Rabeprazole original drug name. Rabeprazole-s tablets: instructions for use

Rabeprazole is an anti-ulcer, anti-stress, proton pump-inhibiting drug. Instructions for use indicate that capsules or tablets of 10 mg and 20 mg help with stomach and duodenal ulcers, gastritis, reflux in adults and children.

Composition and form of release

Rabeprazole is enteric capsules, the number of which in one package can vary from 5 to 60 pieces.

1 capsule contains active substance: rabeprazole sodium - 10/20 mg. Instructions for use with a description of its properties are enclosed in the box with the preparation.

What helps Rabeprazole?

Indications for the use of the drug include:

• peptic ulcer of the stomach and duodenum associated with Helicobacter pylori (helicobacter) (in combination with antibiotics);
• gastritis;
• peptic ulcer of the stomach and duodenum in the acute phase;
• gastroesophageal reflux.

Important! Only a doctor should decide on the need for course pharmacotherapy. Self-medication is absolutely unacceptable.

Instructions for use

Rabeprazole is taken orally, regardless of food intake and time of day. The capsules must be swallowed whole.

The dosage regimen is determined by the indications:

• erosive and ulcerative GERD or reflux esophagitis: 10 or 20 mg once a day. Cure usually occurs after 4-8 weeks of therapy, but sometimes the drug is continued for another 8 weeks;
• eradication of Helicobacter pylori in patients with peptic ulcer: 20 mg 2 times a day (Rabeprazole-SZ is used according to a certain scheme with an appropriate combination of antibiotics) for 7 days;
• exacerbation peptic ulcer duodenum: 20 mg 1 time per day, some patients to achieve therapeutic effect it is enough to take Rabeprazole at a dose of 10 mg. Therapy is carried out in a course of 2-4 weeks, according to the indications, the drug can be extended for another 4 weeks;
• exacerbation of gastric ulcer and anastomotic ulcer: 10 or 20 mg 1 time per day. The cure usually occurs after 6 weeks of therapy, but sometimes the drug is continued for another 6 weeks;
• Zollinger-Ellison syndrome and other conditions that are characterized by pathological hypersecretion: the dose is selected individually. At the beginning of therapy, the use of Rabeprazole in a daily dose of 60 mg is indicated, then it is increased to 100 mg (in one dose) or 120 mg (in two equal doses); for some patients, fractional dosing is more preferable. The duration of therapy is determined by clinical need, in some cases it was carried out for 12 months;
• GERD (maintenance): 10 or 20 mg 1 time per day. The duration of treatment is determined by the indications;
• NERD without esophagitis: 10 or 20 mg once daily. Usually the symptoms disappear after 4 weeks of therapy, if this does not happen, the patient is assigned an additional study. After relief of symptoms in order to prevent their subsequent development, Rabeprazole can be used on demand 10 mg once a day.

In patients with mild to moderate hepatic insufficiency, the concentration of rabeprazole in the blood, in comparison with healthy volunteers, is usually higher. When prescribing Rabeprazole against the background of severe hepatic insufficiency, care must be taken.

For children over 12 years of age in the treatment of GERD, the safety profile has been studied for a daily dose of 20 mg (in one dose) for up to 8 weeks.

Pharmacological effects

Antiulcer agent, inhibitor of HK-ATPase (proton pump). The mechanism of action is associated with the inhibition of the enzyme H-K-ATPase in the parietal cells of the stomach, which leads to blocking the final stage of the formation of hydrochloric acid. This action is dose-dependent and leads to inhibition of both basal and stimulated hydrochloric acid secretion, regardless of the nature of the stimulus.

Contraindications

Absolute:

• sucrase / isomaltase deficiency, fructose intolerance, glucose-galactose deficiency;
• pregnancy and period breastfeeding;
• age up to 12 (in the treatment of GERD) or 18 years (for other indications);
• individual intolerance to the components of the drug, as well as substituted benzimidazoles.

Relative (Rabeprazole-SZ capsules are prescribed under medical supervision):

• severe renal failure;
• severe liver failure.

Side effects

When using the drug from the gastrointestinal tract, respiratory and nervous system, as well as the musculoskeletal system, the following side effects may occur:

• allergic reaction in the form of a rash;
• diarrhea, loss of appetite, stomatitis, vomiting and nausea, constipation, dryness of the oral mucosa, increased activity of hepatic transaminases, flatulence;
• back pain;
• convulsions, myalgia, arthralgia;
• sinusitis, pharyngitis, cough and rhinitis;
• fever;
• dizziness, asthenia, drowsiness, impaired vision and taste receptors, headache,
• leukopenia, and thrombocytopenia.

drug interaction

With simultaneous use with digoxin, an increase (from small to moderate) in the concentration of digoxin in the blood plasma is possible. With simultaneous use with ketoconazole, its bioavailability decreases.

Patients receiving ketoconazole or rabeprazole at the same time need additional monitoring (dose adjustment of these drugs may be required). Plasma concentrations of rabeprazole and the active metabolite of clarithromycin, when taken simultaneously, increase by 24% and 50%, respectively.

This increases the effectiveness of this combination in the eradication of Helicobacter pylori. The study found no interaction of rabeprazole with liquid antacids. There was no clinically significant interaction of rabeprazole with food.

