Nexium - instructions for use, doses, side effects, contraindications

Excipients: methacrylic acid and ethyl acrylate copolymer (1: 1) 9.5 mg, talc 8.4 mg; sucrose, spherical granules (sugar, spherical granules) (size 0.250

- 0.355 mm) 7.4 mg, giprolose 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, citric acid anhydrous 4.9 mg, dye iron oxide yellow 1.8 mg.One package contains:

active substance: esomeprazole magnesium trihydrate 11.1 mg, equivalent to 10 mg esomeprazole;

Excipients: methacrylic acid and ethyl acrylate copolymer (1: 1) 9.5 mg, talc 8.4 mg; sucrose, spherical granules (sugar, spherical granules) (size 0.250

- 0.355 mm) 7.4 mg, giprolose 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, citric acid anhydrous 4.9 mg, dye iron oxide yellow 1.8 mg.

Description:Pale yellow granules of various sizes (bulk - fine granules and larger pellets). Brownish granules may occur.

Pharmacotherapeutic group:a means of reducing the secretion of the glands of the stomach - the proton pump inhibitor

ATX: & nbsp

A.02.B.C.05 Esomeprazole

Pharmacodynamics:

Esomeprazole is S-isomer omeprazole and reduces the secretion of hydrochloric acid in the stomach by specifically inhibiting the proton pump in parietal cells of the stomach. S- and R- isomers of omeprazole have similar pharmacodynamic activity. Mechanism of action

Esomeprazole is a weak base that transforms into an active form in a highly acidic secretory tubules of parietal cells of the mucosa casings of the stomach and inhibits the proton pump - enzyme H⁺/TO⁺- ATPase, thus inhibiting both basal and stimulated secretion of hydrochloric acid.

Effect on the secretion of hydrochloric acid in the stomach

The action of esomeprazole develops within 1 hour after oral administration of 20 mg or 40 mg. With daily intake of the drug 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 clinical symptoms after 5 days of daily oral esomeprazole at a dose of 20 mg or 40 mg, the intragastric pH above 4 was maintained for an average of 13 and 17 hours out of 24 hours. Against the background of taking esomeprazole at a dose of 20 mg per day, the intragastric pH above 4 was maintained for at least 8, 12 and 16 hours in 76%, 54% and 24% of patients, respectively.For 40 mg of esomeprazole, this ratio is 97%, 92% and 56%, respectively.

A correlation was found between plasma concentration in the plasma and inhibition of hydrochloric acid secretion (the concentration AUC (area under the curve "concentration - time")).

The therapeutic effect achieved in

as a result of inhibiting the secretion of hydrochloric acid

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

Treatment with Nexium® at a dose of 20 mg twice a day in combination with appropriate antibiotics for one week results in successful eradication Helicobacter pylori in about 90% of patients. Patients with uncomplicated peptic ulcer after a weekly eradication course do not need subsequent monotherapy with drugs that reduce the secretion of the glands of the stomach, to heal ulcers and eliminate symptoms.

The efficacy of the Nexium® preparation for bleeding from peptic ulcers confirmed by endoscopic examination was demonstrated. The use of GERD in children (aged 1-11 years)

Healing of erosive esophagitis, confirmed by endoscopic data, was observed in 93.3% of patients aged 1-11 years after 8 weeks of treatment with Nexium®. Patients weighing less than 20 kg took Nexium in a daily dose of 5 mg or 10 mg, and patients with body weight

more than 20 kg - in a daily dose of 10 mg or 20 mg.

Other effects associated with inhibition of hydrochloric acid secretion During treatment with drugs that reduce the secretion of the gland of the stomach, the concentration of gastrin in the plasma increases as a result of a decrease in the secretion of hydrochloric acid. Due to a decrease in the secretion of hydrochloric acid, the concentration of chromogranin A (CgA). Increase in concentration CgA can influence the results of examinations for the detection of neuroendocrine tumors. To prevent this effect, therapy with proton pump inhibitors should be stopped 5 to 14 days before the study concentration CgA. If during this time the concentration CgA did not return to the normal value, the study should be repeated.

