouth, gastrointestinal candidiasis, stomatitis, microscopic colitis.
Metabolic: peripheral edema, hyponatremia.
From the organs of hearing, vision and balance - blurred vision, vertigo.
From the liver - increased levels of liver enzymes, hepatitis, encephalopathy, liver failure.
From the kidneys and urinary system - renal failure, interstitial nephritis.
From the reproductive system – gynecomastia.
From the skeleton and connective tissue - fractures of the spine, hip or wrist, myalgia, arthralgia, muscle weakness.

In rare cases, during treatment with Nexium, patients experience general malaise and increased sweating.

Reactions at the injection site were frequently observed. They appeared mainly in studies using high doses of the drug for 3 days. In a preclinical study of Nexium, no vascular irritation was observed, but minor tissue inflammation was observed at the subcutaneous injection site.

Compatibility with other drugs

Studies regarding the interaction of Nexium with other medications have been conducted only in adults. Caution should be exercised in concomitant therapy with other drugs in children. Before starting simultaneous treatment, you should definitely consult your doctor.

Drugs that are metabolized by CYP2C19

The active substance of Nexium inhibits CYP2C19. When consuming phenytoin, diazepam, citalopram, clomipramine and other drugs that are metabolized by CYP2C19, their plasma concentrations may increase. When combined therapy may require a reduction in their doses.

It is recommended to monitor the blood concentrations of such drugs when starting esomeprazole therapy and when stopping it.

Drugs whose absorption depends on pH

Treatment with esomeprazole and other proton pump inhibitors may inhibit gastric secretion. This can lead to increased or decreased absorption of drugs, the absorption of which depends on the pH level of gastric juice. In particular, the absorption of itraconazole, ketoconazole, and erlotinib may be weakened, and the absorption of digoxin may be enhanced. It is necessary to monitor the concentration of digoxin in the blood and be careful when using high doses of esomeprazole in elderly patients.

The clinical significance and interaction of Nexium with some protease inhibitors has not been established. Increasing the pH level of gastric juice may alter their absorption. Other interactions are possible through inhibition of CYP2C19.

Concomitant treatment with omeprazole and atazanavir or nelfinavir is not recommended. Decreases in serum levels of these drugs were observed.

Drug interactions

The 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 can lead to a decrease or increase in the absorption of drugs, the absorption of which depends on the acidity of the environment. Like other drugs that reduce gastric acidity, treatment with esomeprazole may result in decreased absorption of ketoconazole, itraconazole and erlotinib, as well as increased absorption of drugs such as digoxin. Co-administration of omeprazole 20 mg once daily and digoxin increases the bioavailability of digoxin by 10% (the bioavailability of digoxin increased by up to 30% in 20% of 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 pH 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 certain antiretroviral drugs, such as atazanavir and nelfinavir, during omeprazole therapy, a decrease in their serum concentrations is observed. Therefore, their simultaneous use is not recommended. Co-administration of omeprazole (40 mg once daily) with atazanavir 300 mg/ritonavir 100 mg in healthy volunteers resulted in a significant decrease in the bioavailability of atazanavir (AUC, Cmax and Cmin decreased by approximately 75%). Increasing the atazanavir dose to 400 mg did not compensate for the effect of omeprazole on the bioavailability of atazanavir.

With the simultaneous use of omeprazole and saquinavir, 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-administration 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 in the metabolism of which the CYP2C19 isoenzyme is involved, such as diazepam, citalopram, imipramine, clomipramine, phenytoin, etc., may lead to increased plasma concentrations of these drugs, which, in turn, may require dose reduction. This interaction is especially important to remember when using Nexium® in an as-needed regimen. When 30 mg of esomeprazole and diazepam, which is a substrate of the CYP2C19 isoenzyme, are taken together, a decrease in the clearance of diazepam by 45% is observed.

The use of esomeprazole at a dose of 40 mg led to an increase in residual phenytoin concentrations in patients with epilepsy by 13%. In this regard, it is recommended to monitor plasma concentrations of phenytoin when starting treatment with esomeprazole and when discontinuing it.

