Nexium film-coated tablets 40 mg blister No. 14

Instructions Nexium film-coated tablets 40 mg blister No. 14

Composition

active ingredient: esomeprazole;

1 film-coated tablet contains esomeprazole magnesium trihydrate, equivalent to 40 mg of esomeprazole;

excipients: glycerol monostearate, hydroxypropylcellulose, hypromellose, magnesium stearate, methacrylate copolymer (type A), microcrystalline cellulose, synthetic paraffin, macrogol, polysorbate 80, crospovidone, sodium stearyl fumarate, spherical sugar, talc, titanium dioxide (E 171), triethyl citrate, dyes: for 40 mg tablets: reddish-brown iron oxide (E 172).

Dosage form

Film-coated tablets.

Main physicochemical properties: 40 mg tablet: pink, oval, biconvex, film-coated tablet with imprint 40 mG on one side and "A/EI" on the other side.

Pharmacotherapeutic group

Drugs for the treatment of peptic ulcer and gastroesophageal reflux disease. Proton pump inhibitors. ATC code A02B C05.

Pharmacological properties

Pharmacodynamics

Esomeprazole is the S-isomer of omeprazole, which reduces gastric acid secretion by a specific, targeted mechanism of action. It is a specific inhibitor of the parietal cell proton pump. Both the R- and S-isomers of omeprazole exhibit similar pharmacodynamic activity.

Mechanism of action

Esomeprazole is a weak base that concentrates and converts to the active form in the highly acidic environment of the secretory tubules of parietal cells, where it inhibits the enzyme H+K+-ATPase – the proton pump – and suppresses both basal and stimulated acid secretion.

Pharmacodynamic effects

After oral administration of 20 and 40 mg of esomeprazole, the onset of action of the drug is observed within one hour.

After repeated administration of 20 mg esomeprazole once daily for five days, on the fifth day the mean maximal acid secretion after pentagastrin stimulation is reduced by 90% when measured 6-7 hours after taking the drug.

After five days of oral administration of esomeprazole 20 mg and 40 mg in patients with symptomatic GERD, intragastric pH above 4 was maintained for an average of 13 and 17 hours, respectively, over a 24-hour period. The proportion of patients in whom gastric pH above 4 was maintained for 8, 12 and 16 hours after administration of esomeprazole 20 mg was 76%, 54% and 24%, respectively. The corresponding proportions of patients receiving esomeprazole 40 mg were 97%, 92% and 56%.

Using AUC as a proxy for plasma drug concentration, a relationship between acid secretion inhibition and post-drug exposure was demonstrated.

When using esomeprazole at a dose of 40 mg, approximately 78% of patients with reflux esophagitis recover after four weeks, and 93% after eight weeks of treatment.

After one week of esomeprazole 20 mg twice daily with appropriate antibiotics, approximately 90% of patients experience successful eradication of H. pylori.

After eradication within one week, there is no need for further monotherapy with antisecretory drugs for effective ulcer treatment and symptom relief in patients with uncomplicated duodenal ulcers.

In a randomized, double-blind, placebo-controlled clinical trial, patients with endoscopically proven bleeding peptic ulcer class Ia, Ib, IIa or IIb (9%, 43%, 38% and 10% respectively) according to Forrest were randomized to receive Nexium, solution for infusion (n = 375) or placebo (n = 389). After endoscopic hemostasis, patients received either esomeprazole 80 mg as an intravenous infusion over 30 minutes followed by a continuous infusion at a rate of 8 mg/hour or placebo for 72 hours. After the initial 72-hour period, all patients were switched to open-label oral Nexium 40 mg for 27 days for acid suppression. The 3-day rebleeding rate was 5.9% in the Nexium group and 10.3% in the placebo group. At 30 days post-treatment, the rebleeding rate was 7.7% in the Nexium and placebo groups, respectively.

