Neksium of a granule

General characteristics. Structure:

One package contains:
active agent: esomeprazole magnesium trihydrate 11,1 mg equivalent to 10 mg of esomeprazole;
excipients: methacrylic acid and ethyl acrylate mg copolymer (1:1) 9,5, talc of 8,4 mg; sucrose, spherical granules (sugar, spherical granules) (the size 0,250 – 0,355 mm) 7,4 mg, a hypro rod of 32,2 mg, a gipromelloza of 1,7 mg, triethyl citrate of 0,95 mg, magnesium stearate of 0,65 mg, a glitserola mg monostearate 40-55 0,48, Polisorbat of 80 0,27 mg, Dextrosum of 2813 mg, кросповидон 75 mg, xanthane gum of 75 mg, citric acid of anhydrous 4,9 mg, dye iron oxide of yellow 1,8 mg.
Description
Pale yellow granules of various size (bulk – tonkoizmelchenny granules and larger – pellets). Brownish granules can meet.

Pharmacological properties:

Pharmacodynamics. Esomeprazole is S-isomer of an omeprazol and reduces secretion of hydrochloric acid in a stomach by specific inhibition of a proton pomp in covering cells
stomach. S-and R-isomers of an omeprazol have similar pharmakodinamichesky activity.
Action mechanism
Esomeprazole is the weak basis which passes into an active form in strongly acid medium of secretory tubules of covering cells of a mucous membrane of a stomach and inhibits a proton pomp – H+/K enzyme +-to ATFAZ, at the same time occurs inhibition of both basal, and stimulated secretion of hydrochloric acid.
Influence on secretion of acid in a stomach
Effect of esomeprazole develops within 1 hour after oral administration of 20 mg or 40 mg. At daily administration of drug within 5 days in a dose of 20 mg once a day average maximum concentration of hydrochloric acid after stimulation by Pentagastrinum decreases by 90% (at measurement of concentration of acid in 6-7 hours
after administration of drug for the 5th day of therapy). At patients with a gastroesophageal reflux disease is (GERB) and existence of clinical symptoms in 5 days of daily oral administration of esomeprazole in
to dose of 20 mg or 40 mg value intragastric рН higher than 4 was maintained within, on average, 13 and 17 hours from 24 hours. Against the background of reception of esomeprazole in a dose of 20 mg a day, value intragastric рН higher than 4 was maintained not less than 8, 12 and 16 hours at 76%, 54% and 24% of patients, respectively. For 40 mg of esomeprazole this ratio makes 97%, 92% and 56%, respectively.
Correlation between concentration of drug in plasma and inhibition of secretion of hydrochloric acid (for assessment of concentration used the AUC parameter (the area under a curve "concentration - time") is revealed.
The therapeutic effect reached as a result of inhibition of secretion of hydrochloric acid
At administration of drug of Neksium® in a dose of 40 mg healing the reflux esophagitis comes approximately at 78% of patients in 4 weeks of therapy and at 93% - in 8 weeks of therapy.
Treatment by the drug Neksium® in a dose of 20 mg 2 times a day in a combination with the corresponding antibiotics within one week leads to a successful eradikation of Helicobacter pylori approximately at 90% of patients.
Patients with an uncomplicated peptic ulcer after a week eradikatsionny course do not need the subsequent monotherapy by the drugs lowering secretion of glands of a stomach for healing of an ulcer and elimination of symptoms.
Efficiency of the drug Neksium® at the bleeding from a round ulcer confirmed with an endoscopic research was shown.
Use at GERB for children (at the age of 1-11 years)
The healing of an erosive esophagitis confirmed with data of an endoscopic research was observed at 93,3% of patients at the age of 1-11 years in 8 weeks of therapy by the drug Neksium®. Patients with body weight less than 20 kg accepted Neksium® 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 connected with inhibition of secretion of hydrochloric acid
During treatment by the drugs lowering secretion of glands of a stomach, concentration of gastrin in plasma increases as a result of decrease in secretion of hydrochloric acid. Owing to decrease in secretion of hydrochloric acid concentration of chromogranin A (CgA) increases. Increase in concentration of CgA can exert impact on results of inspections for detection of neuroendocrinal tumors. For prevention of this influence it is necessary to stop temporarily reception of esomeprazole in 5 days prior to carrying out a research of concentration of CgA.
At patients, the long time receiving esomeprazole, is noted increase in quantity of enterokhromaffinopodobny cells probably connected with increase in concentration of gastrin in plasma.
At the patients accepting the drugs lowering secretion of glands of a stomach during a long period formation of ferruterous cysts in a stomach is more often noted. These phenomena are caused by physiological changes in result of the expressed inhibition of secretion of hydrochloric acid. Cysts high-quality are also exposed to involution.
Use of the medicines suppressing secretion of hydrochloric acid in a stomach including, inhibitors of a proton pomp, is followed by increase in contents in a stomach of the microbic flora which normal is present at digestive tract. Use of inhibitors of a proton pomp can lead to insignificant increase in risk of infectious diseases of the digestive tract caused by Salmonella spp., Campylobacter spp. and probably Clostridium difficile at the hospitalized patients.
Нексиум® showed the best efficiency in comparison with ranitidine concerning healing of stomach ulcers at the patients receiving non-steroidal anti-inflammatory drugs (NPVP) including the selection inhibitors of cyclooxygenase-2 (TsOG-2).
Нексиум® showed high performance concerning prevention of stomach ulcers and a duodenum at the patients receiving NPVP (the age group is more senior than 60 years and/or with a round ulcer in the anamnesis), including the selection TsOG-2 inhibitors.