The use of omeprazole at a dose of 40 mg once daily led to an increase in the area under the concentration-time curve and Cmax of voriconazole (CYP2C19 isoenzyme substrate) by 15% and 41%, respectively.

Co-administration of warfarin with 40 mg esomeprazole does not lead to a change in 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 with the combined use of warfarin and esomeprazole. It is recommended to monitor the INR at the beginning and at the end of the combined use of esomeprazole and warfarin or other coumarin derivatives.

According to the results of the studies, a pharmacokinetic/pharmacodynamic interaction was noted between clopidogrel (loading dose of 300 mg and maintenance dose of 75 mg/day) and esomeprazole (40 mg/day orally), which leads to a decrease in the exposure of the active metabolite of clopidogrel by an average of 40% and a decrease in 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 20 mg/day. simultaneously with therapy with clopidogrel and acetylsalicylic acid (ASA), and when analyzing the clinical outcomes of large-scale randomized trials, there was no increase in the risk of cardiovascular complications 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 a clear answer about the presence or absence of an increased risk of thromboembolic cardiovascular complications during the combined use of clopidogrel and proton pump inhibitors.

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

Esomeprazole, like omeprazole, inhibits the CYP2C19 isoenzyme. Co-administration of cilostazol and 40 mg omeprazole leads to an increase in the pharmacokinetic parameters of cilostazol in healthy volunteers: Cmax and AUC by 18% and 26%, respectively. Similar parameters of one of the active metabolites of cilostazol increase by 29% and 69%, respectively.

Co-administration of cisapride with 40 mg of esomeprazole leads to 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 does not change significantly. The slight prolongation of the QT interval, which was observed with cisapride monotherapy, did not increase with the addition of Nexium® (see section "Special Instructions").

With the simultaneous use of esomeprazole and tacrolimus, an increase in the concentration of tacrolimus in the blood serum was noted.

In some patients, an increase in the concentration of methotrexate was observed during combined use with proton pump inhibitors. When using high doses of methotrexate, the possibility of temporary withdrawal of esomeprazole should be considered.

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

Studies evaluating short-term co-administration 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. The combined use of esomeprazole with clarithromycin (500 mg 2 times a day), which inhibits the CYP3A4 isoenzyme, leads to an increase in the AUC value of esomeprazole by 2 times. Co-administration of esomeprazole and a combined inhibitor of CYP3A4 and CYP2C19 isoenzymes, for example, voriconazole, may lead to a more than 2-fold increase in the AUC value for esomeprazole. As a rule, in such cases no dose adjustment of esomeprazole is required. Dose adjustment of esomeprazole may be required in patients with severe liver dysfunction and with long-term use. Long-term use of the drug is not indicated for children and adolescents under 12 years of age.

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

Use of the drug

Nexium is used for internal use.

Adults and children over 12 years of age with gastroesophageal reflux disease are prescribed the following doses of the drug:

treatment of erosive reflux esophagitis – 40 mg once a day for four weeks;
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.

The tablets should be swallowed whole with water. You can dissolve them in 100 ml of clean water. The use of other liquids for taking tablets is unacceptable - it may affect their absorption.

It is possible to administer the tablet using a probe. This method is used when it is impossible to take the medicine on your own. It is also possible to take the drug by intravenous injections and infusions.

It is necessary to visually inspect the reconstituted solution before using it and exclude the presence of particles and discoloration. Only a clear solution can be used.

The solution is intended for single use only. If not all of the contents of the bottle have been used, the remainder should be discarded.

To prepare a solution for injection, add 5 ml of 0.9% sodium chloride for intravenous use to a vial of esomeprazole 40 mg. The reconstituted solution should be clear and colorless or slightly yellowish.

To prepare a solution for infusion, you need to dissolve the contents of one bottle - 40 mg of esomeprazole in 0.9% sodium chloride in an amount of up to 100 ml.