During treatment with antisecretory drugs, serum gastrin levels increase in response to decreased acid secretion. Chromogranin A (CgA) levels also increase due to decreased gastric acidity. Laboratory tests for neuroendocrine tumors may be affected by elevated CgA levels. According to published data, proton pump inhibitor therapy should be discontinued at least 5 days before CgA measurement. If CgA and gastrin levels have not returned to normal within 5 days of discontinuation of esomeprazole therapy, repeat measurements should be performed 14 days after discontinuation.

A slight increase in the frequency of gastric glandular cysts has been observed in patients treated with antisecretory drugs for a long time. These changes are a physiological consequence of the pronounced inhibition of gastric secretion; they are benign in nature and disappear after the end of treatment.

Decreased gastric acidity from any cause, including proton pump inhibitors, leads to an increase in the number of bacteria normally present in the gastrointestinal tract in the stomach. Treatment with proton pump inhibitors may slightly increase the risk of gastrointestinal infections caused by, for example, Salmonella and Campylobacter, and in hospitalized patients, possibly also Clostridium difficile.

Clinical efficacy

Two studies with ranitidine as an active comparator showed superior efficacy of Nexium in the treatment of gastric ulcers in patients taking NSAIDs, including cyclooxygenase-2 (COX-2) selective NSAIDs.

Two placebo-controlled studies demonstrated superior efficacy of Nexium in the prevention of gastric and duodenal ulcers in patients (aged > 60 years and/or with pre-existing ulcers) taking NSAIDs, including COX-2 selective NSAIDs.

Pediatric population

In a study of pediatric patients with GERD (aged < 1 to 17 years) receiving long-term treatment with proton pump inhibitors (PPIs), 61% of children had mild ECL cell hyperplasia of unknown clinical significance; no atrophic gastritis or carcinoid tumors were observed.

Pharmacokinetics

Absorption

Esomeprazole is unstable in an acidic environment, so enteric-coated granules are used for oral administration. Under in vivo conditions, only a small part of esomeprazole is converted to the R-isomer. The drug is rapidly absorbed: the maximum concentration in the blood plasma is reached 1-2 hours after administration. The absolute bioavailability of esomeprazole after a single dose of 40 mg is 64% and increases to 89% against the background of daily administration once a day. For a dose of 20 mg of esomeprazole, these figures are 50% and 68%, respectively. Food intake slows down and reduces the absorption of esomeprazole, but this does not significantly affect the effect of esomeprazole on intragastric acidity.

Distribution

The apparent volume of distribution at steady state in healthy volunteers is approximately 0.22 l/kg body weight. Esomeprazole is 97% bound to plasma proteins.

Biotransformation

Esomeprazole is completely metabolised by the cytochrome P450 (CYP) system. The main part of the metabolism of esomeprazole depends on the polymorphic isoform CYP2C19, which is responsible for the formation of the hydroxy- and desmethyl metabolites of esomeprazole. The remaining part is metabolised by another specific isoform, CYP3A4, which is responsible for the formation of esomeprazole sulfone, the main metabolite found in plasma.

Breeding

The parameters listed below reflect mainly the pharmacokinetics in patients with an active CYP2C19 enzyme (extensive metabolizers).

Total plasma clearance is approximately 17 l/h after a single dose and approximately 9 l/h after multiple doses. The plasma elimination half-life is approximately 1.3 hours with once-daily dosing. Esomeprazole is completely eliminated from plasma between doses and there is no tendency for accumulation in the body with once-daily dosing.

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

Linearity/nonlinearity

The pharmacokinetics of esomeprazole have been studied in doses up to 40 mg twice daily. The area under the plasma concentration-time curve increases with repeated administration of esomeprazole. This increase is dose-dependent and results in a non-linear increase in dose-AUC after repeated administration. This time- and dose-dependent effect is due to a decrease in first-pass metabolism and systemic clearance, possibly due to inhibition of the CYP2C19 enzyme by esomeprazole and/or its sulphone metabolite.