Special conditions

When using the drug for at least 3 months, in rare cases, the development of asymptomatic or symptomatic hypomagnesemia was noted. Most often, these violations were reported one year after taking Rabeprazole. Serious adverse reactions were tetany, convulsions and arrhythmia. Most patients required therapy for hypomagnesemia. This included magnesium replacement and withdrawal of inhibitors. proton pump.

In patients receiving long-term treatment or taking the drug in combination with digoxin, or medicines, which can lead to the development of hypomagnesemia (in particular, with diuretics), it is necessary to control the magnesium content before starting the medication and during therapy. During treatment, the risk of fractures of the hip, spine or wrist associated with osteoporosis may increase.

The risk is higher in patients who take high doses of rabeprazole for a long time (12 months or longer). According to literature sources, with the combined use of Rabeprazole with methotrexate (mainly in high doses), it is possible to increase the concentration of methotrexate and / or hydroxymethotrexate (its metabolite) and increase T1 / 2, which can lead to methotrexate toxicity.

If it is necessary to use high doses of methotrexate, the possibility of temporary withdrawal of Rabeprazole should be considered. Taking this medicine may increase the risk of gastrointestinal infections, including those caused by Salmonella, Clostridium difficile, and Campylobacter.

Influence on the ability to drive vehicles and complex mechanisms When driving vehicles and working with complex mechanisms, patients should take into account the likelihood of drowsiness.

Rabeprazole's analogs

Analogues are prescribed for treatment:

• Hairabezol;
• Vero-rabeprazole;
• Zolispan;
• Rabeprazole-OBL;
• Noflux;
• Zulbeks;
• Rabelok;
• Ontime.

It should be noted that the price of Rabeprazole analogues is on average twice the cost of this drug.

Differences between Rabeprazole and Omeprazole

Although the two drugs are similar in their chemical composition and are used in the treatment of similar diseases, according to experts in some cases, for example, with gastroesophageal reflux disease, a drug such as Rabeprazole fights symptoms more effectively, and also accelerates the process of restoring the normal functioning of the esophagus.

Terms of dispensing from pharmacies

Released by prescription.

Price

The average price of Rabeprazole, enteric capsules 10 mg, 28 pieces (Moscow), is 180 rubles.

Store Rabeprazole instructions for use in a place protected from light, at temperatures up to 25 ° C. Keep away from children. Shelf life - 3 years.

- Peptic ulcer of the stomach in the acute phase and ulcer of the anastomosis;

- peptic ulcer of the duodenum in the acute stage;

- erosive and ulcerative gastroesophageal reflux disease in adults and children over 12 years of age or reflux esophagitis;

- maintenance therapy of gastroesophageal reflux disease;

- nonerosive gastroesophageal reflux disease;

- Zollinger-Ellison syndrome and other conditions characterized by pathological hypersecretion;

- in combination with appropriate antibiotic therapy for eradicationHelicobacter pyloriin patients with gastric ulcer.

- Hypersensitivity to rabeprazole, substituted benzimidazoles or to auxiliary components of the drug;

- pregnancy;

- breastfeeding period;

- children under 18 years of age, with the exception of use in gastroesophageal reflux disease - children under 12 years of age;

- lactase deficiency;

- lactose intolerance;

- glucose-galactose malabsorption.

Symptoms

Data on intentional or accidental overdose are minimal. There were no cases of severe overdose with rabeprazole.

Treatment

The specific antidote for the drug is unknown. binds well to plasma proteins, and therefore is poorly excreted during dialysis. In case of overdose, symptomatic and supportive treatment should be carried out.

2 years.

Do not use after the expiration date.

A drug Rabeprazole- an agent for the treatment of peptic ulcers and gastroesophageal reflux disease, an inhibitor of the "proton pump".

Antisecretory, antiulcer agent - inhibitor of H +, K + - ATPase (“proton pump”). Accumulating and passing into active form in the acidic environment of the secretory tubules of the parietal cells of the gastric mucosa. The active metabolite - sulfenamide - inhibits (partially reversible) H +, K + - ATPase, stopping the release of hydrogen ions into the stomach cavity, which leads to blocking of the final stage of hydrochloric acid secretion. Dose-dependently inhibits both basal and stimulated secretion, the total volume of gastric secretion and the release of pepsin. It has a bactericidal effect against Helicobacter pylori (the minimum inhibitory concentration is 4-16 μg / ml), accelerates the manifestation of anti-Helicobacter pylori activity of a number of antibiotics.

After a single dose of 20 mg of rabeprazole, inhibition of gastric secretion develops within 1 hour and reaches a maximum after 2-4 hours (after taking the first dose). The duration of inhibition of basal and stimulated secretion reaches 48 hours, a stable antisecretory effect develops after 3 days of treatment. The ability of parietal cells to produce hydrochloric acid is restored within 2-3 days after the end of therapy as new molecules of H +, K + - ATPase are synthesized, cancellation is not accompanied by the “rebound” phenomenon. Rabeprazole in combination with antibiotics provides eradication of Helicobacter pylori in 90% of patients within 4 days.

Pharmacokinetics.