In children and adult patients, long time received esomeprazole, there is an increase in the number of enterochromaffin-like cells, probably associated with an increase in the concentration of gastrin in the plasma.Clinical significance of this phenomenon is not.

In patients taking drugs that reduce the secretion of the glands of the stomach, for a long period of time, the formation of glandular

cysts in the stomach. These phenomena are caused by physiological changes as a result of pronounced inhibition of the secretion of hydrochloric acid. Cysts are benign and undergo reverse development.

The use of drugs suppressing the secretion of hydrochloric acid in the stomach, including proton pump inhibitors, is accompanied by an increase in stomach content in the microbial flora normally present in the gastrointestinal tract. The use of proton pump inhibitors can lead to a slight increase in the risk of infectious diseases of the gastrointestinal tract caused by Salmonella spp., Campylobacter spp. and, in hospitalized patients, Clostridium difficile.

Nexium® showed better efficacy compared to ranitidine for healing gastric ulcers in patients receiving non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2).

Nexium® has been shown to be highly effective in preventing gastric and duodenal ulcers in patients receiving NSAIDs (age group over 60 and / or peptic ulcer in the anamnesis), including selective inhibitors of COX-2.

Pharmacokinetics:

Absorption and distribution. Esomeprazole is unstable in an acidic environment, so for oral use, pellets are coated with an enteric coating. In conditions in vivo Only a small fraction of esomeprazole is converted into Risomer. The drug is quickly absorbed: the maximum concentration in the plasma is achieved 1-2 hours after ingestion. Absolute bioavailability of esomeprazole after a single dose of 40 mg is 64% and increases to 89% on the background of daily administration once a day. For a dose of 20 mg of esomeprazole, these values are 50% and 68%, respectively. The volume of distribution at equilibrium concentration in healthy people is approximately 0.22 l / kg body weight. Esomeprazole binds to plasma proteins by 97%.

Eating slows and reduces absorption of esomeprazole in the stomach, but this does not have a significant effect on the inhibition of hydrochloric acid secretion.

Metabolism and excretion. Esomeprazole undergoes a metabolism involving the cytochrome P450 system. The main part is metabolized with the participation of a specific polymorphic isoenzyme CYP2C19, at the same time hydroxylated and

desmethylated metabolites of esomeprazole. The metabolism of the remainder is carried out by isoenzyme CYP3A4; This produces a sulfo derivative of esomeprazole, which is the main metabolite, determined in plasma.

The parameters given below mainly reflect the nature of pharmacokinetics in patients with increased isoenzyme activity CYP2C19.

The total clearance is approximately 17 l / h after a single dose and 9 l / h - after repeated administration. The half-life is 1.3 hours with a systematic admission once a day. Area under the curve "concentration - time" (AUC) increases with repeated use of esomeprazole. Dose-dependent increase AUC with repeated administration of esomeprazole is non-linear, which is a consequence of a decrease in metabolism during the "first passage" through the liver, as well as a decrease in systemic clearance, probably caused by inhibition of the isoenzyme CYP2C19 esomeprazole and / or its sulfo derivative.With daily intake once a day esomeprazole completely removed from the blood plasma during a break between doses and does not cumulate.

The main metabolites of esomeprazole do not affect the secretion of gastric acid.

When administered orally, up to 80% of the dose is excreted in the form of metabolites with urine, the rest is excreted with feces. In urine, less than 1% of unchanged esomeprazole is found. Peculiarities of pharmacokinetics in some groups of patients. Approximately 2.9 ± 1.5% of the population has decreased isoenzyme activity CYP2C19. In such patients, the metabolism of esomeprazole is mainly due to the action of CYP3A4. With the systematic administration of 40 mg of esomeprazole, once a day, the mean AUC 100% higher than this parameter in patients with increased isoenzyme activity CYP2C19. The mean values of maximum plasma concentrations in patients with reduced isoenzyme activity were increased by approximately 60%. These features do not affect the dose and method of use of esomeprazole.

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

After a single dose of 40 mg esomeprazole, the mean AUC in women it is 30% higher than that of men. With daily intake of the drug once a day, there are no differences in pharmacokinetics in men and women. These features do not affect the dose and method of administration

esomeprazole.

