Structure

Active ingredient: esomeprazole;

1 tablet, coated, contains esomeprazole of magnesium of trihydrate is equivalent esomeprazole of 20 mg or 40 mg

Excipients: microcrystalline cellulose, Natrii hydrocarbonas, silicon dioxide colloidal, krospovidon, magnesium stearate, talc

Cover (opadray white 58901 (Opadry White), povidone (K-30), talc, ferrous oxide yellow (E172) - is available in tablets, film coated, 20 mg, ferrous oxide red (E172) - is available in tablets, film coated, 40 mg, fragrance mint).

Dosage form

Tablet, film coated.

Main physical and chemical properties: oval, biconvex tablets, film coated pink (for 40 mg) or light yellow (for 20 mg) colors, with a notch for division on the one hand.

Pharmacological group

Means for treatment of a peptic ulcer and a gastroesophageal reflux disease. Inhibitors of the proton pump. Esomeprazole. ATX A02B C05 code.

Pharmacological properties

Pharmacodynamics

After oral administration of 20 mg and 40 mg of esomeprazole action comes within an hour. After repeated use of 20 mg of esomeprazole of 1 times a day within 5 days the average peak of emission of acid after stimulation by Pentagastrinum decreases by 90% when determining this indicator in 6–7 h after reception of a dose for the 5th day.

In 5 days of intake of esomeprazole on 20 mg and 40 mg higher than 4 during 13 both 17 h respectively and more than 24 h patients have with symptomatic a reflux esophagitis. A share of patients who had higher than 4 pH level of a stomach during 8; 12 and 16 h after reception of 20 mg of esomeprazole, were made respectively by 76; 54 and 24%. The corresponding proportions for esomeprazole of 40 mg made 97; 92 and 56%.

When using AUC as an indirect indicator of plasma concentration showed dependence of suppression of secretion of acid on medicament exposure.

Therapeutic effects of suppression of secretion of hydrochloric acid. Treatment a reflux esophagitis was esomeprazole of 40 mg successful approximately at 70% of patients after 4 weeks of treatment and at 93% — after 8 weeks of treatment.

Pharmacokinetics.

Absorption of esomeprazole happens quickly, peak concentration in blood plasma are reached approximately in 1–2 h after reception of a dose. The absolute bioavailability is 64% after use of a single dose of 40 mg and increases up to 89% after repeated use of 1 times a day. For 20 mg of esomeprazole the corresponding values 50 and 68 of %.

and reduces esomeprazole absorption, however it does not affect effect of esomeprazole concerning acidity in a gastric cavity.

Distribution. Distribution volume at healthy volunteers in equilibrium state is 0.22 l/kg of body weight. Esomeprazole for 97% contacts proteins of blood plasma.

Metabolism. Esomeprazole is completely metabolized by means of the system of cytochrome 450 (CYP). The main part of metabolism of esomeprazole depends on the polymorphic CYP 2C19 which is responsible for formation of hydroxy - and esomeprazole dezmetilmetabolit. Other part depends on the second specific isoform, CYP 3A4 causing formation of an ezomeprazolsulfon — the main metabolite in blood plasma.

Removal. The parameters specified below mainly reflect pharmacokinetics at persons with functional CYP enzyme 2C19 (extensive metabolizator).

Children. After repeated use of 20 mg and 40 mg of esomeprazole the systemic effect and time of achievement of the C _max medicament in blood plasma at children at the age of 12–18 years were same, as at adults.

Gender features. After a single dose of esomeprazole of 40 mg the average AUC value at women is 30% higher in comparison with men. No difference connected with a floor was noted at repeated administration of medicament of 1 times a day. These results do not influence an esomeprazole dosage.

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.

with antibacterial agents for Helicobacter pylori eradikation:

• treatment of an ulcer of the duodenum tied with Helicobacter pylori;
• prevention of a recurrence of round ulcers at patients with the ulcers 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 reception of NPVP.

Prevention of a recurrence of a helcomenia of a stomach or a dvenadtsatipersty gut later in/in treatments by esomeprazole.

Treatment of a syndrome of Zollinger — Ellisona.

Use

to use Drug inside to adults and children 12 years are aged more senior. to take a pill whole for 1 h to food, washing down with enough water. tablets should not be chewed or crushed. usually duration of a course of treatment is determined by the doctor.

