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

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- isomer omeprazole have a 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 gastric mucosa and inhibits the proton pump - the enzyme H⁺/TO⁺- ATPase, with the inhibition of both basal and stimulated secretion of hydrochloric acid.

Effect on the secretion of hydrochloric acid in the stomach

After ingestion of esomeprazole in a dose of 20 mg or 40 mg for 5 days, patients with gastroesophageal reflux disease (GERD) with symptoms had a decrease in the secretion of hydrochloric acid in the stomach for most of the day. The effect was the same for intravenous administration and for oral administration.

The analysis of pharmacokinetic data revealed the relationship between the inhibition of hydrochloric acid secretion and esomeprazole plasma concentration after ingestion (the concentration parameter was used to estimate the concentration AUC - area under the curve "concentration - time").

Against the background of the intravenous administration of 80 mg of esomeprazole within 30 minutes followed by prolonged intravenous infusion esomeprazole dose of 8 mg / hr for 23.5 hours gastric pH value was above 4 for, on average, 21 hours and 6 above - for 11-13 hours.

Therapeutic effect, achieved by inhibiting the secretion of hydrochloric acid

Healing of reflux esophagitis in oral reception esomeprazole 40

mg occurs in approximately 78% of patients after 4 weeks of therapy and in 93% of patients after 8 weeks of therapy.

The efficacy of the Nexium® preparation for bleeding from peptic ulcers confirmed endoscopically is shown.

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 who took esomeprazole inside for a long period of time, there was an increase amount enterochromaffin cells that

probably, is associated with an increase in the concentration of gastrin in the plasma. Clinical significance of this phenomenon is not.

In patients taking orally for a long time, drugs that reduce the secretion of the glands of the stomach, the formation of glandular cysts in the stomach was more often noted. These phenomena are caused by physiological changes due to inhibition of hydrochloric acid secretion. 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.

Children aged less than 1 month and aged 1-11 months against oral esomeprazole 0.5 mg / kg and 1.0 mg / kg, respectively, there was a decrease in the average percentage of time with the intragastric pH value is less than 4. The safety profile of esomeprazole in children is similar to that of adults.

Pharmacokinetics:

Distribution

The apparent volume of distribution in the equilibrium state in healthy people is approximately 0.22 l / kg body weight. Esomeprazole binds to plasma proteins by 97%.

Metabolism and excretion Esomeprazole undergoes complete metabolism involving the cytochrome P450 system. The main part is metabolized with the participation of a specific polymorphic isoenzyme CYP2C19, thus formed hydroxylated and desmethylated metabolites of esomeprazole. The metabolism of the remainder is carried out by isoenzyme CYP3A4; In this case, the sulfo derivative of esomeprazole is the main metabolite, which is determined in plasma.

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

The total plasma clearance is approximately 17 l / h after a single administration of the drug and 9 l / h - with repeated administration. Half-life

is 1,3 hour with repeated administration of the drug once a day. Area under the curve "concentration - time" (AUC) increases with repeated administration. This increase is time- and dose-dependent, which is a consequence of a decrease in metabolism during the "first passage" through the liver, as well as a decrease in system clearance, probably due to the fact that esomeprazole and / or its sulfo derivative inhibits the isoenzyme CYP2C19.

With daily application once a day esomeprazole is completely eliminated from the plasma in the interval between administrations, there is no tendency to cumulate esomeprazole.

With repeated intravenous administration of esomeprazole in a dose 40 mg the mean maximum concentration in plasma is approximately 13,6 μmol / l. When administered in similar doses, the average plasma maximum concentration is 4,6 μmol / l.The total exposure is slightly reduced (approximately 30%) with intravenous administration of esomeprazole compared with oral administration.

When intravenously administered esomeprazole in doses 40 mg, 80 mg and 120 mg for 30 min, followed by intravenous administration in a dose 4 mg / h or 8 mg / hr for 23,5 h, a linear relationship was shown AUC of the administered dose.The main metabolites of esomeprazole do not affect the secretion of hydrochloric acid in the stomach. When administered orally, up to 80% of the dose of esomeprazole is excreted as metabolites by the kidneys, the other part by the intestine. In urine, less than 1% of unchanged esomeprazole is found.

Peculiarities of pharmacokinetics in some patient groups Approximately 2.9 ± 1.5% of the population has decreased isoenzyme activity CYP2C19. In such patients, the metabolism of esomeprazole is mainly carried out with the help of CYP3A4, and with the repeated ingestion of 40 mg of esomeprazole once a day, the average area under the concentration-time curve is 100% higher than 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%. Similar differences were found with intravenous administration of esomeprazole.The noted features do not affect the dose and way of using esomeprazole.