In patients with mild and moderate hepatic insufficiency, the metabolism of esomeprazole may be impaired. In patients with severe hepatic insufficiency, the metabolic rate is reduced, which leads to an increase in the value AUC for esomeprazole 2 times. For patients with severe hepatic insufficiency do not exceed the maximum daily dose - 20 mg. When taking once a day, no cumulation of esomeprazole and its main metabolites was observed.

The study of pharmacokinetics in patients with renal insufficiency was not carried out. Because the kidneys exclude not the most esomeprazole, but its metabolites, it can be assumed that the metabolism of esomeprazole in patients with renal insufficiency does not change.

In children aged 12-18 years after repeated administration of 20 mg and 40 mg of esomeprazole, the value AUC and time to reach the maximum concentration (TCmah) in blood plasma was similar to the values AUC and TSmah in adults.

In children aged 1-11 years after repeated administration of 10 mg esomeprazole value AUC was similar to the meaning AUC in adolescents and adults with admission of 20 mg of esomeprazole.

In children aged 1-11 years after repeated admission of 20 mg esomeprazole value AUC was 6-11 times higher than the value AUC in adolescents and adults with admission of 20 mg of esomeprazole.

Indications:

GERD:

- treatment of erosive reflux esophagitis

- prolonged maintenance treatment after healing of erosive reflux esophagitis to prevent recurrence

- symptomatic treatment of GERD

Stomach ulcer and duodenal ulcer As part of combination therapy:

treatment of duodenal ulcers associated with Helicobacter pylori

- prevention of recurrences of peptic ulcers associated with Helicobacter pylori Long-term acid-suppressing therapy in patients who underwent bleeding from a peptic ulcer (after intravenous administration of drugs that reduce the secretion of the glands of the stomach, for the prevention of recurrence).

Patients taking long-term NSAIDs:

- healing of gastric ulcer associated with the intake of NSAIDs

-prophylaxis of gastric ulcer and duodenal ulcer associated with the intake of NSAIDs in patients at risk

Zollinger-Ellison syndrome or other conditions characterized by pathological hypersecretion of the glands of the stomach, including idiopathic hypersecretion.

Contraindications:

Hypersensitivity to esomeprazole, substituted benzimidazoles or other ingredients that make up the drug.

Hereditary intolerance to fructose, glucose-galactose malabsorption or sugar-isomaltase deficiency.

Children under 1 year of age or body weight less than 10 kg (due to lack of data on the effectiveness and safety of the drug in this group of patients), children 1-11 years of age (for other indications, except for the treatment of erosive esophagitis and symptomatic treatment of GERD) and Children's age is older than 12 years according to other indications, except for GERD.

Esomeprazole should not be taken together with atazanavir and nelfinavir (see section "Interaction with other drugs and other types of drug interactions").

Carefully:

- severe renal insufficiency (experience of use is limited).

Pregnancy and lactation:

At present, there is insufficient data on the use of Nexium® during pregnancy. The results of epidemiological studies of omeprazole, which is a racemic mixture, showed no fetotoxic effect or impaired fetal development.

With the introduction of esomeprazole, no direct or indirect adverse effects on the development of the embryo or fetus have been identified in animals. The introduction of the racemic mixture of the preparation also did not have any negative effect on animals during pregnancy, childbirth, and also during postnatal development. Prescribe the drug to pregnant women only if the expected benefit to the mother exceeds the possible risk to the fetus.

It is not known whether esomeprazole with breast milk, so do not prescribe Nexium® while breastfeeding.

Dosing and Administration:

Nexium® in the dosage form of pellets coated with an enteric coating and granules for the preparation of a suspension for ingestion is intended primarily for patients of childhood and those with difficulty swallowing.