After ingestion, absorption begins at small intestine(due to the presence of an acid-resistant enteric coating in the tablet) and is carried out quickly and completely. Bioavailability is 52% due to the pronounced effect of the "first pass" through the liver; Simultaneous ingestion of food does not affect bioavailability. Plasma protein binding is 95%. In the dose range of 10-40 mg, the bioavailability and maximum concentration of rabeprazole depend linearly on the dose. After taking 20 mg of rabeprazole, the maximum plasma concentration is reached, on average, after 3.5 hours. It is metabolized in the liver with the participation of isoenzymes of the cytochrome P450 system (CYP2C19 and CYP3A) with the formation of inactive metabolites and demethylthioether, which has a weak antisecretory activity. The half-life is 0.7-1.5 hours, the total clearance is 283 ml / min. It is excreted mainly by the kidneys in the form of metabolites - conjugates of mercapturic and carboxylic acids.

In liver diseases, the bioavailability of rabeprazole increases by 2 times (after a single dose) and 1.5 times (after 7 days of therapy), the half-life increases to 12.3 hours.

In the case of delayed biotransformation, after 7 days of taking a daily dose of 20 mg, the maximum concentration increases by 40%, the half-life is, on average, 1.6 hours.

At the stage of terminal renal failure in patients on dialysis, pharmacokinetic parameters change slightly: the maximum concentration and bioavailability decrease by 35%, the half-life during hemodialysis is 0.95 hours, after 3.6 hours.

In elderly patients, the maximum concentration in the blood increases by 60%, bioavailability increases by 2 times, elimination slows down.

Indications for use

• active peptic ulcer of the duodenum;
• active benign gastric ulcer;
• erosive or ulcerative gastroesophageal reflux disease (GERD);
• long-term treatment of gastroesophageal reflux disease (maintenance therapy for GERD);
• symptomatic treatment of moderate to very severe gastroesophageal reflux disease (symptomatic treatment of GERD);
• Zollinger-Ellison syndrome;
• in combination with appropriate antibacterial therapeutic regimens for the eradication of Helicobacter pylori (H. pylori) in patients with peptic ulcers of the stomach and duodenum.

Mode of application

Adults and elderly patients.

Active peptic duodenal ulcer and active benign gastric ulcer: The recommended dose for these conditions is 20 mg once daily in the morning.

In most patients with an active peptic duodenal ulcer, the time required for the ulcer to heal is up to 4 weeks.

However, it should be noted that some patients need to take Rabeprazole-Health additionally for another 4 weeks. Most patients with active benign gastric ulcers heal within 6 weeks, but some patients who are unresponsive to treatment may need to take Rabeprazole-Health for an additional 6 weeks to heal their ulcers.

Erosive or ulcerative gastroesophageal reflux disease: The recommended dose for these diseases is 20 mg 1 time per day for 4-8 weeks.

Long-term treatment of gastroesophageal reflux disease (maintenance therapy for GERD):

for long-term use, maintenance doses of Rabeprazole-Health 10 mg or 20 mg 1 time per day can be used (dose-dependent on the effectiveness of treatment).

Symptomatic treatment of GERD: for patients without esophagitis, Rabeprazole-Health is prescribed at a dose of 10 mg 1 time per day. If after 4 weeks of treatment the symptoms do not disappear, an additional examination of the patient should be carried out. Once symptoms have resolved, subsequent symptom control can be achieved using an on-demand regimen of 10 mg once daily as needed.

Zollinger-Ellison syndrome: the dose is selected individually. The initial dose is 60 mg per day. A single dose of up to 100 mg per day can be used. If necessary, the dose is increased and the drug is prescribed at a dose of up to 120 mg per day with a single dose or 60 mg 2 times a day. Treatment is continued when clinically necessary. The duration of the course of treatment and the dosage regimen is determined individually.

H. pylori eradication: In patients with H. pylori, appropriate combinations of Rabeprazole-Health with antibiotics should be used. Recommended appointment within 7 days:

Rabeprazole-Health 20 mg 2 times a day + clarithromycin 500 mg 2 times a day and amoxicillin 1 g 2 times a day.

For indications that require taking only once a day, Rabeprazole-Health tablets should be taken in the morning before meals. Although the morning or meal did not show an effect on rabeprazole sodium, this regimen is more favorable for treatment. Tablets should not be chewed or crushed, but should be swallowed whole.

Impaired kidney and liver function. Patients with impaired renal or hepatic function do not require dose adjustment. Rabeprazole-Health. The use in the treatment of patients with severely impaired liver function is discussed in more detail in the section "Peculiarities of use".

Side effects

In clinical trials Rabeprazole-Health well tolerated by patients. The side effects that were observed were for the most part minor, moderate and quickly passed. The most common negative manifestations are headache, diarrhea and nausea. Adverse reactions that were observed more often are listed below by organ system and frequency.

The following adverse reactions have been observed during clinical research. However, from these adverse reactions that were observed during clinical studies, only headache, diarrhea, abdominal pain, asthenia, flatulence, rash and dry mouth were associated with the use of Rabeprazole-Health.

Infections and invasions. Often - infections.

Blood and lymphatic system. Rarely - neutropenia, leukopenia, thrombocytopenia, leukocytosis.

From the immune system. Rarely - hypersensitivity reactions (including swelling of the face, arterial hypotension and dyspnea; erythema, bullous reactions and acute systemic allergic reactions, which usually disappear after stopping treatment).

From the side of metabolism. Rarely - anorexia. Not known - hyponatremia.

Mental disorders. Often insomnia. Infrequently - nervousness. Rarely - depression. Unknown - confusion.

From the side of the nervous system. Often - headache, dizziness. Infrequently - drowsiness.

