Ezonexa enteric-coated tablets 40 mg blister No. 14

Instructions for Ezonex enteric-coated tablets 40 mg blister No. 14

Composition

active ingredient: esomeprazole;

1 tablet contains 43.5 mg of esomeprazole magnesium dihydrate, equivalent to 40 mg of esomeprazole;

excipients: methacrylate copolymer dispersion, talc, triethyl citrate, hypromellose, spherical sugar, magnesium stearate, hydroxypropyl cellulose, glycerol monostearate, polysorbate 80, microcrystalline cellulose, povidone, macrogol 6000, crospovidone, sodium stearyl fumarate; Opadry Pink 03B34285 (hypromellose, titanium dioxide (E171), macrogol 400, red iron oxide (E172), yellow iron oxide (E172)).

Dosage form

Enteric-coated tablets.

Main physicochemical properties: pink, biconvex, elliptical, film-coated tablets measuring (8.2 ± 0.5) mm × (17 ± 0.6) mm.

Pharmacotherapeutic group

Drugs for the treatment of peptic ulcer and gastroesophageal reflux disease. Proton pump inhibitors.

ATX code A02B C05.

Pharmacological properties

Pharmacodynamics

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

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

Pharmacodynamic effects.

After oral administration of 20 mg and 40 mg esomeprazole, the onset of action is within one hour. After repeated administration of 20 mg esomeprazole once daily for 5 days, the mean peak acid output after pentagastrin stimulation is reduced by 90% when measured 6–7 hours after the dose on day 5.

After 5 days of oral administration of 20 mg and 40 mg esomeprazole, gastric pH was >4 for a mean of 13 and 17 hours, respectively, and >24 hours in patients with symptomatic reflux esophagitis. The proportion of patients with gastric pH >4 for 8, 12, and 16 hours after 20 mg esomeprazole was 76%, 54%, and 24%, respectively. The corresponding proportions for 40 mg esomeprazole were 97%, 92%, and 56%.

When using AUC as an indirect indicator of plasma concentration, the dependence of acid secretion inhibition on drug exposure was demonstrated.

Treatment of reflux esophagitis with esomeprazole 40 mg was successful in approximately 70% of patients after 4 weeks of treatment and in 93% after 8 weeks of treatment.

Esomeprazole 20 mg twice daily for one week, together with appropriate antibiotics, resulted in successful eradication of Helicobacter pylori in approximately 90% of patients. After one week of such treatment, further monotherapy with antisecretory drugs was not required for successful ulcer healing and symptom resolution in uncomplicated duodenal ulcers.

During the period of use of antisecretory drugs, the concentration of gastrin in the blood plasma increases in response to a decrease in acid secretion.

The increase in the number of ECL cells may be related to the increase in plasma gastrin levels observed in some patients with long-term use of esomeprazole.

There have been several reports of an increased incidence of gastric granular cysts with long-term use of antisecretory drugs. These phenomena are a physiological consequence of prolonged inhibition of acid secretion and are benign and reversible.

The reduction in gastric acid secretion caused by any proton pump inhibitor increases the number of bacteria normally present in the gastrointestinal tract in the stomach. Treatment with proton pump inhibitors may increase the risk of gastrointestinal infections caused by, for example, Salmonella or Campylobacter.

Esomeprazole was more effective compared to ranitidine in treating gastric ulcers in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors.

Esomeprazole was effective in preventing gastric and duodenal ulcers in patients treated with NSAIDs (in patients aged 60 years and older and/or with a history of ulcer), including COX-2 selective NSAIDs.

Pharmacokinetics

Esomeprazole is acid-labile and is administered orally as enteric-coated granules. There is little conversion to the R-isomer in vivo. Absorption of esomeprazole is rapid, with peak plasma concentrations occurring approximately 1–2 hours after dosing. Absolute bioavailability is 64% after a single 40 mg dose and increases to 89% after repeated once-daily dosing. For a 20 mg dose of esomeprazole, the corresponding values are 50% and 68%. The volume of distribution in healthy volunteers at steady state is 0.22 l/kg body weight. Esomeprazole is 97% bound to plasma proteins.

