Beret - instructions for use, dose, side effects, contraindications

Name	One tablet of 10 mg	One 20 mg tablet
Active substance
Rabeprazole sodium	10.0 mg	20.0 mg
Excipients: for the preparation of a core tablet	100.0 mg	200.0 mg
Mannitol (Mannogem EZ Spray Dried)	28.0 mg	56.0 mg
Giprolase low-substituted (L-HPC)	13.0 mg	26.0 mg
Giprolosa (Klucel)	4.0 mg	8.0 mg
Magnesium oxide (Marinco HE)	44.0 mg	88.0 mg
Magnesium stearate	1.0 mg	2.0 mg
Auxiliary substances for the inner shell (sublayer)
Ethyl cellulose	1.0 mg	2.0 mg
Magnesium oxide (Marinco HE)	1.0 mg	2.0 mg
Auxiliary substances: to prepare a tablet coated with enteric coating, bulk	118.0 mg	236.0 mg
Acrylic-from pink [Copolymer of methacrylic acid	14.72 mg
Talc Titanium dioxide Sodium bicarbonate Sodium lauryl sulfate Aluminum lacquer based on dye azorubin Aluminum lacquer based on the sunset yellow dye] Acrylic - from yellow [Copolymer of methacrylic acid Talc Titanium dioxide Silica colloidal dioxide Sodium bicarbonate Sodium lauryl sulfate Dye iron oxide yellow] Triethyl citrate	= = = 1.28 mg	29.44mg 2.56 mg

Description:

Dosage of 10 mg:

round biconvex tablets, coated with a coat of light pink to reddish-pink.

On the cross-section the nucleus is white or white with a yellowish tint of color.

Dosage of 20 mg:

round biconvex tablets, coated with a coating of light yellow to yellow.

On the cross-section the nucleus is white or white with a yellowish tint of color.

Pharmacotherapeutic group:a drug that reduces the secretion of the glands of the stomach - the proton pump inhibitor.

ATX: & nbsp

A.02.B.C Proton pump inhibitors

A.02.B.C.04 Rabeprazole

Pharmacodynamics:

Rabeprazole sodium belongs to the class of antisecretory compounds, which in chemicalichIn other respects they are substituted benzimidazoles.The drug depresses the activesoutThe enzyme H + / K +-ATPase, thereby blocking the final stage of the synthesis of hydrochloric acid. This effect is dose-dependent and leads to theftthe basal as well as the stimulated secretion of hydrochloric acid irrespective of the stimulus. As a weak foundation rabeprazole in any doses is rapidly adsorbed and concentrated in the acidic environment of parietal cells.

Antisecretory activity. After oral administration of 20 mg of rabeprazole, the antisecretory effect occurs within one hour. Oppression of basal and stimulated secretion of hydrochloric acid 23 hours after the first dose of rabeprazole sodium is 69 and 82%, respectively, and lasts up to 48 hours. This duration of pharmacokinetic effect is much higher than the predicted half-life (approximately 1 hour). This effect can be explained by the long-term binding of the drug substance to H⁺/TO⁺ATPase of parietal cells of the stomach. The magnitude of the inhibitory effect of rabeprazole sodium on acid secretion reaches a plateau after three days of taking rabeprazole sodium. At the termination of reception of secThe retor activity is restored during 1-2 days.

Effect on the concentration of gastrin in serum. At the beginning of therapy with rabeprazoleMr.the concentration of gastrin in the serum increases, which is a reflection of the inhibitory effect on the secretion of hydrochloric acid. The concentration of gastrin returns to the originalolevel usually during 1-2 weeks after discontinuation of treatment.

Effect on enterochromafin-like cells

When examining samples of a human stomach biopsy from the antrum and stomach bottom, 500 patients who received rabeprazole sodium or a reference preparation for up to 8 weeks, stable changes in the morphological structure of enterochroma- phin-like cells, the degree of gastritis, the frequency of atrophic gastritis, intestinal metaplasia, or the spread of infection Helicobacter pylori were not revealedthewives.

In a study involving more than 400 patients who received rabeprazole sodium (10 mg / day or 20 mg / day) up to 1 year, the incidence of hyperplasia was low and comparable to that of omeprazole (20 mg / kg). No case of adenomatous changes or carcinoid tumors observed in rats was recorded.

