Structure

Active ingredient: esomeprazole;

1 capsule kishechnorastvorimy contains 40 mg of esomeprazole (in the form of dihydrate magnesium esomeprazole);

Excipients: sugar spherical (contains sucrose), povidone, sodium lauryl sulfate, opadray II white 85F28751, magnesium a carbonate heavy, methacrylate copolymer dispersion, talc, a macrogoal 6000, the titan dioxide (E 17 1, gelatin.

Dosage form

Capsule kishechnorastvorimy.

Main physical and chemical properties:

Basis and cap of the capsule of pink color; the maintenance of the capsule are white or almost white granules.

Pharmacotherapeutic group

Means for treatment of a round ulcer and a gastroesophageal reflux disease. Inhibitors of a proton pomp. ATX A02B C05 code.

Pharmacological properties

Pharmacodynamics.

with a symptomatic gastroesophagal reflux in 5 days of intake of esomeprazole in a dose of 20 and 40 mg the size rn in a stomach remained With patients at the level of 4 during the average period which was respectively 13 and 17 h. At intake of esomeprazole in a dose of 20 mg the relative number of patients with whom size rn in a stomach remained at the level of 4 during at least 8; 12 and 16 h, 76 respectively made; 54 and 24%. The corresponding relative number of patients at administration of esomeprazole in a dose of 40 mg was 97; 92 and 56%.

When using AUC as the parameter characterizing concentration in blood plasma showed communication between slowing down of secretion of acid and systemic action.

Therapeutic effects of slowing down of secretion of acid. At use of the medicament Emanera in a dose of 40 mg the treatment a reflux esophagitis is noted approximately at 78% of patients in 4 weeks and at 93% of patients in 8 weeks. Week treatment by esomeprazole in a dose of 20 mg 2 times a day and the corresponding antibiotics successfully suppressed Helicobacter pylori approximately at 90% of patients.

In an uncomplicated ulcer of a duodenum after week treatment for destruction of this bacterium need to carry out further monotherapy by anti-secretory medicaments for effective healing of an ulcer and disappearance of symptoms.

Pharmacokinetics.

Absorption and distribution. Esomeprazole is unstable to effect of acid therefore granules in an enteric cover are applied to oral introduction. In the conditions of in vivo the extent of transformation into R-isomer is insignificant. Esomeprazole is quickly soaked up, and the C _max in blood plasma is reached in 1–2 h after introduction. The absolute bioavailability is 64% after single introduction in a dose of 40 mg and increases up to 89% after repeated introduction of 1 times a day. For esomeprazole in a dose of 20 mg the corresponding sizes are 50 and 68%. At healthy volunteers the distribution volume at an equilibrium state in blood plasma is about 0.22 l/kg of body weight. 97% of the entered esomeprazole dose contact proteins of blood plasma.

Metabolism and excretion. Esomeprazole completely turns with the participation of the enzymatic system of P450 (CYP) cytochrome. The most part of metabolism of esomeprazole depends on a polymorphic isoenzyme of CYP 2C19 which is responsible for formation of hydroxyl and desmetilovy metabolites of esomeprazole. The rest of metabolism depends on other specific isoenzyme of CYP 3A4 responsible for formation of an ezomeprazolsulfon — the main metabolite in blood plasma.

Indication

Gastroesophageal reflux disease:

• treatment erosive reflux esophagitis;
• long-term treatment for the purpose of prevention of a recurrence;
• symptomatic treatment of a gastroesophageal reflux disease.

In combination with antibacterial agents for Helicobacter pylori eradikation:

• treatment of an ulcer of the duodenum tied with Helicobacter pylori;
• prevention of a recurrence of a round ulcer at patients with the ulcer caused by Helicobacter pylori.

Treatment and prevention of the ulcers caused by prolonged use of NPVP:

• treatment of the ulcers caused by therapy of NPVP;
• prevention of stomach ulcers and a duodenum at patients of risk group in connection with use of NPVP.

Prevention of a recurrence of bleeding of stomach ulcer or a duodenum after treatment by esomeprazole in the form of solution for infusions.

Treatment of a syndrome of Zollinger — Ellisona.

Use

Capsule entirely, washing down with liquid. the medicament of an emaner can be taken at meal time or without it at any time. capsules cannot be chewed or crushed.

For patients, it is difficult for them to swallow, the capsule can be opened, and to dissolve granules and a half a glass of still water. Any other liquid is not recommended to be used because of possible dissolution of an enteric cover. Liquid with granules needs to be drunk at once or within 30 min. after preparation. After that it is necessary to rinse a glass with a half of a glass of water and to drink. Granules cannot be chewed or crushed.

For patients who cannot swallow the capsule needs to be opened, to dissolve granules and a half a glass of still water and to enter via the gastric tube. It is important to check carefully compliance of the chosen syringe and probe. Instructions for preparation and administration of solution are provided in the section SPECIAL INSTRUCTIONS.