From the side of the organ of vision. Rarely - visual disturbances.

vascular disorders. Not known - peripheral edema.

From the respiratory system. Often - cough, pharyngitis, rhinitis. Infrequently - bronchitis, sinusitis.

From the digestive tract. Often - diarrhea, vomiting, nausea, abdominal pain, constipation, flatulence. Infrequently - dyspepsia, dry mouth, belching. Rarely - gastritis, stomatitis, a violation of the sense of taste.

Disorders of the liver and biliary tract. Rarely - hepatitis, jaundice, hepatic encephalopathy (in single cases, hepatic encephalopathy was observed in patients with cirrhosis).

From the skin and subcutaneous tissues. Infrequently - rash, erythema (bullous reactions and acute systemic allergic reactions, which usually disappear after stopping treatment). Rarely - itching, sweating, bullous reactions. Very rarely - erythema multiforme, toxic epidermal necrosis (TEN), Stevens-Johnson syndrome.

From the musculoskeletal system. Often - non-specific pain / back pain. Infrequently - myalgia, leg cramps, arthralgia.

From the side of the kidneys and urinary system. Infrequently - urinary tract infections. Rarely - interstitial nephritis.

From the side reproductive system. Not known - gynecomastia.

General disorders and applications. Often - asthenia, flu-like syndrome. Infrequently - chest pain, chills, fever.

Research. Infrequently - an increase in the level of liver enzymes. Rarely - weight gain.

Contraindications

Contraindications to the use of the drug Rabeprazole are: the presence of a malignant process in the stomach and duodenum, pregnancy, lactation period, individual hypersensitivity to rabeprazole, other components of the drug, substituted benzimidazoles.

Pregnancy

Safety studies of the use of rabeprazole in pregnant women have not been conducted, therefore, the use Rabeprazole-Health contraindicated in pregnancy. It is not known whether rabeprazole sodium is excreted in human milk. Relevant studies have not been conducted, so Rabeprazole-Health should not be given to women during lactation.

Interaction with other drugs

Rabeprazole sodium causes a strong and prolonged decrease in gastric acid production. Thus, sodium rabeprazole, in principle, can interact with drugs, the absorption of which depends on the pH of the gastric contents. The simultaneous use of rabeprazole sodium and ketoconazole or itraconazole can lead to a significant decrease in plasma levels of these antifungals.

Thus, individual patients who use these drugs together with Rabeprazole-Health, should be monitored to determine the need for dose adjustment. In clinical trials, patients simultaneously with Rabeprazole-Health took antacids as needed; in a special study, no interaction was observed between Rabeprazole-Zdorovye and an antacid taken as a liquid.

Co-administration of atazanavir 300 mg/ritonavir 100 mg with omeprazole (40 mg once daily) or atazanavir 400 mg with lansoprazole (60 mg once daily) in healthy volunteers resulted in a significant reduction in atazanavir exposure. The absorption of atazanavir is pH dependent, so proton pump inhibitors, including rabeprazole, should not be used in combination with atazanavir.

Overdose

Experience with intentional or accidental overdose Rabeprazole limited. The maximum reported exposure did not exceed 60 mg twice daily or 160 mg once daily. In general, the impact is minimal, characteristic of known adverse reactions and reversible without subsequent medical effects. The specific antidote for Rabeprazole-Health is unknown. Sodium rabeprazole binds well to plasma proteins and is not excreted during dialysis. In case of overdose, symptomatic and supportive treatment should be carried out.

Storage conditions

Additionally

Symptomatic improvement in response to rabeprazole therapy may also occur in the presence of malignant neoplasm stomach, and therefore, before starting therapy with Rabeprazole-Health, it is necessary to exclude the possibility of the presence of tumors. Patients with a long course of treatment (especially those treated for more than one year) should be regularly examined.

The risk of cross-hypersensitivity with other proton pump inhibitors or substituted benzimidazoles cannot be ruled out.

Patients should be warned that Rabeprazole-Health tablets should not be chewed or crushed, but should be swallowed whole.

There have been post-marketing reports of pathological changes blood (thrombocytopenia and neutropenia). In most cases, no other etiology was found; cases were uncomplicated and disappeared after discontinuation of rabeprazole.

Abnormal liver enzymes have been observed in clinical studies and there have also been post-marketing reports. In most cases, no other etiology was found; cases were uncomplicated and disappeared after discontinuation of rabeprazole.

In a special study in patients with mild or moderate hepatic impairment, there was no significant abolition of the frequency of side effects when taking Rabeprazole-Health compared with the control group of the corresponding sex and age.

The physician should exercise caution when prescribing early stages therapy of the drug in patients with severely impaired renal function, since there are no clinical data on the use of the drug in patients of this group.

The simultaneous use of atazanavir and Rabeprazole-Zdorovye is not recommended (see section "Interaction with other medicinal products and other types of interactions").