Other effects. Currently, there is no evidence that rabeprazole causes systemic effects from the central nervous system, cardiovascular and respiratory systems. When administered orally, 20 mg for 2 weeks rabeprazole does not affect the function of the thyroid gland, the metabolism of carbohydrates, and also at the endMr.trait in the blood of parathyroid hormone, cortisol, estrogens, testosterone, prolactin, secretin, glucagon, follicle-stimulating hormone, luteinizing hormone, renin, aldosterone and growth hormone.

Pharmacokinetics:

Absorption is high, the time to reach the maximum concentration TSam - 3.5 hours. Changes in maximum concentration (Сmах) and the values of the area under the curve "concentration-time" (AUC) are linear in the dose range of 10 to 40 mg. Metabolized in the liver with the participation of isoenzymes CYP2C9 and CYP3A. Bioavailability - 52%, does not increase with multiple admission. The half-life of T1 / 2 is 0.7-1.5 hours, the total clearance is 3.8 ml / min / kg. In patients with hepatic insufficiency AUC increases by 2 times, T1 / 2 - increases by 2-3 times. Neither the time of taking the drug during the day, nor antacids affect the absorption of rabeprazole. Taking the drug with fatty foods slows the absorption of the drug for 4 hours or more, but neither Сmах, nor the degree of absorption is changed.

The connection with plasma proteins is 97%. It is excreted by the kidneys - 90% in the form of 2 metabolites: a conjugate of mercapturic acid (M5) and carboxylic acid (M6); through the intestine - 10%. There are no differences in pharmacokinetic parameters depending on sex.

Renal insufficiency

In patients with stable renal insufficiency in the terminal stage, which require maintenance hemodialysis (creatinine clearance> 5ml / min / 1.73m²) the finding of rabeprazole sodium is similar to that of healthy volunteers. AUC and Сmах in these patients were approximately 35% lower than in healthy volunteers. On average, the half-life of rabeprazole was 0.82 hours in healthy volunteers, 0.95 hours in patients during hemodialysis and 3.6 hours after hemodialysis. The clearance of the drug in patients with kidney disease requiring hemodialysis was approximately twice that of healthy volunteers.

Liver failure

Patients with chronic compensated cirrhosis transfer rabeprazole in a dose of 20 mg once a day, although AUC doubled and Сmах increased by 50% compared to healthy volunteers.

Elderly patients

In elderly patients, the elimination of rabeprazole is somewhat slowed down. After 7 days of taking rabeprazole 20 mg per day in the elderly AUC was about twice as large, and Сmах increased by 60% compared to young healthy volunteers. However, there were no signs of cumulation of rabeprazole.

CYP2CI9 polymorphism

In patients with delayed metabolism CYP2C19 after 7 days of taking rabeprazole at a dose of 20 mg per day AUC increases by 1.9 times and T1 / 2 - by 1.6 times by comparison of the same parameters for "fast metabolizers", while Сmах increases by 40%.

Indications:

Peptic ulcer of the duodenum intestines in the stage of exacerbation;
Stomach ulcer in the stage of exacerbation and ulcer of anastomosis;
Erosive and ulcerative gastroesophageal reflux disease (GERD) or reflux esophagitis;
Supportive therapy of GERD;
Non-erosive reflux disease (NERD);
Zollinger-Ellison syndrome or other conditions characterized by pathological hypersecretion.

In the combination therapy:

Eradication N. pylori in patients with peptic ulcer and duodenal ulcer or chronic gastritis;

Treatment and prevention of relapse of peptic ulcer associated with Helicobacter pylori.

Contraindications:

Hypersensitivity to rabeprazole or the components of the drug, pregnancy, lactation, children's age to 12 years.

Carefully:

Severe renal, severe hepatic insufficiency.

Pregnancy and lactation:

There are no data on the safety of rabeprazole during pregnancy. Isledovenreproductive activity in rats and rabbits showed no signs of impaired fertilityьнor fetal developmental defects due to rabeprazole; however, rats infuckThe drug penetrates through the placental barrier. Rabeprazole do not cryunitsIt should be used during pregnancy, except when the expected positive effect for the mother exceeds the possible harm to the fetus. It is not known, stands out whether rabeprazole with breast milk. Appropriate studies in lactating women were not conducted. At the same time rabeprazole It is found in the milk of lactating rats, so the drug can not be used by nursing women.