Pharmacokinetics. Absorption and distribution. Esomeprazole is unstable in acid medium therefore for oral administration use the tablets containing drug granules which cover is steady against action of a gastric juice. In the conditions of in vivo only an insignificant part of esomeprazole turns into R-isomer. Drug is quickly absorbed: the maximum concentration in plasma is reached in 1-2 hours after reception. Absolute bioavailability of esomeprazole after a single dose of a dose of 40 mg makes 64% and increases up to 89% against the background of daily reception once a day. For a dose of 20 mg of esomeprazole these indicators make 50% and 68%, respectively. Distribution volume at equilibrium concentration at healthy people makes about 0,22 l/kg of body weight. Esomeprazole contacts proteins of plasma for 97%.
Meal slows down and reduces absorption of esomeprazole in a stomach, however it has no significant effect on efficiency of inhibition of secretion of hydrochloric acid.
Metabolism and excretion. Esomeprazole is exposed to metabolism with participation of system of P450 cytochrome. The main part is metabolized with the participation of a specific polymorphic isoenzyme of CYP2C19, at the same time hydroxylated and desmetilirovanny metabolites of esomeprazole are formed. Metabolism of the rest is carried out by CYP3A4 isoenzyme; at the same time it is formed sulfoderivative esomeprazole, being the main metabolite defined in plasma.
The parameters specified below reflect, generally character of pharmacokinetics at patients with a superactivity of an isoenzyme of CYP2C19.
The general clearance makes about 17 l/h after a single dose of drug and 9 l/h – after multiple dose. The elimination half-life makes 1,3 hours at systematic reception once a day. The area under a curve "concentration time" (AUC) increases at repeated reception of esomeprazole. Dozozavisimy increase in AUC at repeated reception of esomeprazole has nonlinear character that is a consequence of decrease in metabolism at "the first passing" through a liver, and also decrease in system clearance probably of CYP2C19 isoenzyme caused by inhibition esomeprazole and/or to its sulfoderivatives. At daily reception once a day esomeprazole is completely removed from a blood plasma in a break between receptions and does not kumulirut.
The main metabolites of esomeprazole do not influence secretion of gastric acid. At oral administration to 80% of a dose it is removed in the form of metabolites with urine, other quantity is removed with excrements. In urine less than 1% of not changed esomeprazole are found.
Features of pharmacokinetics in some groups of patients. Approximately at 2,9±1,5% of the population activity of an isoenzyme of CYP2C19 is reduced. Such patients have an esomeprazole metabolism, is generally carried out as a result of action of CYP3A4. At systematic reception of 40 mg of esomeprazole once in days average AUC value for 100% exceeds value of this parameter at patients with a superactivity of an isoenzyme of CYP2C19. Average values of the maximum concentration in plasma at patients with reduced activity of an isoenzyme are increased approximately for 60%. The specified features do not influence a dose and a route of administration of esomeprazole.
At patients of advanced age (71-80 years) metabolism of esomeprazole does not undergo considerable changes.
After a single dose of 40 mg of esomeprazole average AUC value at women for 30% exceeds that at men. At daily administration of drug once a day distinctions in pharmacokinetics at men and women are not noted. The specified features do not influence a dose and a route of administration of esomeprazole.
At patients with a slight and moderate liver failure metabolism of esomeprazole can be broken. At patients with a heavy liver failure the speed of metabolism is reduced that leads to increase in AUC value for esomeprazole twice. For patients with a heavy liver failure it is not necessary to exceed the maximum daily dose - 20 mg. At reception once a day cumulation of esomeprazole and its main metabolites was not noted.
Studying of pharmacokinetics at patients with a renal failure was not carried out. As through kidneys removal not of the esomeprazole, but its metabolites is carried out, it is possible to believe that metabolism of esomeprazole at patients with a renal failure does not change.
Children at the age of 12-18 years after repeated reception have 20 mg and 40 mg of esomeprazole AUC value and time of achievement of the maximum concentration (tmax) in a blood plasma was similar to AUC and tmax values at adults.
At children at the age of 1-11 years after repeated reception of 10 mg of esomeprazole AUC value was similar to AUC value at teenagers and adults at reception of 20 mg of esomeprazole.
At children at the age of 1-11 years after repeated reception of 20 mg of esomeprazole AUC value was 6-11 times higher than AUC value at teenagers and adults at reception of 20 mg of esomeprazole.