Given the pharmacodynamics of rabeprazole sodium and its inherent side effect profile, it can be assumed that Rabeprazole-Health should not adversely affect driving and working with potentially dangerous mechanisms. However, in case of drowsiness, it is recommended to avoid driving and operating other mechanisms.

main parameters

A drug:

International name: Rabeprazole
Dosage form: enteric-coated tablets

Pharmachologic effect:
An antiulcer agent from the group of proton pump inhibitors (H + / K + -ATPase), is metabolized in the parietal cells of the stomach to active sulfonamide derivatives, which inactivate the sulfhydryl groups of H + / K + -ATPase. Blocks the final stage of HCl secretion, reducing the content of basal and stimulated secretion, regardless of the nature of the stimulus. It has a high lipophilicity, easily penetrates into the parietal cells of the stomach and concentrates in them, providing a cytoprotective effect and increasing the secretion of bicarbonate. The antisecretory effect after oral administration of 20 mg occurs within 1 hour and reaches a maximum after 2-4 hours; inhibition of basal and food-stimulated acid secretion 23 hours after taking the first dose is 62 and 82%, respectively, the duration of action is 48 hours. After the end of the intake, secretory activity returns to normal within 2-3 days. In the first 2-8 weeks of therapy, the concentration of gastrin in the blood serum increases and returns to baseline within 1-2 weeks after withdrawal. Does not affect the central nervous system, cardiovascular and respiratory systems.

Pharmacokinetics:
Absorption is high, TCmax is 3.5 hours. Cmax and AUC are linear in the dose range from 10 to 40 mg. Metabolized in the liver with the participation of cytochrome isoenzymes CYP2C9 and CYP3A. Bioavailability - 52%, does not increase with repeated administration. T1 / 2 - 0.7-1.5 h, clearance - 283 ± 98 ml / min. In patients with hepatic insufficiency, AUC increases by 2 times, T1 / 2 - by 2-3 times. In elderly patients, AUC increases by 2 times, Cmax - by 60%. Communication with plasma proteins - 97%. Excreted by the kidneys - 90% in the form of 2 metabolites: a conjugate of mercapturic acid (M5) and carboxylic acid (M6); through the intestines - 10%.

Indications:
Peptic ulcer of the stomach and duodenum (treatment), gastroesophageal reflux disease, Zollinger-Ellison syndrome, stress ulcers of the gastrointestinal tract. As part of complex therapy: eradication of Helicobacter pylori in patients with gastric ulcer and 12 duodenal ulcer or chronic gastritis; treatment and prevention of recurrence of peptic ulcer associated with Helicobacter pylori.

Contraindications:
Hypersensitivity, pregnancy, lactation. With caution. Childhood, severe renal failure.

Dosing regimen:
Inside, 20 mg 1 time per day, in the morning. The course of treatment for gastric ulcer and duodenal ulcer - 4-6 weeks, if necessary - up to 12 weeks; with reflux esophagitis - 4-8 weeks. The tablets are swallowed whole, without chewing or crushing.

Side effects:
Nausea, constipation or diarrhea, abdominal pain, flatulence, headache, dizziness, drowsiness, weakness, skin rash, increased activity of "liver" transaminases, thrombocytopenia, leukopenia; pharyngitis, rhinitis, asthenia, back pain, flu-like syndrome, myalgia, dryness of the oral mucosa, calf muscle cramps, arthralgia, fever. Rarely - loss of appetite, weight gain, depression, impaired vision or taste, stomatitis, increased sweating.

Special instructions:
Before and after treatment, endoscopic control is required to exclude a malignant neoplasm, because. treatment can mask symptoms and delay correct diagnosis. The drug does not affect the function thyroid gland, carbohydrate metabolism, blood levels of parathyroid hormone, cortisol, estrogen, testosterone, prolactin, cholecystokinin, secretin, glucagon, FSH, LH, renin, aldosterone and growth hormone.

Interaction:
Slows down the excretion of some drugs metabolized in the liver by microsomal oxidation (diazepam, phenytoin, indirect anticoagulants). Reduces the concentration of ketoconazole by 33%, digoxin - by 22%.

Catad_pgroup Antisecretory, proton pump inhibitors

Rabeprazole 20mg - instructions for use

Registration number:

Trade name:

Rabeprazole

International non-proprietary name:

rabeprazole

Dosage form:

enteric coated tablets

Compound

1 enteric coated tablet 20 mg contains:
The composition of the tablet core:
Active substance: rabeprazole sodium - 20.0 mg, corresponds to rabeprazole - 18.85 mg.
Excipients: magnesium oxide, low-substituted hyprolose (hydroxypropylcellulose), mannitol, hypromellose, sodium stearyl fumarate.
The composition of the tablet shell 1: Opadray colorless 03K19229 (hypromellose, triacetin, talc), magnesium oxide.
The composition of the tablet shell 2: Shureliz colorless E-7-19040 (ethylcellulose, ammonium hydroxide, medium chain triglycerides, oleic acid).
The composition of the tablet shell 3: acrylyse II yellow 493Z220000 (methacrylic acid and ethyl acrylate copolymer (1:1), talc, titanium dioxide, poloxamer 407, calcium silicate, sodium bicarbonate, sodium lauryl sulfate, iron oxide yellow).

Description

Tablets 20 mg: tablets are round, biconvex, film-coated from light yellow to yellow.

Pharmacotherapeutic group:

a means that reduces the secretion of the glands of the stomach - a proton pump inhibitor.