In elderly patients (71-80 years), the metabolism of esomeprazole does not change significantly.

In patients with mild and moderate impairment of liver function, esomeprazole metabolism may be impaired. Have patients with severe impairment of liver function, the metabolic rate is reduced, which leads to a doubling of the area under the concentration-time curve for esomeprazole. Trends in the cumulation of esomeprazole and its major metabolites with the introduction of the drug once a day is not noted. The study of pharmacokinetics in patients with reduced renal function was not performed. Since excretion of not esomeprazole itself, but its metabolites through the kidneys, it can be assumed that the metabolism of esomeprazole in patients with impaired renal function does not change.

Use in children

A study of the pharmacokinetics of esomeprazole in children aged 0 to 18 years was performed after a 3-minute intravenous injection once a day for 4 days. The maximum equilibrium concentration of the drug in the blood plasma (C_{ss, max}) was evaluated 5 minutes after dosing in children in all age groups, and in adult patients - 7 minutes after dosing 40 mg and at the end of the infusion of 20 mg dose.

The table presents the results of assessing the systemic exposure of esomeprazole in the form of geometric means (range).

Age	Dose	AUC,	C_{ss, max}
Group		μmol / l	μmol / l
0-1 months. *	0.5 mg / kg	7,5	3,7
	(n = 6)	(4,5-20,5)	(2,7-5,8)
1-11 months *	1.0 mg / kg	10,5	8,7

	(n = 6)	(4,5-22,2)	(4,5-14,0)
1-5 years	10 mg (n = 7)	7,9 (2,9-16,6)	9,4 (4,4-17,2)
6-11 years old	10 mg (n = 8)	6,9 (3,5-10,9)	5,6 (3,1-13,2)
	20 mg (n = 8) 20 mg (n = 6) **	14,4 (7,2-42,3) 10,1 (7,2-13,7)	8,8 (3,4-29,4) 8,1 (3,4 - 29,4)
12-17 years old	20 mg (n = 6)	8,1 (4,7-15,9)	7,1 (4,8-9,0)
	40 mg (n = 8)	17,6 (13,1-19,8)	10,5 (7,8-14,2)
Adults	20 mg (n = 22)	5,1 (1,5-11,8)	3,9 (1,5-6,7)
	40 mg (n = 41)	12,6 (4,8-21,7)	8,5 (5,4-17,9)
* The age group from 0 to 1 month included patients with adjusted age (the amount of fetal age and age after birth in full weeks) > 32 full weeks and <44 full weeks. The age group from 1 to 11 months included patients with adjusted age > 44 full weeks. ** Two patients were excluded - one due to reduced isoenzyme activity CYP2C19, the second - in connection with the concomitant use of the inhibitor of isoenzyme CYP3A4.
According to the constructed model C_{ss, max} after intravenous administration of esomeprazole in the form of a 10-minute, 20-minute and 30-minute infusion will decrease, on average, by 37% -49%, 54% -66% and 61% -72%, respectively, in all age groups and dosing groups in comparison with the value Css, mOh after a 3-minute injection.

Indications:

Adults

- as an alternative to oral therapy when it is impossible to conduct:

- with gastroesophageal reflux disease in patients with esophagitis and / or severe symptoms of reflux disease

- for the healing of peptic ulcers associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs)

- for the prevention of peptic ulcers associated with the intake of NSAIDs in patients at risk

- to prevent the recurrence of bleeding from the peptic ulcer after endoscopic hemostasis.

Children (aged 1 to 18 years)

- as an alternative to oral therapy when it is impossible to conduct:

with gastroesophageal reflux disease in patients with erosive reflux esophagitis and / or severe symptoms of reflux disease.

Contraindications:

Hypersensitivity to esomeprazole, substituted benzimidazoles or other ingredients of the drug.

Children under 1 year old and children under 18 years of age according to other indications, except gastroesophageal reflux disease. Esomeprazole should not be taken together with atazanavir and nelfinavir (see section "Interaction with other drugs and other interactions").

Carefully:

patients with severe renal disease insufficiency.

Pregnancy and lactation:

Currently, data on the use of esomeprazole during pregnancy are limited. In animal studies, no direct or indirect adverse effect of Nexium® on the development of an embryo or fetus has been identified. 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 during pregnancy should only be when the expected benefit to the mother exceeds the possible risk to the fetus.

There is no data on the use of the drug by women during lactation. It is not known whether esomeprazole with breast milk, so do not prescribe Nexium® during breastfeeding. If Nexium® is needed during lactation, the possibility of stopping breastfeeding should be considered.

