Omeprazol

General characteristics. Structure:

Active ingredient: 20 mg of an omeprazol (in the form of pellets of an omeprazol of 8,5%) in each capsule.

Structure of pellets: Omeprazola-8,5 g, excipients: dinatrium hydroortho-phosphate, sodium lauryl sulfate, calcium carbonate, sugar, Mannitolum, gidroksipropilmetiltsellyuloza-E5, copolymer of methacrylic acid, diethyl phthalate, talc, titanium dioxide.

Structure of the capsule: gelatin, glycerin, нипагин, нипазол, sodium lauryl sulfate, the water purified titanium dioxide.

Pharmacological properties:

Pharmacodynamics. Omeprazol has anti-secretory and antiulcerous effect.

The mechanism of action is connected with ability of an omeprazol to block operation of the "proton" pump N +/K+-Atfazy. After intake the capsule of an omeprazol is dissolved in acid contents of a stomach and releases pellets (microgranule). Pellets come to a duodenum where in the alkaline environment allocate омепразол. After absorption, with a blood flow омепразол comes to a mucous membrane of a stomach and a gleam of tubules of covering cells where there is acid medium (рН <3,0), is oxidized in an active form – sulphenamide-omeprazola (SA-O). SA-O connects SH groups N +/K+-Atfazy in tubules of covering cells and is irreversible blocks enzyme work. It leads to disturbance of the last stage of process of formation of hydrochloric acid of a gastric juice.

Omeprazol дозозависимо reduces the level of basal (natoshchakovy) and stimulated (postprandialny) secretion of a gastric juice. Reduces the total amount of gastric secretion, release of pepsin. Effectively oppresses both a night, and day kislotoproduktion.

After a single dose in a dose of 20 mg the effect occurs within the first hour and reaches a maximum in 2 h. Oppression of stimulated secretion for 50% remains during 24 h, at the same time level intragastric рН> 3,0 remains during 17 h. Stable decrease in secretion develops by 4th day of therapy. Ability of covering cells to produce hydrochloric acid is recovered in 2 - 3 days after the termination of reception of an omeprazol.

Omeprazol concentrates in covering cells of glands of a stomach and has cytoprotective effect (stimulates secretion of slime and bicarbonates, reproduction of cells of an epithelium, interferes with the return diffusion of protons from a stomach gleam in its mucous).

Has bactericidal effect on Helicobacter pylori (the size of the minimum overwhelming concentration makes 25 - 50 mkg/ml), raises a susceptibility of bacteria to antibiotics and eradikatsionny therapy. The Antigelikobakterny combinations of antibiotics including омепразол provide an eradikation of a bacterium not less than in 85%.

At treatment of an ulcer of a duodenum within 4 weeks scarring of an ulcer happens at 93% of patients, at treatment of stomach ulcer within 8 weeks this indicator makes 96%, scarring of round ulcers of a gullet is reached at 90% of patients.

Pharmacokinetics. After intake it is quickly and almost completely absorbed in the digestive tract (DT). Bioavailability makes 30 - 40% owing to effect of "the first passing" through a liver. After reception in a dose of 40 mg the maximum concentration in plasma makes 1,26  0,41 mkg/ml and is reached in 1,38  0,32 h. At repeated introductions, due to oppression of own metabolism absorption of an omeprazol increases, and its bioavailability increases.

In blood is for 95% in the state connected with proteins of plasma (albumine, acid α1-гликопротеин). The volume of distribution makes 0,2 - 0,5 l/kg.

It is metabolized in a liver with the participation of P450 CYP2D19 cytochrome with formation of 6 inactive metabolites: гидроксиомепразол, sulphidic and sulfonic derivatives of an omeprazol. R-enantiomer of an omeprazol at the same time acts as inhibitor of own metabolism, reducing activity of CYP2D19. In the European population of 3 - 5% of people have defective genes of CYP2D19 and slowly metabolize омепразол. In Asian population the share of slow metabolizator is 4 times higher.

It is excreted generally by kidneys in the form of metabolites (72 - 80%) and through intestines (18 - 23%). The general clearance makes 7,14 - 8,57 ml/min. The semi-elimination period at people with normal function of a liver of 0,5 - 1 h, at a chronic liver failure it can increase to 3 h. At a chronic renal failure elimination of an omeprazol decreases in proportion to decrease in clearance of creatinine.

At patients of advanced age delay of metabolism of an omeprazol and increase in its bioavailability is possible.

Indications to use:

- NPVS-gastropathy;

- peptic ulcer of a stomach and duodenum (treatment and prevention of a recurrence);

- gastroezofagelny reflux disease;

- hyper secretory states (Zollinger-Ellison's syndrome, stressful ulcers, polyendocrine adenomatosis, system mastocytosis);

- acute pancreatitis (for switching off of secretion of a pancreas);

- eradikatsionny therapy of Helicobacter pylori at the infected patients with a peptic ulcer of a stomach and duodenum (as a part of a combination therapy).

Route of administration and doses:

Apply inside preferably in the morning before food, without chewing, without crushing and without damaging the capsule, washing down with a small amount of water.

To adults and children at an aggravation of a peptic ulcer of a duodenum appoint in a dose 20 mg (1 capsule) of 1 times a day within 2 - 4 weeks.