ATC Code:

Pharmacological properties

Pharmacodynamics
Mechanism of action
Rabeprazole sodium belongs to the class of antisecretory substances derived from benzimidazole. Rabeprazole sodium inhibits the secretion of gastric juice by specific inhibition of H + /K + ATPase on the secretory surface of the parietal cells of the stomach. H + /K + ATPase is a protein complex that functions as a proton pump, thus rabeprazole sodium is an inhibitor of the proton pump in the stomach and blocks the final stage of acid production. This effect is dose-dependent and leads to the suppression of both basal and stimulated acid secretion, regardless of the stimulus. Rabeprazole sodium does not have anticholinergic properties.
Antisecretory action
After oral administration of 20 mg of rabeprazole sodium, the antisecretory effect develops within an hour. Inhibition of basal and stimulated acid secretion 23 hours after the first dose of rabeprazole sodium is 69% and 82%, respectively, and lasts up to 48 hours. This duration of pharmacodynamic action is much longer than predicted based on the half-life (approximately one hour). This effect can be explained by the prolonged binding of the drug to the H + /K + ATPase of the 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. When you stop taking it, secretory activity is restored within 1-2 days.
Effect on plasma gastrin levels
In clinical studies, patients received 10 or 20 mg of rabeprazole sodium daily for up to 43 months of treatment. Plasma gastrin levels were elevated during the first 2-8 weeks, reflecting an inhibitory effect on acid secretion. The concentration of gastrin returned to baseline usually within 1-2 weeks after cessation of treatment.
Effect on enterochromaffin-like cells
In the study of human gastric biopsy specimens from the antrum and gastric fundus of 500 patients treated with rabeprazole sodium or a comparator for 8 weeks, persistent changes in the morphological structure of enterochromaffin-like cells, the severity of gastritis, the frequency of atrophic gastritis, intestinal metaplasia, or the spread of infection Helicobacter pylori were not found.
In a study involving more than 400 patients treated with rabeprazole sodium (10 mg/day or 20 mg/day) for 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 has been reported.
Other effects
Systemic effects of rabeprazole sodium on the central nervous system, cardiovascular or respiratory systems have not been found at the moment. It has been shown that rabeprazole sodium, when taken orally at a dose of 20 mg for 2 weeks, has no effect on thyroid function, carbohydrate metabolism, blood parathyroid hormone levels, as well as cortisol, estrogens, testosterone, prolactin, glucagon, follicle-stimulating hormone. (FSH), luteinizing hormone (LH), renin, aldosterone and growth hormone.

Pharmacokinetics
Absorption
Rabeprazole is rapidly absorbed from the intestine and peak plasma concentrations are reached approximately 3.5 hours after a 20 mg dose. Changes in peak plasma concentrations (Cmax) and area under the concentration-time curve (AUC) of rabeprazole are linear in the dose range from 10 to 40 mg. Absolute bioavailability after oral administration of 20 mg (compared with intravenous administration) is about 52%. In addition, bioavailability does not change with repeated administration of rabeprazole. In healthy volunteers, the plasma half-life is about 1 hour (ranging from 0.7 to 1.5 hours), and the total clearance is 3.8 ml / min / kg. In patients with chronic liver disease, AUC is doubled compared with healthy volunteers, indicating a decrease in first-pass metabolism, and the plasma half-life is increased 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 down the absorption of rabeprazole by 4 hours or more, but neither Cmax nor the degree of absorption change.
Distribution
In humans, the degree of binding of rabeprazole to plasma proteins is about 97%.
Metabolism and excretion
At healthy people
After a single oral dose of 20 mg of 14 C-labeled rabeprazole sodium, no unchanged drug was found in the urine. About 90% of rabeprazole is excreted in the urine mainly in the form of two metabolites: a conjugate of mercapturic acid (M5) and carboxylic acid (M6), as well as in the form of two unknown metabolites identified during toxicological analysis. The remainder of the ingested rabeprazole sodium is excreted in the feces.
The total excretion is 99.8%. These data indicate a small excretion of metabolites of rabeprazole sodium in the bile. The main metabolite is thioether (M1). The only active metabolite is desmethyl (M3), however, it was observed in low concentrations in only one study participant after taking 80 mg of rabeprazole.
End stage renal disease
In patients with stable end-stage renal disease requiring maintenance hemodialysis (creatinine clearance<5 мл/мин/1,73 м²), выведение рабепразола натрия схоже с таковым для здоровых добровольцев. AUC и С max у этих пациентов было примерно на 35% ниже, чем у здоровых добровольцев. В среднем период полувыведения рабепразола составлял 0,82 ч у здоровых добровольцев, 0,95 ч у пациентов во время гемодиализа и 3,6 ч после гемодиализа. Клиренс препарата у пациентов с заболеваниями почек, нуждающихся в гемодиализе, был приблизительно в два раза выше, чем у здоровых добровольцев.
Chronic compensated cirrhosis
Patients with chronic compensated liver cirrhosis tolerate rabeprazole sodium at a dose of 20 mg 1 time per day, although AUC is doubled and C max is increased by 50% compared with healthy volunteers of the corresponding sex.
Elderly patients
In elderly patients, the elimination of rabeprazole is somewhat slower. After 7 days of taking rabeprazole 20 mg per day in elderly people, AUC was approximately twice as high, and C max was increased by 60% compared with young healthy volunteers. However, there were no signs of accumulation of rabeprazole.
CYP2C19 polymorphism
In patients with a slow metabolism of CYP2C19, after 7 days of taking rabeprazole at home 20 mg per day, the AUC increases by 1.9 times, and the elimination half-life by 1.6 times compared with the same parameters in "rapid metabolizers", while at the same time as With max increases by 40%.