Dosing and Administration:

Adults

As an alternative to oral therapy when it is not possible:

If oral therapy is not possible, patients may be recommended esomeprazole parenterally in a dose of 20-40 mg once a day.

- When gastroesophageal reflux disease in patients with esophagitis is recommended esomeprazole in a dose of 40 mg once a day. To treat the symptoms of GERD, Nexium® is used at a dose of 20 mg once a day.

- For the healing of peptic ulcers associated with the administration of NSAIDs in patients at risk, it is recommended that esomeprazole in a dose of 20 mg once a day.

For the prevention of peptic ulcers associated with the intake of NSAIDs, it is recommended that esomeprazole in a dose of 20 mg once a day.

As a rule, the period of treatment with the intravenous form is short, the patient should be transferred to oral intake as soon as possible.

To prevent the recurrence of bleeding from the peptic ulcer after endoscopic hemostasis:

After endoscopic hemostasis is recommended esomeprazole in a dose of 80 mg in the form of an intravenous infusion for 30 minutes followed by a prolonged intravenous infusion of esomeprazole at a dose of 8 mg / h for 3 days (72 hours). After the completion of parenteral therapy to suppress acid secretion, antisecretory therapy is recommended (for example, esomeprazole 40 mg once a day for 4 weeks).

Injection Dose 40 mg

A prepared solution of esomeprazole (5 ml, 8 mg / ml) is administered intravenously for at least 3 minutes.

A dose of 20 mg

Half of the prepared solution of esomeprazole (2.5 ml, 8 mg / ml) is administered intravenously for at least 3 minutes. Unused solution residues must be disposed of.

Infusion Dose 40 mg

The prepared esomeprazole solution is administered as an intravenous infusion for 10-30 minutes.

A dose of 20 mg

Half of the prepared solution of esomeprazole is administered as an intravenous infusion for 10-30 minutes. Unused solution residues must be disposed of.

A dose of 80 mg

The prepared esomeprazole solution is administered as an intravenous infusion for 30 minutes.

A dose of 8 mg / h

The prepared esomeprazole solution is administered as an extended intravenous infusion for 71.5 hours (8 mg / h). (The conditions and the shelf life of the prepared solution, see "Preparing the solution.")

Children (aged 1 to 18 years)

As an alternative to oral therapy when it is impossible to carry out. "

- with gastroesophageal reflux disease in patients with erosive reflux esophagitis and / or severe symptoms of reflux disease - esomeprazole parenterally once a day as part of a course of GERD therapy (recommendations for dosing are presented in the table).

As a rule, the period of treatment with intravenous form should be short, the patient should be transferred to oral intake as soon as possible.

Recommendations______ by______ dosing

esomeprazole for children

Age

Treatment of erosive reflux esophagitis

Symptomatic treatment of GERD

1-11 years old

Body weight less than 20 kg: 10 mg once a day Body weight 20 kg or more: 10 mg or 20 mg once a day

10 mg once a day

12-18

years

40 mg once a day

20 mg once a day

Injections A dose of 40 mg

A prepared solution of esomeprazole (5 ml, 8 mg / ml) is administered intravenously for at least 3 minutes.

A dose of 20 mg

Half of the prepared solution of esomeprazole (2.5 ml, 8 mg / ml) is administered intravenously for at least 3 minutes. Unused solution residues must be disposed of.

A dose of 10 mg

1.25 ml of the prepared solution of esomeprazole (8 mg / ml) is administered intravenously for at least 3 minutes.

Unused solution residues must be disposed of.

Infusion Dose 40 mg

The prepared esomeprazole solution is administered as an intravenous infusion for 10-30 minutes.

A dose of 20 mg

Half of the prepared solution of esomeprazole is administered as an intravenous infusion for 10-30 minutes. Unused solution residues must be disposed of.

A dose of 10 mg

A quarter of the prepared esomeprazole solution is administered as an intravenous infusion for 10-30 minutes. Unused solution residues must be disposed of.

The conditions and the shelf life of the prepared solution, see "Preparing the solution".

Impaired renal function

Correction of the dose of Nexium® in patients with impaired renal function is not required. Due to the limited experience of using Nexium® in patients with severe renal insufficiency, caution should be exercised in the treatment of such patients (see section "Pharmacokinetics").