Patients of special groups

Slow metabolizers

Approximately 2.9 ± 1.5% of the population lack a functional CYP2C19 enzyme and are referred to as poor metabolisers. In these individuals, the metabolism of esomeprazole is likely to be catalysed predominantly by CYP3A4. After multiple doses of esomeprazole 40 mg once daily, the mean area under the plasma concentration-time curve was approximately 100% higher in poor metabolisers than in subjects with a functional CYP2C19 enzyme (extensive metabolisers). The mean maximum plasma concentration was increased by approximately 60%. These findings do not require any changes in the dosage of esomeprazole.

Sex

Liver dysfunction

The metabolism of esomeprazole in patients with mild or moderate hepatic impairment may be impaired. In patients with severe hepatic impairment, the metabolic rate is reduced, resulting in a doubling of the area under the plasma concentration curve of esomeprazole over time. Therefore, the maximum dose of the drug in patients with severe hepatic impairment should not exceed 20 mg. Esomeprazole or its major metabolites do not show a tendency to accumulate when administered once daily.

Kidney dysfunction

No studies have been conducted in patients with reduced renal function. Since the kidneys are responsible for the excretion of esomeprazole metabolites, but not the parent compound, no changes in the metabolism of esomeprazole are expected in patients with impaired renal function.

Elderly patients

The metabolism of esomeprazole is slightly altered in elderly patients (71-80 years).

Pediatric population

Children aged 12-18 years

After repeated administration of esomeprazole at a dose of 20 mg and 40 mg, the total exposure (AUC) and time to maximum plasma concentration (tmax) in children aged 12-18 years were similar to the AUC and tmax values in adults when using both doses of esomeprazole.

Indication

Adults

Gastroesophageal reflux disease (GERD):

treatment of erosive reflux esophagitis; long-term treatment of patients with cured esophagitis to prevent relapse; symptomatic treatment of gastroesophageal reflux disease (GERD).

In combination with appropriate antibacterial therapeutic agents for the eradication of Helicobacter pylori:

Treatment of duodenal ulcers caused by Helicobacter pylori; prevention of recurrence of peptic ulcers in patients with ulcers caused by Helicobacter pylori.

Patients requiring long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs):

Healing of gastric ulcers caused by the use of NSAIDs; Prevention of gastric and duodenal ulcers caused by the use of NSAIDs in patients at risk.

Long-term treatment after intravenous administration of the drug for the prevention of recurrent bleeding from peptic ulcers.

Treatment of Zollinger-Ellison syndrome.

Children aged 12 and over:

Gastroesophageal reflux disease (GERD):

treatment of erosive reflux esophagitis; long-term treatment of patients with cured esophagitis to prevent relapse; symptomatic treatment of gastroesophageal reflux disease (GERD).

In combination with antibiotics in the treatment of duodenal ulcers caused by Helicobacter pylori.

Contraindication

Hypersensitivity to the active substance, substituted benzimidazoles or to any of the excipients.

Esomeprazole should not be used concomitantly with nelfinavir (see section “Interaction with other medicinal products and other types of interactions”).

Interaction with other medicinal products and other types of interactions

Protease inhibitors

Interactions of omeprazole with some protease inhibitors have been reported. The clinical significance and mechanisms of these reported interactions are not always known. Increased gastric pH during treatment with omeprazole may alter the absorption of protease inhibitors. Another possible mechanism of interaction is inhibition of CYP2C19 activity.

It has been reported that serum levels of atazanavir and nelfinavir were decreased when co-administered with omeprazole, and their concomitant use is not recommended. Co-administration of omeprazole (40 mg once daily) with atazanavir 300 mg/ritonavir 100 mg in healthy volunteers significantly decreased atazanavir exposure (AUC, Cmax, and Cmin values decreased by approximately 75%). Increasing the atazanavir dose to 400 mg did not compensate for the effect of omeprazole on atazanavir exposure. Co-administration of omeprazole (20 mg daily) with atazanavir 400 mg/ritonavir 100 mg in healthy volunteers resulted in an approximately 30% decrease in atazanavir exposure compared to the exposure observed with daily administration of 300 mg atazanavir/100 mg ritonavir without omeprazole 20 mg daily. Co-administration of omeprazole (40 mg daily) resulted in a 36-39% decrease in mean nelfinavir AUC, Cmax and Cmin, and a 75-92% decrease in mean AUC, Cmax and Cmin of the pharmacologically active metabolite M8. Due to the similarity of pharmacodynamic effects and pharmacokinetic properties of omeprazole and esomeprazole, concomitant use of esomeprazole with atazanavir is not recommended (see section 4.4); Concomitant use of esomeprazole with nelfinavir is contraindicated (see section "Contraindications").