Food intake slows down and reduces the absorption of esomeprazole, but does not affect the effect of esomeprazole on gastric acidity.

Esomeprazole is completely metabolized by the cytochrome P450 (CYP) system. The main part of the metabolism of esomeprazole depends on the polymorphic CYP2C19, which is responsible for the formation of the hydroxy- and desmethyl metabolites of esomeprazole. The rest is due to a second specific isoform, CYP3A4, which is responsible for the formation of esomeprazole sulfone, the main metabolite in blood plasma.

The parameters listed below mainly reflect pharmacokinetics in individuals with a functional CYP2C19 enzyme (extensive metabolizers).

Total plasma clearance is approximately 17 l/h after a single dose and approximately 9 l/h after repeated administration. The plasma elimination half-life is approximately 1.3 hours after repeated once-daily dosing. The pharmacokinetics of esomeprazole have been studied at 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 more than dose-proportional increase in AUC after repeated administration. This time- and dose-dependence is explained by a decrease in first-pass metabolism and systemic clearance associated with inhibition of the CYP2C19 enzyme by esomeprazole and/or its sulfmetabolite. Esomeprazole is completely eliminated from plasma between doses without a tendency for accumulation with once-daily dosing.

The main metabolites of esomeprazole do not affect gastric secretion. Approximately 80% of an oral dose of esomeprazole is excreted as metabolites in the urine, the remainder in the feces. Less than 1% of the parent drug is recovered in the urine.

Special patient groups

Approximately 2.9 ± 1.5% of the patient population is deficient in the CYP2C19 enzyme (referred to as poor metabolisers). In these individuals, esomeprazole is predominantly metabolised by CYP3A4. After repeated once-daily administration of 40 mg esomeprazole, the mean area under the plasma concentration-time curve in poor metabolisers is approximately 100% higher than in subjects with normal CYP2C19 function (extensive metabolisers). The mean peak plasma concentration is increased by approximately 60%. These findings have no impact on the dosage of esomeprazole.

The metabolism of esomeprazole does not undergo significant changes in elderly patients (71–80 years).

After a single dose of 40 mg esomeprazole, the mean area under the plasma concentration-time curve was 30% higher in women than in men. No gender-related differences were observed with repeated once-daily dosing. These findings do not impact the dosing of esomeprazole.

Patients with hepatic/renal impairment

The metabolism of esomeprazole in patients with mild to moderate hepatic dysfunction may be impaired. The rate of metabolism is reduced in patients with severe hepatic impairment, resulting in a 2-fold increase in the area under the plasma concentration-time curve. Therefore, the maximum dose for patients with severe hepatic impairment is 20 mg. Esomeprazole and its metabolites do not tend to accumulate when administered once daily.

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

Elderly patients

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

Use in pediatrics

Children aged 12-18 years: After multiple doses of 20 mg and 40 mg esomeprazole, the overall exposure and time to peak plasma concentrations were similar to those in adults.

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 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.

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

Contraindication

Known hypersensitivity to esomeprazole, substituted benzimidazoles or other components of the drug.

Children's age (up to 12 years old).

Interaction with other medicinal products and other types of interactions

Effect of esomeprazole on the pharmacokinetics of other drugs

Protease inhibitors

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

Atazanavir and nelfinavir serum concentrations were decreased when co-administered with omeprazole, and their concomitant use is not recommended. Atazanavir exposure was significantly decreased (AUC, Cmax, and Cmin values decreased by approximately 75%) when omeprazole (40 mg once daily) was co-administered with atazanavir 300 mg/ritonavir 100 mg in healthy volunteers. Increasing the atazanavir dose to 400 mg did not compensate for the effect of omeprazole on atazanavir exposure. Atazanavir exposure was decreased by approximately 30% when omeprazole (20 mg daily) was co-administered with atazanavir 400 mg/ritonavir 100 mg in healthy volunteers compared to the exposure of 300 mg atazanavir/100 mg ritonavir daily without omeprazole 20 mg daily. Concomitant use 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 nelfinavir AUC, Cmax and Cmin of the pharmacologically active metabolite M8. Due to the similarity of pharmacodynamic effects and pharmacokinetic properties of omeprazole and esomeprazole, esomeprazole should not be used concomitantly with atazanavir (see section 4.4); concomitant use of esomeprazole with nelfinavir is contraindicated (see section 4.3).