Impaired liver function

GERD: correction of the dose of Nexium® in patients with mild and moderate liver dysfunction is not required. In patients with severe impairment of liver function, the maximum daily dose is 20 mg (see the section "Pharmacokinetics"),

Bleeding from the peptic ulcer: correction of the dose of Nexium® in patients with mild or moderate liver dysfunction is not required.In patients with severe impairment of liver function, the following mode of administration of Nexium® is recommended: 80 mg in the form of an intravenous infusion for 30 minutes followed by an extended intravenous infusion at a maximum dose of 4 mg / h for 71.5 hours (see "Pharmacokinetics" ).

Elderly patients

Correction of the dose of Nexium® in elderly patients is not required.

Preparation of the solution

The degradation of the prepared solution mainly depends on the pH value, and therefore only 0.9% sodium chloride solution for intravenous administration should be used to dissolve the drug.

The prepared solution should not be mixed or administered together with other drugs.

Before use, the solution should be assessed visually for no visible mechanical impurities and discoloration. Only a clear solution can be used. The prepared solution is recommended to enter immediately after preparation (from the microbiological point of view). The prepared solution should be used within 12 hours. Store at a temperature not exceeding 30 ° C.Unused residue should be disposed of in accordance with local regulations.

Injection 40 mg

Solution for injection (8 mg / ml) is prepared by adding 5 ml of 0.9% sodium chloride solution for intravenous injection into a bottle of 40 mg esomeprazole. The diluted esomeprazole solution is a clear liquid from colorless to pale yellow.

Infusion 40 mg

The infusion solution is prepared by dissolving the contents of one vial with 40 mg of esomeprazole in 100 ml of a 0.9% solution of sodium chloride for intravenous administration.

Infusion 80 mg

Infusion solution is prepared by dissolving the contents of two flasks with esomeprazole 40 mg in 100 ml of 0.9% sodium chloride solution for intravenous administration.

The diluted esomeprazole solution is a clear liquid from colorless to pale yellow.

Side effects:

Below are the side effects noted with intravenous and oral use of Nexium® during clinical trials and in the post-marketing study of Nexium® for oral administration.

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

Often: reactions at the injection site *

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.

Disorders of the psyche Infrequently: insomnia;

Rarely: depression, agitation,

confusion;

Rarely: hallucinations, aggressive behavior.

From the gastrointestinal tract Often: abdominal pain, constipation, diarrhea, flatulence, nausea / vomiting;

Infrequently: dry mouth;

Rarely: stomatitis, candidiasis of gastro-

intestinal tract;

Rarely: microscopic colitis

(confirmed histologically).

From the liver and bile excretory ways

Infrequently: increased activity

"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.

From 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 tract 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.

* Reactions at the site of administration of the drug were mainly observed in a clinical trial with a high dose of esomeprazole for 3 days (72 hours).In the pre-clinical study of esomeprazole, there was no irritant effect for intravenous administration, but a weak inflammatory response was observed with subcutaneous administration of the drug, depending on the concentration of esomeprazole.

Individual cases of irreversible visual impairment with intravenous administration of omeprazole to patients in critical condition have been reported, especially when high doses have been introduced, the cause-and-effect relationship with taking the drug has not been established.

Data on the safety of esomeprazole in children are consistent with the safety profile in adults.

Overdose:

At the moment, very rare cases of deliberate overdose are described. With oral administration of 280 mg of esomeprazole, weakness and symptoms from the gastrointestinal tract were described. Single intake of 80 mg esomeprazole by mouth and intravenous administration of 308 mg for 24 hours 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:

Studies on the study of interactions were conducted with the participation of only adult patients.

Effect of esomeprazole on the pharmacokinetics of other drugs Decrease in secretion of hydrochloric acid in the stomach during treatment with esomeprazole and decrease in absorption of ketoconazole, itraconazole and erlotinib, as well as increase in absorption of such drugs 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. Also

possible interaction at the level of

isoenzyme 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 use is not recommended.The combined use of omeprazole (40 mg once daily) with atazanavir 300 mg / ritonavir 100 mg by healthy volunteers resulted in a significant diminishing bioavailability of atazanavir (area under the concentration-time curve, 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. Joint use of esomeprazole with other drugs, in the metabolism of which takes part isoenzyme CYP2C19, such as diazepam, citalopram, imipramine, clomipramine, phenytoin , etc., can lead to an increase in the concentrations of these drugs in the plasma and require a dose reduction. When administered orally

joint intake of 30 mg of esomeprazole and diazepam by 45% reduces the clearance of diazepam, which is the substrate of the isoenzyme CYP2C19.