For adults

For patients who cannot take the drug in tablet form, it can be administered parenterally at a dosage of 20–40 mg once daily. For patients with reflux esophagitis, 40 mg per day is recommended. People who are receiving symptomatic treatment for reflux disease can limit themselves to 20 mg once a day.

The usual dose for patients with gastric ulcers caused by the use of nonsteroidal anti-inflammatory drugs is 20 mg once daily. To prevent gastric and duodenal ulcers caused by NSAIDs, patients at risk are also prescribed 20 mg of Nexium once a day.

Typically, treatment with the drug by intravenous administration is short-term. Patients should be switched to tablets as quickly as possible.

After therapeutic endoscopy of acute bleeding of gastric or duodenal ulcers, 80 mg of Nexium is administered as a bolus infusion. Its duration is 30 minutes. After this, the medication is continued in the form of a long-term intravenous infusion at a rate of 8 mg per hour for 72 hours.

Therapy should be continued with oral agents that inhibit acid secretion.

Recommendations for injections:

dosage 40 - 5 ml of reconstituted solution is administered intravenously over at least 3 minutes;
dosage 20 - 2.5 ml of the reconstituted solution or half this amount is administered intravenously over a period of at least 3 minutes.

Recommendations for infusions:

dosage 40 – the reconstituted solution is administered as an intravenous infusion lasting 10-30 minutes;
dosage 20 – half of the reconstituted solution is administered intravenously for 10–30 minutes;
dosage 80 – the reconstituted solution is administered as a long-term intravenous infusion over 30 minutes;
8 mg/hour – the reconstituted solution is administered as a long-term intravenous infusion over 71.5 hours.

Unused solution must be discarded.

No dose adjustment is necessary for patients with impaired renal function and mild or moderate hepatic impairment. Patients with severe renal impairment should not exceed a dose of 20 mg of the drug.

No dose adjustment is necessary for elderly patients.

For children

Children from one to 18 years of age, when taking a pill is not possible, can use Nexium for injections and infusions. The drug is administered parenterally once a day.

For children aged 1 to 11 years, the dosage depends on body weight. For the treatment of erosive reflux esophagitis, a child weighing less than 20 kg is prescribed 10 mg of the drug once a day. If the weight is more than 20 kg - 10 or 20 mg once a day. For the symptomatic treatment of gastroesophageal reflux disease in children aged 1 to 11 years, 10 mg is prescribed once daily. In this case, the dosage does not depend on body weight.

For the treatment of erosive reflux esophagitis, children from 12 to 18 years old are prescribed 40 mg of the drug once a day. For the treatment of gastroesophageal reflux disease, 20 mg of Nexium is prescribed once a day.

Treatment with intravenous injections usually does not last long. Patients should be switched to taking pills as quickly as possible.

Directions for use as indicated in the instructions:

For injection:

a dose of 40 - 5 ml of the reconstituted solution is administered as an intravenous injection lasting at least 3 minutes.
a dose of 20 - 2.5 ml or half of the reconstituted solution is administered as an intravenous injection lasting at least 3 minutes.
a dose of 10 - 1.25 ml of the reconstituted solution is administered intravenously, the duration of administration should be at least 3 minutes.

For infusions:

40 mg – the reconstituted solution is administered as an intravenous infusion lasting 10–30 minutes.
20 mg – half of the reconstituted solution is administered as an intravenous infusion over 10–30 minutes.
10 mg – a quarter of the reconstituted solution is administered as an intravenous infusion lasting 10–30 minutes.

Unused solution is discarded.

Release form and composition

Nexium is available in the following dosage forms:

Enteric-coated pellets and granules for the preparation of oral suspension: pale yellow, brown granules may be found, of various sizes (3042.7 mg in triple laminated bags, 28 bags in a cardboard box);
Film-coated tablets: oblong, biconvex, white at the break with yellow splashes; 20 mg each - light pink, on one side there is an engraving in the form of a fraction “A/EN”, on the other - “20 mG”; 40 mg each - pink, on one side engraved in the form of a fraction “A/EI”, on the other - “40 mG” (7 pieces in blisters, 1, 2 or 4 blisters in a cardboard pack);
Lyophilisate for preparing a solution for intravenous administration: almost white or white compressed mass (in glass bottles of 5 ml, 10 bottles in paper racks, 1 rack in a cardboard box with first opening control).