Indications for use

• Peptic ulcer of the stomach in the acute stage and ulcer of the anastomosis;
• Peptic ulcer of the duodenum in the acute stage;
• Erosive and ulcerative gastroesophageal reflux disease or reflux esophagitis;
• Maintenance therapy of gastroesophageal reflux disease;
• Nonerosive gastroesophageal reflux disease;
• Zollinger-Ellison syndrome and other conditions characterized by pathological hypersecretion;
• In combination with appropriate antibiotic therapy for eradication Helicobacter pylori in patients with peptic ulcer.

Contraindications

• Hypersensitivity to rabeprazole, substituted benzimidazoles or to any of the excipients of the drug;
• Pregnancy;
• The period of breastfeeding;
• Age up to 12 years.

Carefully

• Childhood;
• Severe renal failure.

Use during pregnancy and during breastfeeding

There are no data on the safety of rabeprazole during pregnancy. Reproductive studies in rats and rabbits have not revealed signs of impaired fertility or fetal developmental defects caused by rabeprazole; however, in rats, the drug crosses the placental barrier in small amounts. Rabeprazole should not be used during pregnancy unless the expected benefit to the mother outweighs the potential harm to the fetus.
It is not known whether rabeprazole is excreted in breast milk. Appropriate studies have not been conducted in lactating women. However, rabeprazole is found in the milk of lactating rats, and therefore rabeprazole should not be administered to lactating women.

Dosage and administration

Rabeprazole tablets should not be chewed or crushed. Tablets should be swallowed whole. It has been established that neither time of day nor food intake affect the activity of rabeprazole sodium.
With peptic ulcer of the stomach in the acute stage and ulcer of the anastomosis It is recommended to take 20 mg orally once a day. Usually the cure occurs after 6 weeks of therapy, however, in some cases, the duration of treatment can be increased by another 6 weeks.
With peptic ulcer of the duodenum in the acute stage It is recommended to take 20 mg orally once a day. The duration of treatment is from 2 to 4 weeks. If necessary, the duration of treatment can be increased by another 4 weeks.
In the treatment of erosive gastroesophageal reflux disease or reflux esophagitis It is recommended to take 20 mg orally once a day. The duration of treatment is from 4 to 8 weeks. If necessary, the duration of treatment can be increased by another 8 weeks.
For maintenance therapy of gastroesophageal reflux disease It is recommended to take 20 mg orally once a day. The duration of treatment depends on the condition of the patient.
For non-erosive gastroesophageal reflux disease without esophagitis It is recommended to take 20 mg orally once a day. If after four weeks of treatment the symptoms do not disappear, an additional study of the patient should be carried out. After relief of symptoms, to prevent their subsequent occurrence, the drug should be taken orally 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 is prescribed at a dose of up to 100 mg per day with a single dose or 60 mg twice a day. For some patients, fractional dosing of the drug is preferable. Treatment should be continued as clinically necessary. In some patients with Zollinger-Ellison syndrome, the duration of treatment with rabeprazole was up to one year.
For the eradication of Helicobacter pylori it is recommended to take orally 20 mg 2 times a day according to a certain scheme with an appropriate combination of antibiotics. The duration of treatment is 7 days.
Patients with renal and hepatic insufficiency
Dose adjustment in patients with renal insufficiency is not required.
In patients with mild to moderate hepatic insufficiency, the concentration of rabeprazole in the blood is usually higher than in healthy patients.
Caution should be exercised when prescribing rabeprazole to patients with severe hepatic impairment.
Elderly patients
Dose adjustment is not required.
Children
The safety and efficacy of rabeprazole sodium 20 mg for the short-term (up to 8 weeks) treatment of gastroesophageal reflux disease in children aged 12 years and older is supported by extrapolation from adequate and well-controlled studies supporting the efficacy of rabeprazole sodium in adults and safety and pharmacokinetic studies in pediatric patients. age.
The recommended dose for children aged 12 years and over is 20 mg once daily for up to 8 weeks.
The safety and efficacy of rabeprazole sodium for the treatment of gastroesophageal reflux disease in children under 12 years of age have not been established. The safety and efficacy of rabeprazole sodium for other indications has not been established in pediatric patients.

Side effect

To determine the incidence of side effects of the drug, the following classification is used: very often (≥1 / 10); often (≥1/100 and<1/10); нечасто (≥1/1000 и <1/100); редко (≥1/10000 и <1/1000); очень редко (<1/10000), включая единичные случаи.
Immune system disorders: rarely - acute systemic allergic reactions.
Blood and lymphatic system disorders: rarely - thrombocytopenia, neutropenia, leukopenia.
Metabolic and nutritional disorders: rarely - hypomagnesemia.
Liver and biliary tract disorders: increased activity of liver enzymes, rarely - hepatitis, jaundice, hepatic encephalopathy;
Renal and urinary tract disorders: very rarely - interstitial nephritis.
Skin and subcutaneous tissue disorders: rarely - bullous rashes, urticaria; very rarely - erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome.
Musculoskeletal and connective tissue disorders: rarely - myalgia, arthralgia.
Genital and breast disorders: very rarely - gynecomastia. Changes in other laboratory parameters during the administration of rabeprazole sodium were not observed.
According to post-marketing observations, when taking proton pump inhibitors (PPIs), an increase in the risk of fractures is possible (see section "Special Instructions").