Dosing and Administration:

Tablets are taken internally as a whole, without chewing or grinding.

With peptic ulcer in the stage of exacerbation and ulcer of anastomosis it is recommended to take inside 10 mg or 20 mg 1 time per day. The course is 6 weeks, in some cases the duration of therapy can be increased by 6 weeks.

With duodenal ulcer in the acute stage it is recommended to take 10 mg 1 time or 20 mg once a day. Duration of treatment - 2 - 4 weeks. The duration of treatment can be continued for another 4 weeks.

With gastroesophageal reflux disease (GERD) and reflux esophagitis it is recommended to take 10 mg or 20 mg once a day for 4-8 weeks; If necessary, treatment can be continued for another 8 weeks.

For maintenance therapy with GERD the drug is used at a dose of 10 mg or 20 mg once a day, depending on the response to treatment. The duration of treatment depends on the patient's condition.

With non-erosive gastroesophageal reflux disease NERD without esophagitis the drug is used at a dose of 10 mg or 20 mg once a day for 4 weeks; if after 4 weeks of treatment the symptoms do not disappear, an additional examination of the patient should be carried out; after relief of symptoms to prevent their subsequent occurrence should take the drug in a dose 10 mg 1 once a day on demand.

For the treatment of Zollinger-Ellison syndrome and other conditions characterized by pathological hypersecretion, the dose is selected individually. The initial dose is 60 mg per day, then the dose is increased and the drug administered in a dose up to 100 mg per day for a single dose or 60 mg twice a day. Treatment should continue as clinical necessity, sometimes to 1 of the year;

To eradicate N. pylori take 20 mg 2 times a day, using the appropriate combination of antibiotics. Duration of treatment is 7 days.

Patients with renal and hepatic insufficiency Correction of the dose for renal failure is not required.

With a mild and moderate degree of hepatic insufficiency, the concentration of rabeprazole in the blood is higher than in healthy volunteers. Care should be taken when using the drug in patients with severe hepatic impairment.

Children

The recommended dose for children aged 12 years and over is 20 mg once a day, up to 8 days.

Side effects:

Rabeprazole is usually well tolerated by patients. Side effects are mild and transient.

Classification of the incidence of adverse events (WHO):

very often (> 1 /10), often (from> 1/100 up to < 1/10), infrequently (from> 1/1000 up to < 1 /100), rarely (from>1/10 000 up to < 1/1000), very rarely (from < 1/10 000), including individual messages.

From the gastrointestinal tract: often - constipation, diarrhea, abdominal pain, dryness of the oral mucosa, flatulence; rarely - hepatitis, jaundice, in patients with cirrhosis - hepatic encephalopathy.

From the nervous system: infrequently - headache, dizziness.

From the laboratory indicators: rarely - thrombocytopenia, neutropenia, leukopenia, leukocytosis, increased activity of hepatic enzymes.

From the musculoskeletal system: rarely - myalgia, arthralgia.

From the skin: rarely - hives, bullous eruptions; very rarely - erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome.

From the side of the kidneys: very rarely - interstitial nephritis.

Overdose:

It was reported that rabeprazole was taken at a dose of 60 mg 2 times a day or 160 mg once, while the side effects were minimal and reversible and did not require medical intervention.

Treatment: conducting symptomatic and maintenance therapy. There is no specific antidote. Rabeprazole binds well to plasma proteins, so it is poorly removed by dialysis.

Interaction:

Rabeprazole, like other inhibitors of the proton pump (IPN), is metabolized with the participation of the cytochrome P450 system (CYP450) in the liver. Rabeprazole does not enter into clinically significant interactions with amoxicillin and with other drugs metabolized by the cytochrome P450 system-warfarin, phenytoin, theophylline, and diazepam. Due to rabeprazole causes a pronounced and prolonged decline in the production of hydrochloric acid, there was an interaction with simultaneous reception with drugs, the absorption of which depends on the acidity of the contents of the stomach. In healthy volunteers, the use of rabeprazole caused a decrease in the concentration of ketoconazole in the blood plasma by 30% and an increase in the minimum digoxin concentration by 22%. With simultaneous reception of Beret's drug with these drugs, it is necessary to adjust the dose of ketoconazole or digoxin.