Adults and children are aged more senior than 12 years. Gastroesophageal reflux disease: treatment erosive reflux esophagitis: 40 mg of 1 times a day during 4 weeks. Additional 4 weeks are recommended for patients with not cured esophagitis or its remained symptoms.

Long-term treatment for the purpose of prevention of a recurrence: 20 mg of 1 times a day.

Symptomatic treatment of a gastroesophageal reflux disease: 20 mg of 1 times a day to patients without esophagitis. If control of symptoms is not reached during 4 weeks of treatment, the patient needs to be examined. At elimination of symptoms their further control can be reached at reception of 20 mg of 1 times a day. It is possible to apply the scheme "in case of need" which provides reception of 20 mg of 1 times a day to adults. Further control of symptoms with use of the scheme "in case of need" is not recommended to the patients applying NPVP and which have a risk of developing stomach ulcer or a duodenum.

Adult. Treatment of an ulcer of the duodenum tied with Helicobacter pylori: 20 mg of esomeprazole from 1 g of amoxicillin and 500 mg of a klaritromitsin 2 times a day within 7 days.

Prevention of a recurrence of round ulcers at patients with the ulcers caused by Helicobacter pylori: 20 mg of esomeprazole from 1 g of amoxicillin and 500 mg of a klaritromitsin 2 times a day within 7 days.

Treatment of the stomach ulcers associated with treatment of NPVP: the recommended dose — 20 mg of 1 times a day. Duration of treatment is 4–8 weeks

Prevention of the stomach ulcers and a duodenum associated with treatment of NPVP at patients of risk group: the recommended dose makes 20 mg of 1 times a day.

Prevention of a recurrence of bleeding of stomach ulcer or a duodenum later in/in treatments by esomeprazole: 40 mg of 1 times a day during 4 weeks. The therapy directed to oppression of acidity which consists in use of esomeprazole in the form of solution for infusions has to precede the period of intake of esomeprazole.

Contraindication

Known hypersensitivity to esomeprazole, the substituted benzimidazoles or other components of drug. simultaneous use with atazanaviry, nelfinaviry.

Side effects

during clinical trials and after implementation of esomeprazole in broad medical practice it was reported about the side effects given below. the dose-dependent effect is not revealed. the undesirable phenomena were classified depending on emergence frequency: often (1/100, 1/10); infrequently (1/1000, 1/100); seldom (1/10,000, 1/1000) and it is very rare (1/10,000).

from blood and lymphatic system: seldom — a leukopenia, thrombocytopenia; very seldom — an agranulocytosis, a pancytopenia.

from the immune system: seldom — reactions of hypersensitivity, including fever, a Quincke's disease, anaphylactic reactions / shock.

from a metabolism and food: infrequently — peripheral hypostases; seldom — a hyponatremia; very seldom — a hypomagnesiemia; the heavy hypomagnesiemia can lead to a hypocalcemia.

Disturbance of mentality: infrequently — insomnia; seldom — excitement, a depression, confusion of consciousness; very seldom — aggression, hallucinations.

from nervous system: often — a headache; infrequently — dizziness, weakness, paresthesias, drowsiness; seldom — disturbance of taste.

from an organ of sight: seldom — illegibility of sight.

from an organ of hearing and labyrinth disturbances: infrequently — vertigo.

from the respiratory system, bodies of a thorax and mediastinum: seldom — a bronchospasm.

from a digestive tract: often — an abdominal pain, a constipation, diarrhea, an abdominal distension, nausea, vomiting; infrequently — dryness in a mouth; seldom — stomatitis, GIT candidiasis; very seldom — microscopic colitis.

from a gepatobiliarny system: infrequently — increase in level of liver enzymes; seldom — hepatitis with or without jaundice; very seldom — a liver failure, encephalopathy at patients with liver diseases.

from skin and hypodermic fabrics: infrequently — dermatitis, an itching, urticaria, rash; seldom — an alopecia, a photosensitization; very seldom — a multiformny erythema, Stephens's syndrome — Johnson, a toxic epidermal necrolysis.

from musculoskeletal and connective tissue: infrequently — a fracture of a hip, wrist or backbone (see. Special INSTRUCTIONS); seldom — an arthralgia, myalgia; very seldom — muscle weakness.

from kidneys and an urinary system: very seldom — interstitial nephrite (at some patients — along with a renal failure).

from a reproductive system and mammary glands: very seldom — a gynecomastia.

General disorders and disturbances in the injection site: seldom — weakness, the increased sweating.