During concomitant therapy with omeprazole (40 mg daily), serum levels of saquinavir (co-administered with ritonavir) were reported to increase (80-100%). Treatment with omeprazole 20 mg daily had no effect on the exposure of darunavir (co-administered with ritonavir) and amprenavir (co-administered with ritonavir). Treatment with esomeprazole 20 mg daily had no effect on the exposure of amprenavir (co-administered with or without ritonavir). Treatment with omeprazole 40 mg daily had no effect on the exposure of lopinavir (co-administered with ritonavir).

Some patients have experienced increased methotrexate levels when co-administered with proton pump inhibitors.

When prescribing high doses of methotrexate, temporary withdrawal of esomeprazole should be considered.

Tacrolimus

Increased serum tacrolimus levels have been reported with concomitant use of esomeprazole. Increased monitoring of tacrolimus concentrations and renal function (creatinine clearance) is required; tacrolimus dosage should be adjusted if necessary.

Drugs whose absorption depends on pH

The suppression of gastric acidity during treatment with esomeprazole and other PPIs may reduce or increase the absorption of drugs whose absorption depends on gastric pH. As with other drugs that reduce gastric acidity, the absorption of drugs such as ketoconazole, itraconazole and erlotinib may be reduced, while the absorption of drugs such as digoxin may be increased during treatment with esomeprazole. Concomitant use of omeprazole (20 mg daily) and digoxin in healthy volunteers increased the bioavailability of digoxin by 10% (in two out of ten subjects - up to 30%). Rare cases of digoxin-induced toxicity have been reported. However, caution should be exercised when prescribing high doses of esomeprazole to elderly patients. Therapeutic drug monitoring of digoxin should be intensified.

Medicinal products metabolized by CYP2C9

Esomeprazole is an inhibitor of CYP2C19, the main enzyme that metabolizes esomeprazole. Accordingly, when esomeprazole is combined with drugs that are metabolized by CYP2C19, such as diazepam, citalopram, imipramine, clomipramine, phenytoin, etc., the plasma concentrations of these drugs may increase and a dose reduction may be necessary. This should be taken into account in particular when esomeprazole is prescribed for "on-demand" use.

Diazepam

Concomitant use of esomeprazole at a dose of 30 mg resulted in a 45% decrease in the clearance of diazepam, a CYP2C19 substrate.

Phenytoin

When concomitantly administered with esomeprazole at a dose of 40 mg in patients with epilepsy, an increase in the minimum plasma concentration of phenytoin by 13% was observed. It is recommended to monitor the level of phenytoin in the blood plasma at the beginning of therapy with esomeprazole or in case of its cancellation.

Voriconazole

Administration of omeprazole (40 mg once daily) increased the Cmax and AUCτ of voriconazole (a CYP2C19 substrate) by 15% and 41%, respectively.

Cilostazol

Omeprazole and esomeprazole act as inhibitors of CYP2C19. In a cross-over study, administration of omeprazole at a dose of 40 mg to healthy volunteers increased the Cmax and AUC of cilostazol by 18% and 26%, respectively, and one of its active metabolites by 29% and 69%, respectively.

Cisapride

In healthy volunteers, when co-administered with esomeprazole (40 mg), the area under the plasma concentration-time curve (AUC) of cisapride increased by 32% and the elimination half-life (t½) increased by 31%, but no significant increase in maximum plasma levels of cisapride was observed. The slight prolongation of the QTc interval observed with cisapride monotherapy was not observed with co-administration of cisapride with esomeprazole (see also section "Special warnings and precautions for use").