With the simultaneous administration of atazanavir 300 mg / ritonavir 100 mg with omeprazole (40 mg once a day) or with atazanavir 400mg with lansoprazole (60 mg once daily) with healthy volunteers, a significant reduction in the effect of atazanavir was observed. Atazanavir absorption is pH dependent. Thus, concurrent administration of atazanavir with proton pump inhibitors is not recommended, including rabeprazole.

Concentrations of rabeprazole and the active metabolite of clarithromycin in plasma at oneabelt admission increases by 24% and 50% respectively. This effectuzuduring eradication. pylori. There was no interaction of rabeprazole with liquid antacids. In addition, there was no clinically significant interaction of rabeprazole with food. At expected concentrations in the blood plasma rabeprazole does not have a stimulating or initiating influence on the metabolism CYP3A4. Experiments in vitro using human liver microsomes showed that rabeprazole inhibits the metabolism of cyclosporine with IC₅₀ 62 μmol, i.e. in a concentration 50 times greater than Сmах for healthy volunteers after 20 days of taking 20 mg of rabeprazole. The degree of inhibition is similar to that of omeprazole for equivalent concentrations.

Slows the excretion of certain drugs metabolized in the liver by microsomal oxidation (diazepam, phenytoin, indirect anticoagulants).

The concentrations of rabeprazole and the active metabolite of clarithromycin, when used simultaneously, are increased by 24% and 50%, respectively. This increases the effectiveness of this combination during eradication of H. pylori.

Special instructions:

Precautionary measures

According to the indications, which require taking the drug once a day, Beret's drug should be taken in the morning before meals. It has been established that neither the time of day nor the intake of food affects the activity of rabeprazole, but the recommended time of taking the tablets contributes to better adherence to the baking scheme by the patients.

For the eradication of H. pylori in the appointment of rabeprazole in combination with two suitable antibiotics, the drug should be taken 2 times a day. In patients who are hypersensitive to antibiotics, allergic reactions are possible, from relatively light antibiotic-associated diarrhea to pseudomembranous colitis.

Before the beginning of therapy with the drug, it is necessary to exclude the presence of malignant neoplasm of the stomach, since taking the drug can mask the symptoms and delay the correct diagnosis.

In some patients with exacerbation of peptic ulcer of the duodenum, a good effect is obtained by taking one tablet of Beret's drug 10 mg once a day.

In most patients, duodenal ulcers heal within four weeks, but some patients may need an additional 4-week course of Beret's treatment to heal ulcers.

Most patients with gastric ulcer have healing within six weeks, but some patients may need an additional 6-week course of Beret's treatment to heal ulcers.

It is advisable to use caution when first prescribing the drug to patients with severe impairment of liver function. Patients with impaired renal or moderate liver function are not required to adjust the dose. The drug is not recommended for children under 12 years of age, since there is currently no experience of its use in patients of this age group.

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

The peculiarity of pharmacodynamics of rabeprazole and the profile ofpenniesx effects make it unlikely that it will influence the ability to drive vehicles and control mechanisms.However, if drowsiness occurs, dizziness should be avoided.

Form release / dosage:

Tablets, covered with enteric coating, 10 mg and 20 mg.

Packaging:By 7, 10, 14 tablets in a contour mesh box made of polymer film and aluminum foil. 1 circuit cell pack of 14 tablets or 2 contour packs of 7 tablets or 10 tablets together with the instructions for use are placed in a pack of cardboard. For 14 or 20 tablets in a vial of polymer with the control of the first dissection, with an insert of silica gel. Each bottle along with the instruction is placed in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001953

Date of registration:25.12.2012

The owner of the registration certificate:VEROPHARM SA VEROPHARM SA Russia

Manufacturer: & nbsp

VEROPHARM SA Russia

Information update date: & nbsp11.12.2013

Illustrated instructions

Instructions

Bereta® (Bereta®)