Inside. To receive 10 mg of Nexium®, pour the contents of one packet into a beaker containing 15 ml of water. To receive 20 mg of Nexium ®, pour the contents of 2 packets into a glass containing 30 ml of water. To receive 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 mixed and wait a few minutes to form a suspension. The suspension can be taken orally within 30 minutes after preparation, once again mixed before use. Then again add 15 ml of water to the beaker, stir the leftovers and take them inside. Do not use carbonated water. Pellets and granules can not be chewed or crushed. The suspension can be administered via a nasogastric tube. Instructions for preparation and administration of the drug through the nasogastric tube are given in the section "Administration of the drug through the nasogastric tube".

Children 1-11 years old with a body weight> 10 kg GERD

Treatment of erosive reflux esophagitis: for patients with a body weight of more than 10 kg, but less than 20 kg - 10 mg once a day for 8 weeks. For patients with body weight

20 kg and more - 10 mg or 20 mg once a day for 8 weeks.

Symptomatic treatment GERD: 10 mg once a day to 8 weeks.

The use of esomeprazole in doses greater than 1 mg / kg / day has not been studied.

Adults and children from the age of 12 GERD

Treatment of erosive reflux esophagitis: 40 mg once a day for 4 weeks. It is recommended to have an additional 4-week course of treatment in cases when after the first course of healing the esophagitis does not come or the symptoms remain.

Long-term maintenance treatment after healing of erosive reflux esophagitis to prevent relapse: 20 mg once daily.

Symptomatic treatment of GERD: 20 mg once a day - for patients without esophagitis. If after 4 weeks of treatment the symptoms do not disappear, an additional examination of the patient should be carried out. After eliminating the symptoms, you can go to the drug intake mode "if necessary", i.e. take Nexium® 20 mg once a day with the resumption of symptoms. For patients taking NSAIDs and belonging to the group

risk of developing a stomach or duodenal ulcer, treatment is not recommended in the "if necessary" regime.

Adults

Stomach ulcer and duodenal ulcer As part of a 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 medications are taken twice a day for 1 week.

- prevention of recurrences of peptic ulcers associated with Helicobacter pylori:

Nexium® 20 mg, amoxicillin 1 g and clarithromycin 500 mg. All medications are taken twice a day for 1 week.

Long-term acid-suppressing therapy in patients who underwent bleeding from a peptic ulcer (after intravenous use of drugs that reduce the secretion of the glands of the stomach, to prevent relapse)

Nexium® 40 mg once a day for 4 weeks after the end of intravenous therapy with drugs that reduce the secretion of the glands of the stomach.

Patients taking long-term NSAIDs:

- healing of gastric ulcer associated with the intake of NSAIDs: Nexium® 20 mg or 40 mg once daily. The duration of treatment is 4-8 weeks.

- prevention of gastric ulcer and duodenal ulcer associated with the administration of NSAIDs: Nexium® 20 mg or 40 mg once daily.

Conditions associated with pathological hypersecretion of the gland of the stomach, including Zollinger-Ellison syndrome and idiopathic hypersecretion: The recommended initial 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 an experience of using the drug in doses up to 120 mg twice a day.

Children under the age of 1 year or with a body weight of less than 10 kg: due to lack of data on efficacy and safety, do not use Nexium ® in children under 1 year old or with a body weight of less than 10 kg.

Renal failure: dose adjustment is not required. However, experience with Nexium® in patients with severe renal insufficiency is limited; Therefore, when prescribing the drug, such patients should be careful (see section "Pharmacokinetics").

Hepatic failure: with mild and moderate hepatic insufficiency, dose adjustment is not required. For patients with severe hepatic insufficiency do not exceed the maximum daily dose - 10 mg for patients aged 1-11 years and 20 mg for patients over 12 years.

Elderly patients: dosage adjustment is not required.

Administration of the drug through the nasogastric tube:

1. To administer 10 mg of Nexium®, pour the contents of one packet into a beaker containing 15 ml of water.

1. To administer 20 mg of Nexium®, pour the contents of 2 packets into a glass,

containing 30 ml of water.

2. To administer 40 mg of Nexium®, pour the contents of 4 packets into a glass,

containing 60 ml of water.

3. Stir the contents of the beaker and wait for a few minutes to form a suspension.

4. Stir the suspension again and draw it into the syringe.

5. The suspension should be administered immediately or within 30 minutes after preparation.

6. Inject 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 suspension residues into the nasogastric tube.

Unused suspension should be disposed of.