Warfarin

In a clinical study, it was shown that concomitant use of esomeprazole 40 mg in patients on warfarin therapy maintained coagulation times within acceptable limits. However, in the post-marketing period, a few isolated cases of clinically significant increases in the international normalized ratio (INR) have been reported during concomitant use of these drugs. Monitoring is recommended at the beginning and after the end of concomitant use of esomeprazole with warfarin or other coumarin derivatives.

Clopidogrel

The results of the pharmacokinetic (PK)/pharmacodynamic (PD) interaction between clopidogrel (loading dose 300 mg/maintenance dose 75 mg/day) and esomeprazole (oral 40 mg/day) obtained during studies in healthy volunteers showed a decrease in the exposure of the active metabolite of clopidogrel by an average of 40% and a decrease in the maximum inhibition rate (induced by ADP) of platelet aggregation by an average of 14%.

In a study in healthy volunteers, when clopidogrel was used together with esomeprazole and acetylsalicylic acid (ASA) in a fixed dose combination (20 mg + 81 mg, respectively) compared to clopidogrel as monotherapy, a decrease in exposure to the active metabolite of clopidogrel by almost 40% was observed.

However, the maximum levels of inhibition of (ADP-induced) platelet aggregation in these individuals were the same in the clopidogrel monotherapy group and in the clopidogrel plus esomeprazole and ASA group.

Observational and clinical studies have provided conflicting data on the clinical aspects of the PK/PD interaction of esomeprazole with respect to major cardiovascular events. As a precautionary measure, concomitant use of esomeprazole and clopidogrel should be avoided.

Investigational medicinal products without clinically significant interactions

It was noted that esomeprazole had no clinically significant effect on the pharmacokinetics of amoxicillin or quinidine.

Naproxen or rofecoxib

No pharmacokinetic interactions were observed during short-term studies of concomitant use of esomeprazole with naproxen or rofecoxib.

Effect of other medicinal products on the pharmacokinetics of esomeprazole

Drugs that inhibit CYP2C19 and/or CYP3A4 activity

Esomeprazole is metabolised by CYP2C19 and CYP3A4. Co-administration of esomeprazole with the CYP3A4 inhibitor clarithromycin (500 mg twice daily) resulted in a doubling of esomeprazole exposure (AUC). Co-administration of esomeprazole with a combined CYP2C19 and CYP3A4 inhibitor may result in a more than two-fold increase in esomeprazole exposure. The CYP2C19 and CYP3A4 inhibitor voriconazole increased the AUCτ of omeprazole by 280%. Dose adjustment of esomeprazole is generally not required in any of these situations. However, dose adjustment should be considered in patients with severe hepatic impairment and if long-term treatment is indicated.

Drugs that induce CYP2C19 and/or CYP3A4 activity

Drugs known to induce the activity of CYP2C19 or CYP3A4 or both enzymes (such as rifampicin and St. John's wort) may lead to decreased serum levels of esomeprazole by increasing its rate of metabolism.

Pediatric population

Drug interaction studies have only been conducted in adults.

Application features

In the presence of any alarming symptoms (e.g. significant spontaneous weight loss, recurrent vomiting, dysphagia, haematemesis or melena), as well as in the presence or suspicion of gastric ulcer, malignancy should be excluded, as treatment with Nexium may lead to symptomatic relief and delay diagnosis.

Long-term use of the drug

Patients taking the drug for a long period (especially patients receiving treatment with the drug for more than a year) should be under regular medical supervision.

Treatment on demand

Patients taking Nexium as needed should be instructed to contact their physician if symptoms change.

Helicobacter pylori eradication

When prescribing esomeprazole for the eradication of Helicobacter pylori, the possibility of drug interactions between all components of the triple therapy should be taken into account. Clarithromycin is a potent inhibitor of CYP3A4, therefore, when prescribing triple therapy to patients receiving other drugs metabolized by CYP3A4 (e.g. cisapride), it is necessary to consider possible contraindications and interactions of clarithromycin with these drugs.