With the simultaneous administration of esomeprazole orally in a dose of 40 mg and phenytoin in patients with epilepsy, the residual concentration of phenytoin in plasma increased by 13%. In this regard, it is recommended to monitor the concentration 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 Stach voriconazole (substrate isoenzyme CYP2C19) by 15% and 41%, respectively. When using esomeprazole orally in a dose of 40 mg by patients receiving warfarin, the coagulation time remained within the allowed values. 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. In this regard, monitoring of INRs at the beginning and after the end of the joint application of these drugs is recommended.

Based on the results of the studies, the pharmacokinetic / pharmacodynamic interaction between clopidogrel (loading dose 300 mg and maintenance dose 75 mg / day) and

esomeprazole (40 mg / day inwards), which reduces the exposure of the active metabolite clopidogrel by an average of 40% and reduces 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 clopidogrel was used together with a fixed combination of 20 mg of esomeprazole and 81 mg of ASA, the exposure of the active metabolite of clopidogrel decreased by almost 40% compared to clopidogrel alone, with maximum inhibition levels

ADP-induced aggregation of platelets were the same, which is probably due to the simultaneous administration of ASA in a low dose.

The use of omeprazole at a dose of 40 mg once a day led to an increase in Stach and area under the concentration-time curve of cilostazol by 18% and 26%, respectively; for one of the active metabolites of cilostazol, the increase was 29% and 69%, respectively.

In healthy volunteers, the combined oral intake of esomeprazole 40 mg and cisapride 32% increased the area under the concentration-time curve (AUC) and increased the half-life by 31% (t¹/₂) for cisapride; the maximum concentrations of cisapride in plasma did not change significantly. Slight lengthening of the interval QT, which was observed with monotherapy with cisapride, did not increase with addition of esomeprazole (see section "Special instructions").

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

Some patients reported increased concentrations of methotrexate against a background of combined use with proton pump inhibitors. When prescribing high doses of methotrexate, consider temporary withdrawal of esomeprazole.

Shown, that esomeprazole does not cause clinically significant changes in the pharmacokinetics of amoxicillin and quinidine.

Studies on the study of the interaction of esomeprazole with other drugs when administered intravenously at high doses (80 mg followed by administration at a dose of 8 mg / h) were not carried out. Perhaps, with this dosing regime esomeprazole has a more pronounced effect on the pharmacokinetics of isoenzyme substrates CYP2C19. Therefore, patients should be under close medical supervision during intravenous administration of esomeprazole.

The effect of drugs on the pharmacokinetics of Nexium®

In the metabolism of esomeprazole, isozymes participate CYP2C19 and CYP3A4. Joint oral administration of esomeprazole and an isoenzyme inhibitor CYP3A4, clarithromycin (500 mg twice a day) leads to a twofold increase in the value AUC for esomeprazole.Joint use of esomeprazole and a combined inhibitor

isozymes CYP3A4 and CYP2C19, for example, voriconazole, can lead to more than a 2-fold increase in the value AUC for esomeprazole. how

Normally, in such cases, dosage adjustment 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. 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.

To dissolve the drug, only the drugs mentioned in the section "Preparation of the solution" should be used.

Special instructions:

In the presence of any anxiety symptoms (for example, such as significant spontaneous weight loss, recurrent vomiting, dysphagia, vomiting with blood or melena), and if there is a stomach ulcer (or suspected gastric ulcer), the presence of a malignant tumor should be excluded because 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.

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

Due to the fact that dizziness, blurred vision and drowsiness may occur during Nexium® treatment, care should be taken when driving vehicles and other mechanisms.

Form release / dosage:

Lyophilizate for the preparation of a solution for intravenous administration of 40 mg.

Packaging:

40 mg of esomeprazole in a 5 ml glass vial, sealed with a bromobutyl rubber stopper, wrapped in an aluminum crimp ring with a plastic lid.

10 bottles in a paper tripod with instructions for use in a cardboard box with the control of the first opening.

When packaged on Corden Pharma GmbH, Germany: 10 bottles in a paper tripod in a cardboard box with instructions for use.

Storage conditions:

Store in a dark place in the original packaging at a temperature of no higher than 30 ° C. Keep out of the reach of children.

A bottle without a cardboard bundle can be stored for no more than 24 hours under room lighting.

Shelf life:

2 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-000920

Date of registration:01.04.2011

The owner of the registration certificate:AstraZeneca ABAstraZeneca AB Sweden

Manufacturer: & nbsp

ASTRAZENECA, AB Sweden

CORDEN PHARMA, GmbH Germany

ORTAT, CJSC Russia

Representation: & nbspORTAT, CJSCORTAT, CJSC

Information update date: & nbsp07.05.2014

Illustrated instructions

Instructions

Nexium® (Nexium®)