Side effects:

The following side effects are independent of the dosing regimen of the drug, noted with the use of the drug Nexium®, both during clinical trials and in post-marketing studies.

The frequency of side effects is given in the form of the following gradation: very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000).

From the skin and subcutaneous tissues

Infrequently: dermatitis, itching, rashes, hives; Rarely: alopecia, photosensitivity; Rarely: multiform erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis.

From the musculoskeletal and connective tissue

Rarely: arthralgia, myalgia;

Rarely: muscle weakness.

From the nervous system Often: headache;

Infrequently: dizziness, paresthesia, drowsiness;

Rarely: a taste disorder."hepatic" enzymes;

Rarely: hepatitis (with jaundice or without);

Rarely: hepatic insufficiency, encephalopathy in patients with liver disease.

From the genitals and dairy glands

Rarely: gynecomastia.

From the side of blood and lymphatic systems

Rarely: leukopenia, thrombocytopenia;

Rarely: agranulocytosis, pancytopenia.

Co side of the immune system

Rarely: hypersensitivity reactions (eg, fever, angioedema, anaphylactic reaction / anaphylactic shock).

On the part of the respiratory system, organs of the chest and mediastinum

Rarely: bronchospasm.

From the side of the kidneys and urinary tracts Very rarely: interstitial nephritis.

From the side of the organ of vision Rarely: blurred vision.

From the side of metabolism and nutrition

Infrequently: peripheral edema;

Rarely: hyponatremia;

Rarely: hypomagnesemia; hypocalcemia due to severe hypomagnesemia, hypokalemia due to hypomagnesemia.

General disorders

Rarely: malaise, sweating.

Overdose:

At the moment, very rare cases of deliberate overdose are described. Oral administration of esomeprazole at a dose of 280 mg was accompanied by general weakness and symptoms from the gastrointestinal tract. One-time administration of 80 mg of the drug Nexium® did not cause any negative consequences. The antidote of esomeprazole is unknown. Esomeprazole binds well to plasma proteins, so dialysis is ineffective. In case of an overdose, it is necessary to carry out symptomatic and general supportive treatment.

Interaction:The effect of esomeprazole on the pharmacokinetics of other drugs. Decrease in secretion of hydrochloric acid in the stomach against the background of treatment with esomeprazole and other inhibitors of the proton pump

can lead to a decrease or increase in the absorption of drugs, the absorption of which depends on the acidity of the medium. Like other drugs that reduce the acidity of gastric juice, treatment with esomeprazole may lead to a decrease in absorption of ketoconazole, itraconazole and erlotinib, as well as increased absorption of drugs such as digoxin. Joint reception of omeprazole at a dose of 20 mg once a day and digoxin increases the bioavailability of digoxin by 10% (bioavailability of digoxin was increased by up to 30% in 20% of patients).

It was shown that omeprazole interacts with some antiretroviral drugs. The mechanisms and the clinical significance of these interactions are not always known. An increase in pH on the background of omeprazole therapy may affect the absorption of antiretroviral drugs. It is also possible to interact at the isoenzyme level CYP2C19. When combined use of omeprazole and some antiretroviral drugs, such as atazanavir and nelfinavir, against the background of therapy with omeprazole, there is a decrease in their concentration in the serum. Therefore, their simultaneous application is not recommended. The combined use of omeprazole (40 mg once daily) with atazanavir 300 mg / ritonavir 100 mg

healthy volunteers led to a significant decrease in the bioavailability of atazanavir (area under the curve "concentration - time", the maximum (Cmah) and minimal (Cmin) concentrations decreased by approximately 75%). An increase in the dose of atazanavir to 400 mg did not compensate for the effects 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, while with use with some other antiretroviral drugs their concentration did not change. Given the similar pharmacokinetic and pharmacodynamic properties of omeprazole and esomeprazole, the combined use of esomeprazole with antiretroviral drugs, such as atazanavir and nelfinavir, Not recommended.