Gastrointestinal infections

The use of proton pump inhibitors may slightly increase the risk of developing gastrointestinal infections such as Salmonella and Campylobacter (see section "Pharmacodynamics").

Vitamin B12 absorption

Esomeprazole, like all drugs that block the action of hydrochloric acid, may reduce the absorption of vitamin B12 (cyanocobalamin) due to the development of hypo- or achlorhydria. This should be taken into account in the case of long-term treatment of patients with reduced vitamin B12 stores in the body or patients with risk factors for reduced vitamin B12 absorption.

Hypomagnesemia

Severe hypomagnesemia has been reported in patients treated with proton pump inhibitors (PPIs) such as esomeprazole for at least three months, and in most cases for a year. Serious manifestations of hypomagnesemia such as fatigue, tetany, delirium, seizures, dizziness, and ventricular arrhythmias may occur, but these symptoms may be insidious in onset and may be missed. In most cases, patients with hypomagnesemia improved after magnesium replacement therapy and discontinuation of PPI therapy.

For patients expected to be on long-term treatment, or for patients receiving PPI treatment concomitantly with digoxin or medicinal products that may cause hypomagnesaemia (e.g. diuretics), healthcare professionals should consider determining magnesium levels before initiating PPI treatment and periodically during therapy.

Risk of fractures

Proton pump inhibitors, especially at high doses and during long-term treatment (> 1 year), may slightly increase the risk of hip, wrist and spine fractures, mainly in elderly patients or in the presence of other risk factors. Observational data suggest that proton pump inhibitors may increase the overall risk of fractures by 10-40%. Some of these increased fractures may be associated with other risk factors. Patients at risk of osteoporosis should be treated according to current clinical guidelines and receive adequate vitamin D and calcium.

The concomitant use of esomeprazole with atazanavir is not recommended (see section 4.5). If the combination of atazanavir with a proton pump inhibitor cannot be avoided, close monitoring of patients in a hospital setting is recommended, and the dose of atazanavir should be increased to 400 mg with 100 mg ritonavir; the dose of esomeprazole should not exceed 20 mg.

Esomeprazole is an inhibitor of CYP2C19. Therefore, when initiating or ending treatment with esomeprazole, the possibility of interactions between esomeprazole and medicinal products metabolised by CYP2C19 should be considered. An interaction has been observed between clopidogrel and esomeprazole (see section 4.5). The clinical significance of this interaction remains uncertain. As a precautionary measure, concomitant use of esomeprazole and clopidogrel should be avoided.

When prescribing esomeprazole for use on an "as needed" basis, due to fluctuations in esomeprazole plasma concentrations, the consequences of drug interactions with other medicinal products should be taken into account, see section "Interaction with other medicinal products and other types of interactions".

Saccharose

This medicinal product contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Impact on laboratory test results

Due to increased levels of chromogranin A (CgA), laboratory tests for the detection of neuroendocrine tumours may be affected. To avoid this effect, treatment with esomeprazole should be discontinued at least 5 days before measuring CgA levels (see section 5.1).

Ability to influence reaction speed when driving vehicles or other mechanisms

Esomeprazole has minimal influence on the ability to drive and use machines. Adverse reactions such as dizziness (uncommon) and blurred vision (rare) have been reported (see section 4.8). If such disorders occur, patients should not drive or use machines.

Use during pregnancy or breastfeeding

There are currently no adequate data on the use of Nexium during pregnancy. A somewhat larger number of epidemiological studies of the use of the racemic mixture of omeprazole during pregnancy indicate the absence of congenital malformations and fetotoxic effects. Animal studies of esomeprazole have not revealed direct or indirect harmful effects on embryonal/fetal development. Animal studies of the racemic mixture have not revealed direct or indirect harmful effects on pregnancy, childbirth or postnatal development. The drug should be prescribed with caution to pregnant women.

A moderate amount of data on pregnant women (300 to 1000 pregnancy outcomes) indicate no malformative or foeto/neonatal toxicity of esomeprazole.