In cases of concomitant therapy with omeprazole (40 mg daily), it has been reported that the serum levels of saquinavir (in combination with ritonavir) increased (80-100%). Treatment with omeprazole 20 mg daily had no effect on the exposure of darunavir (in combination with ritonavir) and amprenavir (in combination with ritonavir). Treatment with esomeprazole 20 mg daily had no effect on the exposure of amprenavir (in combination with or without ritonavir). Treatment with omeprazole 40 mg daily had no effect on the exposure of lopinavir (in combination with ritonavir).

Methotrexate

Some patients have experienced increased methotrexate levels when given concomitantly 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. Serum tacrolimus concentrations and renal function (creatinine clearance) should be closely monitored and the tacrolimus dosage adjusted if necessary.

Drugs whose absorption depends on pH

The suppression of gastric acidity during treatment with proton pump inhibitors, including esomeprazole, may affect the absorption of drugs whose absorption depends on gastric pH. As with other drugs that reduce intragastric acidity, the absorption of drugs such as ketoconazole, itraconazole and erlotinib may be reduced during treatment with esomeprazole, while the absorption of drugs such as digoxin may be increased. 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%). Digoxin-related toxicity has been reported rarely. However, caution should be exercised when prescribing high doses of esomeprazole to elderly patients. Medical monitoring of digoxin should be increased.

Medicinal products metabolized by CYP2C9

Esomeprazole is an inhibitor of CYP2C19, the main enzyme that metabolizes esomeprazole. Accordingly, when esomeprazole is combined with drugs metabolized by CYP2C19, such as diazepam, citalopram, imipramine, clomipramine, phenytoin, etc., the plasma concentrations of these drugs may increase, which may require a reduction in their dose. This should be considered in particular when esomeprazole is prescribed for "as needed" use.

Diazepam

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

Phenytoin

When phenytoin and esomeprazole 40 mg were co-administered in patients with epilepsy, a 13% increase in phenytoin trough plasma concentrations was observed. It is recommended that phenytoin plasma levels be monitored at the start of esomeprazole therapy and upon discontinuation.

Voriconazole

Concomitant use 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 of omeprazole 40 mg and cilostazol in healthy volunteers, an increase in Cmax and AUC of cilostazol by 18% and 26%, respectively, and of one of its active metabolites by 29% and 69%, respectively, was observed.

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 alone was not observed with co-administration of cisapride with esomeprazole (see also section 4.4).

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 with concomitant use of these drugs. Monitoring is recommended at the beginning and end of combined therapy with esomeprazole and 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 in studies involving 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, co-administration of clopidogrel with esomeprazole and acetylsalicylic acid (ASA) in a fixed dose combination (20 mg + 81 mg, respectively) resulted in an almost 40% reduction in exposure to the active metabolite of clopidogrel compared to clopidogrel alone.

However, the maximum levels of inhibition of (ADP-induced) platelet aggregation 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, the concomitant use of esomeprazole and clopidogrel should be avoided.

Investigational medicinal products without clinically significant interactions

Amoxicillin and quinidine

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, except in patients with severe hepatic impairment and when long-term treatment is indicated.

Drugs that induce CYP2C19 and/or CYP3A4 activity

Drugs that 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 alarming symptoms (e.g., significant weight loss, recurrent nausea, dysphagia, hematemesis, or melena) and in cases where gastric ulcer is suspected or present, malignancy should be excluded, as the use of Ezonexa® may alter symptoms and delay the determination of the correct diagnosis.

Patients who use the drug for a long time (especially those who take it for more than a year) should be under regular supervision.

Patients taking the drug on an “as needed” basis should inform their doctor if their symptoms change. When prescribing esomeprazole for the eradication of Helicobacter pylori, it is necessary to take into account the possible drug interactions of all components of the triple therapy. Clarithromycin is a potent CYP3A4 inhibitor, therefore its contraindications and interactions should be considered (when using triple therapy with esomeprazole and drugs that are metabolized by CYP3A4, such as cisapride).