Indications to use:

GERB:
- treatment erosive a reflux esophagitis - the prolonged supporting treatment after healing erosive a reflux - an esophagitis for prevention of a recurrence - a symptomatic treatment of GERB
Peptic ulcer of a stomach and duodenum
As a part of a combination therapy:
- treatment of an ulcer of the duodenum associated with Helicobacter pylori
- prevention of a recurrence of the round ulcer associated with Helicobacter pylori
Long kislotopodavlyayushchy therapy at the patients who had bleeding from a round ulcer (after intravenous use of the drugs lowering secretion of glands of a stomach for prevention of a recurrence).
Patients, it is long the accepting NPVP:
- healing of the stomach ulcer connected with reception of NPVP
- prevention of the stomach ulcer and a duodenum tied with reception of NPVP at the patients belonging to risk group
Zollingera-Ellison's syndrome or other states which are characterized by pathological hypersecretion of glands of a stomach, including, idiopathic hypersecretion.

Route of administration and doses:

Нексиум® in a dosage form of the pellets covered with a kishechnorastvorimy cover, and granules for preparation of suspension for intake it is intended, mainly, for patients of children's age and persons with swallowing difficulty.
Inside. For reception of 10 mg of the drug Neksium® it is necessary to pour out contents of one package in the glass containing 15 ml of water. For reception of 20 mg of the drug Neksium® it is necessary to pour out contents of 2 packages in the glass containing 30 ml of water. For reception of 40 mg of the drug Neksium® it is necessary to pour out contents of 4 packages in the glass containing 60 ml of water. Contents of a glass should be mixed and waited several minutes that suspension was formed. Suspension can be accepted inside at once or within 30 minutes after preparation, having once again mixed before the use. Then it is necessary to add to a glass 15 ml of water again, to stir the remains and to accept inside. It is not necessary to use sparkling water. Pellets and a granule cannot be chewed or split up.
Suspension can be entered via the nazogastralny probe. Instructions on preparation and administration of drug via the nazogastralny probe are provided in the section "Administration of Drug via the Nazogastralny Probe".
Children of 1-11 years with body weight ≥ 10 kg
GERB
Treatment erosive reflux esophagitis: for patients with body weight more than 10 kg, but less than 20 kg – on 10 mg once a day within 8 weeks. For patients with the body weight of 20 kg and more – on 10 mg or 20 mg once a day within 8 weeks.
Symptomatic treatment of GERB: on 10 mg once a day up to 8 weeks.
Use of esomeprazole in doses more than 1 mg/kg/days was not studied.
Adults and children since 12 years
GERB
Treatment erosive reflux esophagitis: on 40 mg once a day within 4 weeks.
The additional 4-week course of treatment in cases when after the first course healing of an esophagitis does not occur is recommended or symptoms remain. The prolonged supporting treatment after healing erosive a reflux esophagitis for prevention of a recurrence: on 20 mg once a day.
Symptomatic treatment of GERB: 20 mg once a day - to patients without esophagitis. If after 4 weeks of treatment symptoms do not disappear, it is necessary to conduct additional examination of the patient. After elimination of symptoms it is possible to switch over to the mode of administration of drug "if necessary", i.e. to accept Neksium® on 20 mg once a day when resuming symptoms. For the patients accepting NPVP and belonging to risk group of development of stomach ulcer or a duodenum treatment in the mode "in need of" is not recommended.