Adults and children are aged more senior than 12 years

Gastroesophagal reflux:

• treatment erosive reflux esophagitis: 40 mg of 1 times a day daily during 4 weeks. For patients at whom the esophagitis is not cured or disease symptoms are noted, it is recommended to carry out additional 4 weeks treatment;
• long-term treatment of patients with the cured esophagitis for prevention of a recurrence: 20 mg of 1 times a day daily;
• symptomatic treatment of a gastroesophagal reflux: to patients without esophagitis — on 20 mg of 1 times a day daily. If in 4 weeks the symptoms did not disappear, it is necessary to perform additional examination of the patient. If symptoms disappeared, then it is possible to apply 20 mg of 1 times a day to further control daily. At adults it is possible to use the scheme of treatment as necessary at introduction of 20 mg of 1 times a day daily. For further control of symptoms at patients to whom carry out treatment of NPVP and note the increased risk of developing stomach ulcer and a duodenum, it is not recommended to apply the scheme of treatment "on demand".

Adult. In combination with the corresponding antibacterial schemes of treatment for destruction of Helicobacter pylori:

• treatment of an ulcer of the duodenum caused by Helicobacter pylori;
• prevention of a recurrence of stomach ulcer and a duodenum at patients with the ulcers caused by Helicobacter pylori.

On 20 mg of Emanera in a complex from 1 g of amoxicillin and 500 mg of a klaritromitsin 2 times a day within 7 days.

Patients who need continuous treatment of NPVP

• treatment of the stomach ulcer caused by use of NPVP: the usual dose makes 20 mg of 1 times a day. Treatment duration — 4–8 weeks;
• prevention of a recurrence of the stomach ulcer and a duodenum caused by treatment of NPVP at patients with high risk: 20 mg of 1 times a day.

Prevention of repeated bleeding of stomach ulcer after preliminary administration of esomeprazole: on 40 mg of 1 times a day daily during 4 weeks after introduction for prevention of a recurrence of bleeding of stomach ulcer and a duodenum.

Treatment at Zollinger's syndrome — Ellisona. The recommended initial dose of Emanera — on 40 mg 2 times a day. Later a dose it is possible to change and continue individually treatment according to clinical indications. On the basis of the available clinical data at most of patients the control at intake of esomeprazole in doses from 80 to 160 mg/days daily can be reached. At doses higher than 80 mg/days a dose should be divided into 2 receptions.

Children aged up to 12 years. Due to the lack of data Emanera is not recommended to be applied at treatment of children aged up to 12 years.

Contraindication

Hypersensitivity to active substance, the substituted benzimidazoles or any other ingredient of drug. esomeprazole, as well as other inhibitors of a proton pomp, it is not recommended to apply together with atazanaviry (see interactions). children's age up to 12 years.

Side effects

during clinical trials and after implementation of esomeprazole in broad medical practice it was reported about given below side effects. the dose-dependent effect is not revealed. the undesirable phenomena were classified by bodies and the systems of bodies.

within each frequency group in an order of reduction of their gravity.

Disturbance of indicators of blood and lymphatic system: leukopenia, thrombocytopenia, agranulocytosis, pancytopenia.

from the immune system: reactions of hypersensitivity, for example fever, Quincke's disease and anaphylactic reactions / shock.

from metabolism and digestion: peripheral hypostases, hyponatremia.

from mentality: insomnia, agitation, confusion of consciousness, depression, aggression, hallucinations.

from nervous system: headache, dizziness, paresthesias, drowsiness, disturbance of flavoring feelings.

from an organ of sight: illegibility of sight.

from an organ of hearing: vertigo.

from respiratory organs, a thorax and mediastinum: bronchospasm.

from digestive system: an abdominal pain, a constipation, diarrhea, a meteorism, nausea/vomiting, dryness in a mouth, stomatitis, gastrointestinal candidiasis.

from a gepatobiliarny system: increase in activity of enzymes of a liver, hepatitis with jaundice or without it, a liver failure, encephalopathy at patients with the liver disease which is available earlier.

from skin and hypodermic fabrics: dermatitis, an itching, rash, urticaria, baldness, photosensitivity, a multiformny erythema, Stephens's syndrome — Johnson, a toxic epidermal necrolysis.

from a musculoskeletal system and connective tissue: arthralgia, myalgia, muscle weakness.

from kidneys and urinary tract: interstitial nephrite.

from a reproductive system and mammary glands: gynecomastia.

System disturbances and reactions in the injection site: an indisposition, the increased sweating.

Special instructions

in the presence of any disturbing symptom (for example considerable inadvertent degrowth of a body, frequent vomiting, a dysphagy, a hematemesis or a melena) and also at existence or suspicion of stomach ulcer it is necessary to exclude a malignant disease as treatment of emanery can mask symptomatology and delay detection of a tumor.

to Patients to whom long-term treatment (is carried out especially at treatment within more than one year) needs to make regular observation.