Esomeprazole inhibits CYP2C19 - the main isoenzyme involved in its metabolism. Accordingly, the joint use of esomeprazole with other drugs in the metabolism of which isoenzyme participates CYP2C19, such as diazepam, citalopram, imipramine, clomipramine, phenytoin , etc., can lead to an increase in the concentrations of these drugs in the plasma, which, in turn, may require a dose reduction. About this interaction

it is especially important to remember when using Nexium® in the "as needed" mode. When co-administered 30 mg of esomeprazole and diazepam, which is a substrate of the isoenzyme CYP2C19, there is a decrease in clearance of diazepam by 45%.

The use of esomeprazole at a dose of 40 mg resulted in an increase in the residual concentration of phenytoin in patients with epilepsy by 13%. In this regard, it is recommended to monitor the concentrations of phenytoin in the plasma at the beginning of treatment with esomeprazole and when it is withdrawn. The use of omeprazole at a dose of 40 mg once a day led to an increase in the area under the concentration-time curve and Cmah voriconazole (substrate isoenzyme CYP2C19) by 15% and 41%, respectively.

The simultaneous administration of warfarin with 40 mg of esomeprazole does not lead to a change in coagulation time in patients taking long-term warfarin. However, several cases of a clinically significant increase in INR (an 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 after the end of the joint use of esomeprazole and warfarin or other coumarin derivatives.

Based on the results of the studies,

pharmacokinetic / pharmacodynamic interaction between clopidogrel (loading dose 300 mg and maintenance dose 75 mg / day) and esomeprazole (40 mg / day inwards), which leads to a decrease in the exposure of the activemetabolite of clopidogrel by an average of 40% and a decrease in the maximum inhibition of ADP-induced platelet aggregation by an average of 14%.

The clinical significance of this interaction is not clear. In a prospective study in patients receiving placebo or omeprazole in a dose of 20 mg / day. concurrent with clopidogrel and acetylsalicylic acid (ACA) therapy, and in the analysis of clinical outcomes of large-scale randomized trials, there was no evidence of an increased risk of cardiovascular complications in the combined use of clopidogrel and proton pump inhibitors, including esomeprazole. The results of a number of observational studies are contradictory and do not give an unambiguous answer about the presence or absence of an increased risk of thromboembolic cardiovascular complications against the combined use of clopidogrel and proton pump inhibitors.

When using clopidogrel together with a fixed combination of 20 mg esomeprazole and 81 mg ASA exposure

of the active metabolite of clopidogrel decreased by almost 40% compared to clopidogrel alone, with the maximum levels of inhibition of ADP-induced platelet aggregation being the same, which is probably due to the simultaneous administration of ASA at a low dose.

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

Joint use of cisapride with 40 mg of esomeprazole leads to an increase in the pharmacokinetic parameters of cisapride in healthy volunteers: AUC - 32% and half-life at 31%, but the maximum concentration of cisapride in the plasma does not change significantly. Slight lengthening of the interval QT, which was observed with monotherapy with cisapride, did not increase with the addition of the Nexium® preparation (see section "Special instructions").

With the simultaneous use of esomeprazole and tacrolimus, an increase in tacrolimus concentration in

blood serum.

Some patients reported increased concentrations of methotrexate against a background of 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 the short-term joint use of esomeprazole and naproxen or rofecoxib have not revealed a clinically significant pharmacokinetic interaction. Effect of drugs on the pharmacokinetics of esomeprazole.

In the metabolism of esomeprazole, isozymes participate CYP2C19 and CYP3A4. Joint use of esomeprazole with clarithromycin (500 mg 2 times a day), which inhibits the isoenzyme CYP3A4, leads to an increase in the value AUC esomeprazole 2 times. Joint use of esomeprazole and a combined inhibitor of isoenzymes CYP3A4 and CYP2C19, for example, voriconazole, can lead to more than 2-fold increase in the value AUC for esomeprazole. As a rule, in such cases, dosage correction of esomeprazole is not required. Correction of the dose of esomeprazole may be required in patients with severe impairment of liver function and with prolonged use. Long-term use of the drug is not indicated for children and adolescents under the age of 12 years. Medicines that induce isoenzymes CYP2C19 and CYP3A4, such as, rifampicin and preparations of St. John's wort penetrated, when combined with esomeprazole may lead to a decrease in the concentration of esomeprazole in the blood plasma by accelerating the metabolism of esomeprazole.