Adults
Peptic ulcer of a stomach and duodenum
As a part of a combination therapy for an eradikation with Helicobacter pylori:
· treatment of an ulcer of the duodenum associated with Helicobacter pylori: ÌѬ߿Ҽ® 20 mg, amoxicillin of 1 g and кларитромицин 500 mg. All drugs are accepted two times a day within 1 week.
· prevention of a recurrence of the round ulcers associated with Helicobacter pylori: ÌѬ߿Ҽ® 20 mg, amoxicillin of 1 g and кларитромицин 500 mg. All drugs are accepted two times a day within 1 week.
Long kislotopodavlyayushchy therapy at the patients who had bleeding from a round ulcer (after intravenous use of the drugs lowering secretion of glands of a stomach for prevention of a recurrence):
ÌѬ߿Ҽ® 40 mg of 1 times a day within 4 weeks after the end of intravenous therapy by the drugs lowering secretion of glands of a stomach.
Patients, it is long the accepting NPVP:
- healing of the stomach ulcer connected with reception of NPVP: ÌѬ߿Ҽ® 20 mg or 40 mg once a day. Duration of treatment makes 4-8 weeks.
- prevention of the stomach ulcer and a duodenum tied with reception of NPVP: ÌѬ߿Ҽ® 20 mg or 40 mg once a day.
The states connected with pathological hypersecretion of glands of a stomach, including, Zollingera-Ellison's syndrome and idiopathic hypersecretion: The recommended initial dose - Нексиум® 40 mg two times a day. Further the dose is selected individually, duration of treatment is defined by a clinical picture of a disease. There is an experience of use of drug in doses to 120 mg 2 times a day.
Children aged till 1 year or with body weight less than 10 kg: due to the lack of data on efficiency and safety it is not necessary to apply Neksium® at children aged till 1 year or with body weight less than 10 kg.
Renal failure: dose adjustment of drug is not required. However, experience of use of the drug Neksium® for patients with a heavy renal failure is limited; in this regard, at purpose of drug such patients should be careful (see the section "Pharmacokinetics").
Liver failure: at a slight and moderate liver failure dose adjustment of drug is not required. For patients with a heavy liver failure it is not necessary to exceed the maximum daily dose – 10 mg for patients at the age of 1-11 years and for patients 12 years are more senior than 20 mg.
Patients of advanced age: dose adjustment of drug is not required.
Administration of drug via the nazogastralny probe:
1. For introduction of 10 mg of the drug Neksium® to pour out contents of one package in the glass containing 15 ml of water.
2. For introduction of 20 mg of the drug Neksium® to pour out contents of 2 packages in the glass containing 30 ml of water.
3. For introduction of 40 mg of the drug Neksium® to pour out contents of 4 packages in the glass containing 60 ml of water.
4. Contents of a glass to mix and wait several minutes that suspension was formed.
5. To mix suspension once again and to gather it in the syringe.
6. To enter suspension at once or within 30 minutes after preparation.
7. To gain in the syringe 15 more 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) waters, to stir up the syringe and to enter the suspension remains into the nazogastralny probe.
Unused suspension should be destroyed.