Special instructions

in the presence of symptoms (for example the significant degrowth of a body, nausea, a dysphagy, gematemez or a melena) and in cases when it is predicted or diagnosed stomach ulcer, malignant pathology as use of esomeprazole can change symptoms has to be excluded and delay establishment of the correct diagnosis.

Patients using medicament for a long time (especially it is more than a year), have to be under regular observation.

to the doctor about changes of nature of symptoms.

When prescribing esomeprazole for an eradikation of Helicobacter pylori needs to consider possible medicinal interactions of all components of triple therapy. Klaritromitsin is powerful CYP inhibitor 3A4, and it is necessary to consider its contraindications and interactions (if triple therapy at the patients accepting along with esomeprazole other medicines which are metabolized by CYP 3A4, such, for example, as tsizaprid is performed).

Use during pregnancy and feeding by a breast

pregnancy Period. Clinical data on use of esomeprazole for treatment of pregnant women are limited.

absence malformatsionny (fetation disturbance) and fetotoksichesky effects. Esomeprazole researches on animals did not reveal direct or indirect negative impact on development of an embryo/fruit. The research of racemic mix on animals did not show direct or indirect negative impact on pregnancy, childbirth and post-natal development. To appoint medicament during pregnancy with care.

feeding Period breast. Researches with the assistance of the women nursing are not conducted. It is unknown whether esomeprazole gets into breast milk. Therefore esomeprazole should not be applied during feeding by a breast.

Fertility. Researches of racemic mix of omeprazolum on animals did not show influence on fertility.

Children

use Drug at children aged 12 years are more senior.

Ability to influence speed of response at control of vehicles or work with other mechanisms

Drug does not influence speed of response at control of vehicles or work with other mechanisms. In case of development of dizziness and/or illegibility of sight it is necessary to refrain from control of vehicles or other mechanisms.

Interaction

Vorikonazol. Omeprazolum, as well as esomeprazole, works as CYP inhibitor 2C19. Simultaneous use of omeprazolum (40 mg of 1 times a day) led to increase in the C _max and AUC for a vorikonazol (CYP 2C19-substrate) for 15 and 41% respectively.

Diazepam. Simultaneous use of 30 mg of esomeprazole leads to decrease in clearance of CYP 2C19-substrate of diazepam by 45%.

Klopidogrel. At healthy faces it was noted pharmacokinetic / pharmakodinamicheskoye interaction between klopidogrely (a load dose of 300 mg / a daily maintenance dose of 75 mg) and esomeprazole (40 mg/days inside) that led to reduction of exposure of an active metabolite klopidogrelya on average for 40% and to reduction of the maximum inhibiting activity (ADF-indutsirovannoy) concerning aggregation of thrombocytes on average for 14%.

Methotrexate. It was reported about increase in level of a methotrexate in blood of some patients at a concomitant use with IPP. In case of need introductions of a methotrexate in high doses it is necessary to consider a question of temporary cancellation of esomeprazole.

Takrolimus. At simultaneous use of esomeprazole it was reported about increase in level of a takrolimus in blood plasma. In case of use of this combination it is necessary to carry out monitoring of function of kidneys (clearance of creatinine), monitoring of level of a takrolimus in blood plasma and if necessary to make dose adjustment.

Tsizaprid. Healthy volunteers have a simultaneous use of 40 mg of esomeprazole with tsizapridy leads to increase in AUC by 32% and increase in T _½ for 31%, but there was no noticeable increase in peak level of a tsizaprid in blood plasma. Moderately prolonged Q-T-interval was noted after reception of a tsizaprid separately and did not increase at further use of a tsizaprid in a combination with esomeprazole.

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

Phenytoinum. Simultaneous use of 40 mg of esomeprazole leads to increase in level of Phenytoinum in blood plasma for 13% at patients with epilepsy. It is recommended to control concentration of Phenytoinum in blood plasma at appointment or cancellation of therapy as esomeprazole.

clinically significant effect on pharmacokinetics of amoxicillin or quinidine.

overdoses Given relatively are limited to

. gastrointestinal symptoms and weakness are described after intake of esomeprazole in a dose of 280 mg. the single dose of esomeprazole of 80 mg will not cause heavy side effects. special antidote is unknown. esomeprazole substantially contacts proteins of blood plasma therefore it is not removed by means of dialysis.

Treatment: symptomatic and maintenance therapy.

Storage conditions

In original packing at a temperature not above 25 °C.