At an aggravation of a peptic ulcer of a stomach and a gastroesophageal reflux disease, the NPVS-gastropathy appoint 20 mg (1 capsule) of 1 times a day within 4 - 8 weeks.

For an eradikation of Helicobacter pylori appoint 20 mg (1 capsule) 2 times a day within 7-14 days (depending on the applied scheme of an eradikation).

For prevention of aggravations of a peptic ulcer of a stomach and a duodenum appoint inside 10-20 mg courses for 2-4 weeks 2 times a year once a day (at the seasonal course of a disease) or it is continuous.

At Zollinger-Ellison's syndrome the dose is selected individually, depending on the initial level of gastric secretion. At adequately picked up dose the level of secretion should not exceed 10 mmol of acid/h or 5 mmol of acid/h after a stomach resection. Usually treatment begin 60 mg/days (3 capsules) with a dose, raising if necessary to 80 - 120 mg/days (4 - 6 capsules) in 2 - 3 receptions. Long administration of drug is possible (up to 5 years).

The maximum single dose of 40 mg, the maximum daily dose – 120 mg. At patients with a heavy liver failure the daily dose should not exceed 20 mg (1 capsule).

Features of use:

Pregnancy and lactation. It is contraindicated at pregnancy. Use during pregnancy is possible only according to vital indications. In need of use in the period of a lactation it is necessary to stop breastfeeding for all the time of treatment.

Use in pediatrics. Experience of use of an omeprazol for children is aged younger than 5 years is limited. Use of an omeprazol for this age group of patients is possible according to vital indications.

Influence on ability to driving of motor transport and control of mechanisms. Reception of an omeprazol does not affect ability of the patient to control of the vehicle or other operator activity.

Care when using. Before use of an omeprazol it is necessary to exclude existence of malignant process (especially at a peptic ulcer of a stomach) since masking of symptomatology and difficulty directed by the correct diagnosis is possible.

Difficulties using. At emergence of difficulties with a proglatyvaniye of the whole capsule, it is possible to swallow its contents after opening and preparation of mix with slightly acidified liquid (juice, yogurt, sour cream). The received mix should be used within 30 min.

Long continuous therapy. Long continuous antirecurrent therapy omeprazoly is shown to patients with endoscopic the proved III-IV stage of a gastroesophageal reflux disease (GERB) on Savary-Miller, at GERB complication (Barrett's gullet, a stricture or an ulcer of a gullet), reception of the medicines reducing a tone of the lower esophageal sphincter at the II stage of GERB on Savary-Miller at 2 aggravations in the anamnesis, at low indicators of basal pressure in the field of the lower esophageal sphincter.

Side effects:

- nausea, vomiting, abdominal pains, diarrhea or lock, meteorism; extremely seldom – increase in activity of transaminases, taste disturbance, dryness in a mouth, stomatitis.

- atrophic gastritis.

- hepatitis and abnormal liver functions (at patients with previous liver pathology).

- headache, dizziness, depression, excitement, encephalopathy.

- skin rash, small tortoiseshell, skin itch, Quincke's disease, fever, bronchospasm, acute anaphylaxis.

- photosensitization, mnogoformny exudative erythema (Sindromstivensa-Johnson), alopecia.

- hamaturia, proteinuria, intersticial nephrite.

- leukopenia, thrombocytopenia, eosinopenia, agranulocytosis, pancytopenia.

- arthralgias, muscular weakness, mialgiya.

- dryness in a mouth, hypersecretion of nasal slime, a dysuria.

- weakness, headache.

- in isolated cases: gynecomastia, peripheral hypostases, sweating strengthening, irreversible vision disorder.

- formation of gastric glandulyarny cysts, a hyperplasia of covering cells at prolonged use (have high-quality reversible character).

Interaction with other medicines:

At simultaneous use with antiacid means of clinically significant interactions it is noted.

Slows down absorption of medicines which depends from рН – ampicillin, an itrakonazol, a ketokonazol, iron preparations.

Slows down elimination and strengthens effect of the medicines which are metabolized CYP2D19 cytochrome – warfarin, diazepam, Phenytoinum.

Klaritromitsin and омепразол at combined use mutually increase concentration of each other and strengthen antigelikobakterny action.

Strengthens gematotoksichesky effect of chloramphenicol, Thiamazolum (mercazolil), lithium drugs.

Contraindications:

- hypersensitivity to an omeprazol;

- pregnancy or lactation.

Overdose:

Omeprazol possesses a hypotoxicity. At use in doses to 270 mg/days омепразол did not cause development of intoxication. At patients with a heavy liver failure at introduction in extremely high doses development of confusion of consciousness, an illegibility of sight, drowsiness, dryness in a mouth, a headache, nausea, tachycardias, arrhythmias is possible.

The specific antidote does not exist. Measures of the help include the drug withdrawal supporting and the symptomatic therapy directed to elimination of the arisen disturbances. The hemodialysis is insufficiently effective.

Storage conditions:

List B. In the place protected from light and moisture, at a temperature not over 25 ºС. To store in the place, unavailable to children. A period of validity - 2 years. Not to use medicine after the termination of a period of validity.

Issue conditions:

According to the recipe

Packaging:

On 10 capsules in a blister strip packaging, on the 3rd blister strip packagings in a pack from a cardboard.