Features of use:

In the presence of any alarming symptoms (for example, such as considerable spontaneous loss of body weight, repeated vomiting, a dysphagy, vomiting with impurity of blood or a melena), and also in the presence of stomach ulcer (or at suspicion of stomach ulcer) it is necessary to exclude existence of a malignant new growth as treatment by the drug Neksium® can lead to smoothing of symptomatology and delay diagnosis.
In rare instances at patients, a long time accepting омепразол, at a histologic research of bioptat of a mucous membrane of a body of a stomach atrophic gastritis came to light.
The patients accepting drug during the long period (especially over a year) have to be under regular observation of the doctor.
Long administration of drug is not shown to children and teenagers aged up to 12 years.
The patients accepting Neksium® "as necessary" have to be instructed about need to contact the doctor at change of character of symptoms. In view of fluctuations of concentration of esomeprazole in plasma at purpose of therapy "as necessary", it is necessary to consider interaction of drug with other medicines (see the section "Interaction with Other Medicines and Other Types of Medicinal Interaction"). At purpose of the drug Neksium® for an eradikation of Helicobacter pylori the possibility of medicinal interactions for all components of triple therapy has to be considered. Klaritromitsin is powerful inhibitor of an isoenzyme CYP3A4 therefore at purpose of eradikatsionny therapy to the patients receiving other drugs which are metabolized with participation of an isoenzyme of CYP3A4 (for example, a tsizaprida), it is necessary to consider possible contraindications and interactions of a klaritromitsin with these medicines. The drug Neksium® contain sucrose and a dextrose therefore they are contraindicated to patients with hereditary intolerance of fructose, glyukozo-galaktozny malabsorption or sakharazo-izomaltazny insufficiency.
INFLUENCE ON ABILITY TO DRIVE THE CAR AND OTHER MECHANISMS
Because during therapy dizziness, an illegibility of sight and drowsiness can be observed by the drug Neksium®, it is necessary to be careful at control of motor transport and other mechanisms.

Side effects:

The side effects which are not depending on the drug dosing mode, noted at drug Neksium® use are included below both during clinical trials, and at post-marketing studying.
Often
(> 1/100, <1/10)
Headache, abdominal pain, diarrhea, meteorism, nausea/vomiting, lock
Infrequently
(> 1/1000, <1/100)
Dermatitis, itch, rash, urticaria, drowsiness, sleeplessness, dizziness, paresthesias, dryness in a mouth, a sight illegibility, peripheral hypostases, increase in activity of "hepatic" enzymes
Seldom
(> 1/10000, <1/1000)
Hypersensitivity reactions (for example, fever, a Quincke's disease, anaphylactic reaction / an acute anaphylaxis), a bronchospasm, hepatitis (with jaundice or without), an arthralgia, a mialgiya, a leukopenia, thrombocytopenia, a depression, a hyponatremia, excitement, confusion, taste disturbance, stomatitis, digestive tract candidiasis, an alopecia, a photosensitization, an indisposition, perspiration
Very seldom
(<1/10000)
Agranulocytosis, pancytopenia, hallucinations, an agressive behavior, a liver failure, encephalopathy at patients with liver diseases, muscular weakness, intersticial nephrite, a gynecomastia, Stephens-Johnson's syndrome, a toxic epidermal necrolysis, a multiformny erythema, a hypomagnesiemia.