The use of proton pump inhibitors may slightly increase the risk of gastrointestinal infections such as Salmonella and Campylobacter.

Esomeprazole, like all drugs that block the production of hydrochloric acid, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be taken into account in patients with reduced vitamin B12 levels and who are at risk of reduced vitamin B12 absorption with prolonged use.

Severe hypomagnesemia has been reported in patients treated with proton pump inhibitors (PPIs) such as esomeprazole for at least 3 months and in most cases for 1 year. Serious manifestations of hypomagnesemia, such as tetany, delirium, seizures, dizziness, ventricular arrhythmias and fatigue, may have an abrupt or insidious onset. In most patients with hypomagnesemia, magnesium replacement therapy and discontinuation of the PPI have been successful.

In patients who are on long-term treatment or who are receiving concomitant therapy with digoxin or drugs that can cause hypomagnesemia (e.g., diuretics) with PPIs, physicians should monitor magnesium levels before initiating PPI therapy and periodically during treatment.

Risk of fractures

Proton pump inhibitors, especially at high doses and for long periods (> 1 year), may slightly increase the risk of hip, wrist, and spine fractures, mainly in the elderly or in the presence of other identified risk factors. Observational studies suggest that proton pump inhibitors may increase the overall risk of fractures by 10–40%. This increase may often be associated with other risk factors. Patients at risk of osteoporosis should be treated according to current clinical guidelines and should receive adequate vitamin D and calcium intake.

Subacute cutaneous lupus erythematosus (SCL)

The use of proton pump inhibitors has been associated with very rare cases of PsA. In the event of skin rashes, especially in areas exposed to sunlight, and joint pain, the patient should seek immediate medical attention. The doctor should consider discontinuing Ezonexa®. The occurrence of PsA during treatment with proton pump inhibitors in the past significantly increases the risk of PsA with subsequent treatment with other proton pump inhibitors.

Combination with other drugs.

Concomitant use of esomeprazole and atazanavir is not recommended. If the combination of atazanavir with proton pump inhibitors cannot be avoided, close monitoring of patients in a hospital setting is recommended, as well as an increase in the dose of atazanavir to 400 mg with 100 mg ritonavir; the dose of esomeprazole should not exceed 20 mg.

Esomeprazole is an inhibitor of CYP2C19. The potential for interactions with medicinal products metabolised by CYP2C19 should be considered before starting or immediately after stopping esomeprazole. An interaction has been observed between clopidogrel and esomeprazole (see section 4.5). The clinical significance of this interaction has not been established. As a precautionary measure, the concomitant use of esomeprazole and clopidogrel should be avoided unless clearly necessary.

When prescribing esomeprazole on an “as needed” basis, it is necessary to take into account fluctuations in esomeprazole concentrations due to interactions with other pharmaceuticals (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 medicinal product.

Impact on laboratory test results

Elevated chromogranin A (CgA) levels may interfere with the results of neuroendocrine tumour tests. To prevent this interference, esomeprazole treatment should be discontinued at least 5 days before CgA tests.

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

Pregnancy

There are currently no adequate data on the use of the drug during pregnancy. The somewhat larger amount of data on the use of the racemic mixture of omeprazole during pregnancy indicates the absence of an effect on the occurrence of birth defects 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 effects on the course of pregnancy, childbirth and 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 effects.

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

Ezonex® tablets should be swallowed whole with sufficient liquid. The tablets should not be chewed or crushed.

Patients who have difficulty swallowing may be advised to dissolve the tablet in 100 ml of still water, stir until the tablet disintegrates, and then drink the suspension of microgranules immediately or within 30 minutes. Then fill the glass halfway with water, stir the remainder and drink. No other liquids should be used as they may damage the enteric coating. The microgranules should not be chewed or crushed.

For patients who have difficulty swallowing, the tablet can be administered via a nasogastric tube, after dissolving it in half a glass of still water. It is very important that the syringe and tube for this procedure are suitable.