The results of animal studies indicate the absence of direct or indirect harmful effects of the drug on reproductive function due to its toxic effect.

Breast-feeding

It is not known whether esomeprazole is excreted in human milk. There is insufficient information on the effects of esomeprazole on newborns/infants. Esomeprazole should not be used during breast-feeding.

Fertility

Animal studies of the racemic mixture of omeprazole indicate no effect of omeprazole on fertility when administered orally.

Method of administration and doses

Adults

Gastroesophageal reflux disease (GERD)

Treatment of erosive reflux esophagitis

40 mg once daily for 4 weeks.

Patients with untreated esophagitis or persistent symptoms are recommended to use the drug for an additional 4 weeks.

Long-term treatment of patients with cured esophagitis to prevent relapse:

20 mg once daily.

Symptomatic treatment of gastroesophageal reflux disease (GERD)

The dose for patients without esophagitis is 20 mg once daily. If after 4 weeks of treatment the symptoms are not controlled, the patient should be reassessed. After symptoms have resolved, 20 mg once daily may be sufficient for continued control. If necessary, the drug can be switched to an “as needed” regimen, i.e. 20 mg once daily. The use of the drug “as needed” for continued control of symptoms is not recommended in patients at risk of developing gastric and duodenal ulcers who are taking NSAIDs.

In combination with appropriate antibacterial therapeutic agents for the eradication of Helicobacter pylori, as well as for

Treatment of duodenal ulcers caused by Helicobacter pylori and prevention of recurrence of peptic ulcers in patients with ulcers caused by Helicobacter pylori: 20 mg Nexium with 1 g amoxicillin and 500 mg clarithromycin twice daily for 7 days.

Treatment of gastric ulcers caused by the use of NSAIDs:

The usual dose is 20 mg once a day. The duration of treatment is 4-8 weeks.

Prevention of gastric and duodenal ulcers caused by the use of NSAIDs in patients at risk:

20 mg once daily.

Long-term treatment after intravenous administration of the drug for the prevention of recurrent bleeding from peptic ulcers:

40 mg once daily for 4 weeks following intravenous administration of the drug for the prevention of recurrent bleeding from peptic ulcers.

Treatment of Zollinger-Ellison syndrome

The recommended starting dose of Nexium is 40 mg twice daily. The dose is then titrated individually; treatment is continued for as long as clinically indicated. Based on available clinical data, control of the condition can be achieved in most patients with doses of 80 to 160 mg esomeprazole per day. If doses exceed 80 mg per day, the dose should be divided and administered twice daily.

Patients of special groups

Patients with impaired renal function

No dose adjustment is required in patients with impaired renal function. Due to limited experience in patients with severe renal impairment, caution should be exercised when treating such patients (see section 5.2).

Patients with impaired hepatic function

No dose adjustment is required in patients with mild to moderate hepatic impairment. The maximum dose of Nexium for patients with severe hepatic impairment should not exceed 20 mg (see Pharmacokinetics).

Elderly patients

Elderly patients do not need dose adjustment.

Pediatric population

Children aged 12 and over

Gastroesophageal reflux disease (GERD)

Treatment of erosive reflux esophagitis:

40 mg once daily for 4 weeks.

Patients with untreated esophagitis or persistent symptoms are recommended to use the drug for an additional 4 weeks.

Long-term treatment of patients with cured esophagitis to prevent relapse:

20 mg once daily.

Symptomatic treatment of gastroesophageal reflux disease (GERD)

The dose for patients without esophagitis is 20 mg once daily. If after 4 weeks of treatment the symptoms are not controlled, the patient should be re-evaluated. Once symptoms have resolved, further control may be achieved by increasing the dose to 20 mg once daily.

Treatment of duodenal ulcers caused by Helicobacter pylori

When choosing the appropriate combination therapy, official national, regional and local guidelines on bacterial resistance, duration of treatment (usually 7 days, but sometimes up to 14 days) and appropriate use of antibacterial agents should be taken into account. Treatment should be carried out under specialist supervision.

Dosage recommendations

Children under 12 years old

Nexium should not be used