Interaction with other medicines:

Influence of esomeprazole on pharmacokinetics of other medicines. Decrease in acidity of a gastric juice against the background of treatment by esomeprazole can lead to change of absorption of drugs which absorption depends on acidity of the environment. As well as when using other drugs suppressing secretion of hydrochloric acid, or antiacid means, treatment by esomeprazole can lead to decrease in absorption of a ketokonazol or itrakonazol, and also to increase in absorption of digoxin. Joint reception of an omeprazol in a dose of 20 mg and digoxin increases once a day bioavailability of digoxin for 10% (bioavailability of digoxin increased at a size up to 30% at 20% of patients).
It was shown what омепразол interacts with some anti-retrovirus drugs. Mechanisms and clinical value of these interactions are not always known. Increase in value рН against the background of therapy omeprazoly can influence absorption of anti-retrovirus drugs. Interaction at the level of CYP2C19 isoenzyme is also possible. At joint purpose of an omeprazol and some anti-retrovirus drugs, such as атазанавир and нелфинавир, against the background of therapy omeprazoly, decrease in their concentration in serum is noted. Therefore their simultaneous use is not recommended. Joint purpose of an omeprazol (40 mg once a day) from atazanaviry 300 mg / to healthy volunteers led ritonaviry 100 mg to essential reduction of bioavailability of an atazanavir (the area under a curve "concentration – time", maximum (Cmax) and minimum (Cmin) of concentration decreased approximately by 75%). Increase in a dose of an atazanavir up to 400 mg did not compensate impact of an omeprazol on bioavailability of an atazanavir.
At co-administration of an omeprazol and sakvinavir increase in concentration of a sakvinavir in serum was noted, at appointment with some other anti-retrovirus drugs their concentration did not change. Considering similar pharmacokinetic and pharmakodinamichesky properties of an omeprazol and esomeprazole, combined use of esomeprazole with anti-retrovirus drugs, such as атазанавир and нелфинавир, it is not recommended.
Esomeprazole inhibits CYP2C19 - the main isoenzyme participating in his metabolism. Respectively, combined use of esomeprazole with other drugs in which metabolism CYP2C19 isoenzyme takes part such as diazepam, to tsitalopra, Imipraminum, кломипрамин, Phenytoinum, etc., can lead to increase in concentration of these drugs in plasma that, in turn, can demand a dose decline. It is especially important to remember this interaction at purpose of the drug Neksium® in the mode "as necessary". At joint reception of 30 mg of esomeprazole and diazepam which is CYP2C19 isoenzyme substrate, decrease in clearance of diazepam by 45% is noted.
Purpose of esomeprazole in a dose of 40 mg led to increase in residual concentration of Phenytoinum at patients with epilepsy for 13%. In this regard it is recommended to control concentration of Phenytoinum in plasma in an initiation of treatment esomeprazole and at its cancellation.
Purpose of an omeprazol in a dose of 40 mg led to increase in the area under a curve once a day "concentration – time" and Cmax of a vorikonazol (CYP2C19 isoenzyme substrate) for 15% and 41%, respectively.
Joint reception of warfarin from 40 mg of esomeprazole does not lead to change of time of coagulation at patients, is long accepting warfarin. However INR (the international normalized relation) at combined use of warfarin and esomeprazole was reported about several cases of clinically significant increase. It is recommended to control MNO at the beginning and upon termination of combined use of esomeprazole and warfarin or other derivatives of coumarin.
Esomeprazole, like an omeprazol, inhibits CYP2C19 isoenzyme. Joint reception of a tsilostazol and 40 mg of an omeprazol leads to increase in pharmacokinetic parameters of a tsilostazol at healthy volunteers: Cmax and AUC for 18% and 26%, respectively. Similar parameters of one of active metabolites of a tsilostazol increase by 29% and 69%, respectively.
Joint reception of a tsizaprid from 40 mg of esomeprazole leads to increase in values of pharmacokinetic parameters of a tsizaprid at healthy volunteers: AUC - for 32% and an elimination half-life for 31%, however the maximum concentration of a tsizaprid in plasma at the same time considerably does not change. Insignificant lengthening of an interval of QT which was observed at monotherapy tsizapridy at addition of the drug Neksium® did not increase (see the section "Special Instructions").
Нексиум® does not cause clinically significant changes of pharmacokinetics of amoxicillin and quinidine.
Researches on assessment of short-term combined use of esomeprazole and Naproxenum or rofekoksib did not reveal clinically significant pharmacokinetic interaction.
Influence of medicines on esomeprazole pharmacokinetics.
Isoenzymes of CYP2C19 and CYP3A4 take part in metabolism of esomeprazole. Combined use of esomeprazole with klaritromitsiny (500 mg 2 times a day) which inhibits CYP3A4 isoenzyme, leads to increase in AUC value of esomeprazole twice. Combined use of esomeprazole and the combined inhibitor of isoenzymes of CYP3A4 and CYP2C19, for example, of a vorikonazol, can lead to more than 2-fold increase in AUC value for esomeprazole. As a rule, in such cases esomeprazole dose adjustment is not required. Dose adjustment of esomeprazole can be required at patients with a heavy abnormal liver function and at its prolonged use. Long administration of drug is not shown to children and teenagers aged up to 12 years.
The medicines inducing isoenzymes of CYP2C19 and CYP3A4 such as, rifampicin and drugs of the St. John's Wort which is made a hole at combined use with esomeprazole can lead to decrease in concentration of esomeprazole in a blood plasma due to esomeprazole metabolism acceleration.