1 package of pellets and granules includes:

Active ingredient: esomeprazole – 10 mg (in the form of esomeprazole magnesium trihydrate – 11.1 mg);
Auxiliary components: anhydrous citric acid – 4.9 mg; hyprolose – 32.2 mg; talc – 8.4 mg; copolymer (1:1) of ethyl acrylate and methacrylic acid – 9.5 mg; sugar, spherical granules (sucrose, spherical granules ranging in size from 0.25 to 0.355 mm) – 7.4 mg; hypromellose – 1.7 mg; dextrose – 2813 mg; Magnesium stearate – 0.65 mg; triethyl citrate – 0.95 mg; glycerol monostearate 40-55 – 0.48 mg; polysorbate 80 – 0.27 mg; xanthan gum – 75 mg; dye crospovidone – 75 mg; yellow iron oxide – 1.8 mg.

1 tablet contains:

Active ingredient: esomeprazole – 20 or 40 mg (in the form of esomeprazole magnesium trihydrate – 22.3 or 44.5 mg);
Auxiliary components (tablets of 20/40 mg, respectively): sodium stearyl fumarate – 0.57/0.81 mg; macrogol – 3/4.3 mg; Magnesium stearate – 1.2/1.7 mg; hyprolose – 8.1/11 mg; glyceryl monostearate 40-55 – 1.7/2.3 mg; microcrystalline cellulose – 273/389 mg; hypromellose – 17/26 mg; red dye iron oxide (E172) – 0.06/0.45 mg; yellow dye iron oxide (E172) – 0.02/0 mg; copolymer (1:1) of methacrylic and ethacrylic acid – 35/46 mg; paraffin – 0.2/0.3 mg; polysorbate 80 – 0.62/1.1 mg; triethyl citrate – 10/14 mg; crospovidone – 5.7/8.1 mg; sugar, spherical granules (sucrose, spherical granules ranging in size from 0.25 to 0.355 mm) – 28/30 mg; talc – 14/20 mg; titanium dioxide (E171) – 2.9/3.8 mg.

The composition of 1 bottle of lyophilisate for the preparation of an injection solution includes:

Active ingredient: esomeprazole – 40 mg (in the form of esomeprazole sodium – 42.5 mg);
Auxiliary components: disodium edetate dihydrate – 1.5 mg; sodium hydroxide – 0.2-1 mg.

Overdose

Information on intentional overdose is limited. In the case of oral administration of a dose of 280 mg, general weakness and manifestations from the gastrointestinal tract appeared. A single oral dose of 80 mg of esomeprazole and intravenous administration of 308 mg of esomeprazole for 24 days did not cause any consequences.

A specific antidote is unknown. In case of overdose, symptomatic treatment and supportive measures are required. The active substance of Nexium binds significantly to blood plasma proteins and is therefore poorly excreted by dialysis.

Use during pregnancy and breastfeeding

Information on the use of Nexium during pregnancy is limited. Animal studies have not found direct or indirect negative effects on fetal development.

Caution should be exercised when prescribing tablets and parenteral administration to pregnant women.

It is not known whether esomeprazole passes into breast milk. No studies have been conducted in women who are breastfeeding. Nexium should not be used while breastfeeding.

special instructions

Nexium may mask the symptoms of a malignant disease. If any alarming symptoms appear, for example: periodic vomiting, significant weight gain, melena, dysphagia, hematemesis, or if a gastric ulcer is suspected, it should be excluded.

Esomeprazole inhibits the absorption of vitamin B 12. This is due to the fact that the substance blocks acid secretion.

Patients prescribed long-term treatment with Nexium or who are taking proton pump inhibitors with digoxin or drugs that can cause hypomagnesemia should monitor magnesium levels. It is recommended to measure it before starting treatment and periodically throughout therapy.