Patients to whom treatment on demand is carried out have to see a doctor at once if the nature of symptoms changes. When prescribing esomeprazole for treatment on demand it is necessary to consider a possibility of interaction with other medicines owing to fluctuation of concentration of esomeprazole in blood plasma (see INTERACTIONS).

Introduction via the gastric tube

1. to Open the capsule and to gather granules in the corresponding syringe, and then to gain about 25 ml of water and about 5 ml of air in the syringe. For some probes it is necessary to prepare dispersion from 50 ml of water to prevent blockage of the probe granules.
2. to stir up the syringe for hypodispersion of granules in suspension At once.
3. Holding the syringe a tip up, to check that it was not corked.
4. to Attach the syringe to the probe, keeping the position of the syringe described above.
5. to Stir up the syringe and to turn it the end down. At once to enter 5–10 ml into the probe. After introduction to turn the syringe and to stir up (the syringe should be held the end up to avoid blockage).
6. to Turn the syringe the end down and at once to enter 5-10 more ml into the probe. To repeat this procedure before full depletion of the syringe.
7. to Gain 25 ml of water and 5 ml of air in the syringe and if necessary to repeat procedure No. 5 for washing away of the deposit which remained in the syringe. Some probes require 50 ml of water.

Use during pregnancy or feeding by a breast

obtained insufficient clinical data concerning effect of esomeprazole during pregnancy. At use of omeprazolum which is racemic mix the data obtained during the epidemiological researches for the bigger number of women during pregnancy do not indicate presence of the effects connected with a malformation or a fetotoksichnost. During the experiments on animals using esomeprazole data which would indicate existence of an adverse effect on development of an embryo/fruit are not obtained. During the experiments on animals using this racemic mix signs of direct or indirect adverse impact on a course of pregnancy, childbirth or postnatal development are noted. It is necessary to appoint this medicament pregnant with care.

whether esomeprazole gets into breast milk at women. Researches with participation of women during feeding by a breast were not conducted. Therefore medicament is not recommended to be used during feeding by a breast.

Children

due to the lack of data medicament is not recommended to be used for treatment of children aged up to 12 years.

No influence is revealed by

.

Interaction

As well as in case of use of other medicaments reducing intragastric acidity, absorption of such medicaments as ketokonazol, itrakonazol and also erlotinib can decrease whereas absorption of drugs, such as digoxin, can increase at use by esomeprazole and acetylsalicylic acid. Simultaneous use of omeprazolum (20 mg/days) and digoxin at healthy volunteers increased bioavailability of digoxin by 10% (at 2 of 10 people — for 30%).

Omeprazolum, as well as esomeprazole, works as CYP inhibitor 2C19. Use of omeprazolum in a dose of 40 mg by healthy volunteers during the research led to increase in the C _max and AUC for a tsilostazol respectively for 18 and 26%, and for one of its active metabolites — respectively for 29 and 69%.

At simultaneous use of esomeprazole it was reported about increase in level of a takrolimus in blood plasma.

It was reported about increase in level of a methotrexate in blood at some patients at a concomitant use with inhibitors of a proton pomp. If necessary to enter a methotrexate in high doses it is necessary to consider a question of temporary cancellation of esomeprazole.

omeprazolum Use (40 mg of 1 times a day) together with atazanaviry 300 mg and ritonaviry 100 mg at healthy volunteers led to significant weakening of action of an atazanavir (about 75% reduction of AUC, C _max , the C _min ). Increase in a dose of an atazanavir to 400 mg did not compensate influence of omeprazolum on efficiency of an atazanavir. Inhibitors of a proton pomp, including esomeprazole, should not be applied together with atazanaviry.

clinically significant effect on pharmacokinetics of amoxicillin or quinidine. At simultaneous short-term use of esomeprazole and Naproxenum or a rofekoksib of clinically significant pharmacokinetic interactions it was not noted.

Influence of other medicaments on esomeprazole pharmacokinetics. Esomeprazole is metabolized 2C19 and CYP 3A4. Simultaneous use of esomeprazole and CYP inhibitor 3A4 of a klaritromitsin (500 mg 2 times a day) led to increase in exposure of esomeprazole twice. Simultaneous use of esomeprazole and the combined inhibitor 2C19 and CYP 3A4, such as vorikonazol, can cause increase in exposure of esomeprazole in more than 2 times.

Overdose

Knows very few cases of deliberate overdose. gastrointestinal disorders and weakness were the symptoms described in connection with reception of a dose of 280 mg. single doses of esomeprazole of 80 mg did not cause disorders. specific antidote is unknown. esomeprazole well contacts proteins of blood plasma and therefore it is badly removed by dialysis. at overdose it is necessary to carry out symptomatic treatment and to take standard measures for maintenance of functions of an organism.

Storage conditions

At a temperature not above 30 °C.