Contraindications:

Hypersensitivity to esomeprazole, the replaced benzimidazoles or other ingredients which are a part of drug.
Hereditary intolerance of fructose, glyukozo-galaktozny malabsorption or sakharazo-izomaltazny insufficiency.
The children's age till 1 year or body weight less than 10 kg (due to the lack of data on efficiency and safety of use of drug for this group of patients), children's age of 1-11 years (according to other indications, except treatment of an erosive esophagitis and a symptomatic treatment of GERB) and children's age is more senior than 12 years on others indications, except GERB.
Esomeprazole should not be accepted together with atazanaviry and nelfinaviry (see the section "Interaction with Other Medicines and Other Types of Medicinal Interaction").
With care – a heavy renal failure (experience of use is limited).
USE DURING PREGNANCY AND DURING BREASTFEEDING
There is no enough data on use of the drug Neksium® during pregnancy now. Results of epidemiological researches of the omeprazol representing racemic mix showed lack of fetotoksichesky action or disturbance of fetation.
At administration of esomeprazole the animal did not reveal any direct or indirect negative impact on development of an embryo or a fruit. Administration of racemic mix of drug also did not make any negative impact on animals during pregnancy, childbirth, and also during post-natal development.
It is necessary to appoint drug pregnant only in that case when the expected advantage for mother exceeds possible risk for a fruit.
It is not known whether esomeprazole with breast milk therefore it is not necessary to appoint Neksium® during feeding a breast is emitted.

Overdose:

Extremely exceptional cases of intentional overdose are currently described. Oral administration of esomeprazole in a dose of 280 mg was followed by the general weakness and symptoms from digestive tract. One-time reception of 80 mg of the drug Neksium® did not cause any negative effects. The antidote of esomeprazole is unknown. Esomeprazole well contacts proteins of plasma therefore dialysis is ineffective. At overdose it is necessary to carry out the symptomatic and general supporting treatment.

Storage conditions:

At a temperature not above 25 °C, in the places unavailable to children. Period of validity 3 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

The pellets covered with a kishechnorastvorimy cover and granules for preparation of suspension for intake, 10 mg.
On 3042,7 mg of the pellets covered with a kishechnorastvorimy cover and granules (10 mg of esomeprazole), in the laminated 3-layer package (polyethyleneterephthalate/aluminium/polyethylene of low density). On 28 packages in a cardboard pack of the instruction on a medical use.