Special instructions:

In the presence of any anxiety symptoms (for example, such as significant spontaneous weight loss, repeated vomiting, dysphagia, vomiting with a trace of blood or melena), and if there is a stomach ulcer (or suspected gastric ulcer), the presence of a malignant tumor treatment with Nexium® can lead to a smoothing of the symptoms and delay the diagnosis.

In rare cases, patients who have been taking long-term omeprazole, histological examination of biopsy specimens of the mucous membrane of the body of the stomach revealed atrophic gastritis.

Patients taking the drug for a long period (especially

more than a year), should be under regular supervision of the doctor. Long-term use of the drug is not indicated for children and adolescents under the age of 12 years. Patients taking Nexium® "as needed" should be instructed to contact their physician if the symptoms change.Taking into account the fluctuations in the plasma esomeprazole concentration when administering therapy "as necessary", the interaction of the drug with other drugs should be taken into account (see the section "Interaction with other drugs and other types of drug interactions"). When prescribing Nexium® for eradication Helicobacter pylori the possibility of drug interactions for all components of triple therapy should be taken into account. Clarithromycin is a potent inhibitor of isoenzyme CYP3A4, therefore, in the appointment of eradication therapy to patients receiving other drugs metabolized with the participation of isoenzyme CYP3A4 (for example, cisapride), it is necessary to take into account possible contraindications and interactions of clarithromycin with these drugs.

The drug Nexium® contains sucrose and dextrose, therefore it is contraindicated

patients with hereditary intolerance to fructose, glucose galactose malabsorption or sugar-isomaltase deficiency.

Pharmacokinetic / pharmacodynamic interaction between clopidogrel (loading dose 300 mg and maintenance dose 75 mg / day) and esomeprazole (40 mg / day.inwardly), which leads to lower exposure to the active metabolite of clopidogrel on average 40% reduction in maximal inhibition of ADP-induced platelet aggregation in average 14%. Therefore, to avoid the simultaneous application of esomeprazole and clopidogrel (see. The section "interaction with other drugs and other types of drug interactions"). Separate observational studies indicate that proton pump inhibitor therapy may slightly increase the risk of osteoporosis-related fractures, but other similar studies have not shown an increased risk.

In a randomized, double-blind, controlled clinical studies of omeprazole and esomeprazole, including two open-label studies long-term treatment (over 12 years), no connection fracture was confirmed in the background

osteoporosis with the use of proton pump inhibitors.

Although the causal relationship between the use of omeprazole / esomeprazole with fractures against osteoporosis is not established, patients with a risk of developing osteoporosis or fractures against it should be under appropriate clinical supervision.

Effect on the ability to drive transp.cf. and fur:

Due to the fact that during the treatment with Nexium®, dizziness, blurred vision and drowsiness may occur, caution should be exercised when management of vehicles and other mechanisms.

Form release / dosage:

Pellets, coated with enteric coating, and granules for the preparation of a suspension for oral administration, 10 mg.

Packaging:

By 3042.7 mg of enteric coated pellets and granules (10 mg esomeprazole), in a laminated 3-layer package

(polyethylene terephthalate / aluminum / low density polyethylene). For 28 packages in a cardboard box with instructions for medical use.

Storage conditions:

At temperatures not higher than 25 ° C, in places inaccessible to children.

Shelf life:

3 of the year. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001170

Date of registration:11.11.2011

Date of cancellation:2016-11-11

The owner of the registration certificate:AstraZeneca ABAstraZeneca AB Sweden

Manufacturer: & nbsp

ASTRAZENECA, AB Sweden

Representation: & nbspAstraZeneca Pharmaceuticals Ltd.AstraZeneca Pharmaceuticals Ltd.

Information update date: & nbsp24.10.2013

Illustrated instructions

Instructions

Nexium® (Nexium®)