Administration of the drug through a nasogastric tube:

Place the tablet in a suitable syringe and fill it with approximately 25 ml of water and 5 ml of air. Some tubes may require 50 ml of water to prevent the tablet from obstructing the tube. Shake the syringe for 2 minutes to disintegrate the tablet. Hold the syringe vertically, with the tip pointing upwards, and check the patency of the tip. Attach the syringe to the tube, holding it vertically. Shake the syringe and invert it with the tip pointing downwards. Quickly inject 5–10 ml of liquid. Invert the syringe after injection and shake again (the syringe should be held vertically to avoid clogging the tip). Invert the syringe again and inject another 5–10 ml of liquid into the tube. Repeat the procedure until the syringe is empty.
To flush out any remaining medication, fill the syringe with 25 ml of water and 5 ml of air, shake the syringe, invert it, and quickly inject the fluid. Some probes may require 50 ml of water.

Adults

Gastroesophageal reflux disease (GERD):

Treatment of erosive reflux esophagitis: 40 mg once daily for 4 weeks. An additional 4 weeks of therapy are recommended for patients in whom esophagitis has not been cured or its symptoms persist. Long-term treatment of patients with cured esophagitis to prevent relapse: 20 mg once daily. Symptomatic treatment of gastroesophageal reflux disease: 20 mg once daily in patients without esophagitis. If after 4 weeks of treatment, control of symptoms has not been achieved, the patient should undergo additional examination. After the disappearance of symptoms, the use of 20 mg once daily may be sufficient for their further control. For adults, an “as needed” regimen can be used: 20 mg once daily. For patients who have used NSAIDs and who are at risk of developing gastric or duodenal ulcers, further control of symptoms using the “as needed” regimen is not recommended.

In combination with antibacterial 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 Ezonexa® with 1 g amoxicillin and 500 mg clarithromycin 2 times a day for 7 days.

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

Treatment and prevention of ulcers caused by long-term use of NSAIDs: the recommended dose is 20 mg once a day, duration of treatment is 4–8 weeks; prevention of gastric and duodenal ulcers associated with NSAID treatment in patients at risk: the recommended dose is 20 mg once a day.

Long-term treatment after intravenous administration of the drug for the prevention of recurrent bleeding from peptic ulcers: 40 mg once a day for 4 weeks after intravenous administration of the drug for the prevention of recurrent bleeding from peptic ulcers.

Treatment of Zollinger-Ellison syndrome: 40 mg 2 times a day. The dosage should be selected individually, the duration of treatment is determined by clinical indications. According to the obtained clinical data, in most patients, control of the condition is achieved when taking doses of 80 and 160 mg of esomeprazole per day. If the dose exceeds 80 mg/day, it should be divided into two doses.

Patients of special groups

Patients with renal impairment

No dose adjustment is required for patients with renal impairment. Due to the lack of experience with Ezonexa® in patients with severe renal insufficiency, the drug should be administered with caution to such patients (see section "Pharmacological properties").

Liver dysfunction

No dose adjustment is required in patients with mild to moderate hepatic impairment. For patients with severe hepatic impairment, the maximum dose of Ezonexa® should not exceed 20 mg (see section 5.1).

Elderly patients

Dose adjustment is not required for elderly patients.

Pediatric population

Children under 12 years old

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 take 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. After symptoms have been controlled, further control can be achieved by using the drug at a dose of 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

The drug should not be used in children under 12 years of age, as there is no data on such use.

It is used in children over 12 years of age for the following indications:

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.

Overdose

Data on overdose are limited. Gastrointestinal symptoms and weakness have been described after taking 280 mg of esomeprazole. A single dose of 80 mg of esomeprazole is unlikely to cause serious adverse effects. No specific antidote is known.

Esomeprazole is highly bound to plasma proteins, so hemodialysis is ineffective. Treatment is symptomatic.

Adverse reactions

The reactions are listed according to their frequency of occurrence: very common (> 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); very rare (< 1/10,000); frequency unknown (cannot be estimated from the available data).

Blood and lymphatic system disorders

Rare: leukopenia, thrombocytopenia.

Very rare: agranulocytosis, pancytopenia.

On the part of the immune system

Rare: hypersensitivity reactions such as fever, angioedema and anaphylactic reaction/shock.

Metabolism and nutrition

Uncommon: peripheral oedema.

Rare: hyponatremia.

Frequency not known: hypomagnesemia (see section