Overdose

Symptoms
Data on intentional or accidental overdose are minimal. There were no cases of severe overdose with rabeprazole.
Treatment
The specific antidote is unknown. Rabeprazole binds well to plasma proteins and therefore is poorly excreted during dialysis. In case of overdose, symptomatic and supportive treatment should be carried out.

Interaction with other drugs

Cytochrome P450 system
Rabeprazole sodium, like other PPIs, is metabolized via the cytochrome P450 (CYP450) system in the liver. In research in vitro on human liver microsomes, it was shown that rabeprazole sodium is metabolized by CYP2C19 and CYP3A4 isoenzymes. Studies in healthy volunteers have shown that rabeprazole sodium has no pharmacokinetic or clinically significant interactions with drugs that are metabolized by the cytochrome P450 system - warfarin, phenytoin, theophylline and diazepam (regardless of whether diazepam is heavily or weakly metabolized by patients).
A study of combination therapy with antibacterial drugs was conducted. This four-way crossover study included 16 healthy volunteers who received 20 mg rabeprazole, 1000 mg amoxicillin, 500 mg clarithromycin, or a combination of these drugs (RAC - rabeprazole, amoxicillin, clarithromycin). AUC and Cmax for clarithromycin and amoxicillin were similar when comparing combination therapy with monotherapy. The AUC and C max for rabeprazole increased by 11% and 34%, respectively, and for 14-hydroxyclarithromycin (the active metabolite of clarithromycin), AUC and C max increased by 42% and 46%, respectively, for combination therapy compared with monotherapy. This increase in exposure rates for rabeprazole and clarithromycin was not considered clinically significant.
Interaction due to inhibition of gastric acid secretion
Rabeprazole sodium provides sustained and prolonged suppression of gastric acid secretion. Thus, interaction with substances for which absorption depends on pH can occur. When taken simultaneously with rabeprazole sodium, the absorption of ketoconazole decreases by 30%, and the absorption of digoxin increases by 22%. Therefore, for some patients, monitoring should be carried out to decide whether dose adjustment is necessary while taking rabeprazole sodium with ketoconazole, digoxin or other drugs for which absorption is pH dependent.
Atazanavir
When atazanavir 300 mg/ritonavir 100 mg was co-administered with omeprazole (40 mg once daily) or atazanavir 400 mg with lansoprazole (60 mg once daily), a significant reduction in atazanavir exposure was observed in healthy volunteers. The absorption of atazanavir is pH dependent. Although co-administration with rabeprazole has not been studied, similar results are expected for other PPIs. Therefore, co-administration of atazanavir with PPIs, including rabeprazole, is not recommended.
Antacids
In clinical studies, antacids were used in conjunction with rabeprazole sodium. No clinically significant interactions of rabeprazole sodium with aluminum hydroxide gel or magnesium hydroxide were observed.
meal
In a clinical study, no clinically significant interactions were observed during the administration of rabeprazole sodium with a low-fat diet. Reception of rabeprazole sodium simultaneously with food enriched with fats can slow down the absorption of rabeprazole up to 4 hours or more, however, Cmax and AUC do not change.
Cyclosporine
Experiments in vitro using human liver microsomes showed that rabeprazole inhibits the metabolism of cyclosporine with an IC 50 of 62 µmol, i.e. at a concentration 50 times higher than Cmax 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.
Methotrexate
Adverse event reports, published pharmacokinetic studies, and retrospective analysis suggest that concomitant use of PPIs and methotrexate (primarily at high doses) may lead to an increase in the concentration of methotrexate and/or its metabolite hydroxymethotrexate and increase the half-life. However, there have been no specific drug interaction studies of methotrexate with PPIs.

special instructions

The patient's response to therapy with rabeprazole sodium does not exclude the presence of malignant neoplasms in the stomach.
Rabeprazole tablets should not be chewed or crushed. Tablets should be swallowed whole. It has been established that neither time of day nor food intake affect the activity of rabeprazole sodium.
In a special study in patients with mild or moderate hepatic impairment, no significant difference was found in the frequency of side effects of rabeprazole sodium from that in healthy individuals matched by sex and age, but despite this, caution is recommended when first prescribing rabeprazole sodium to patients with severe hepatic dysfunction. The AUC of rabeprazole sodium in patients with severe hepatic impairment is approximately two times higher than in healthy volunteers.
Patients with impaired renal or hepatic function do not need to adjust the dose of rabeprazole.
Hypomagnesemia
In the treatment of PPIs for at least 3 months, cases of symptomatic and asymptomatic hypomagnesemia have been observed in rare cases. In most cases, these reports were received a year after the therapy. Serious side effects were tetany, arrhythmia and convulsions. Most patients required treatment for hypomagnesaemia, including magnesium replacement and discontinuation of PPI therapy. In patients who will be on long-term treatment or who are taking PPIs with drugs such as digoxin or drugs that can cause hypomagnesaemia (eg, diuretics), healthcare professionals should monitor magnesium levels prior to initiating PPI treatment and during treatment.
Patients should not take other acid-reducing agents, such as H2-receptor blockers or PPIs, concomitantly with rabeprazole.
bone fractures
Observational studies suggest that PPI therapy may lead to an increased risk of osteoporosis-related fractures of the hip, wrist, or spine. The risk of fractures was increased in patients receiving high doses of PPIs for a long time (a year or more).
Simultaneous use of rabeprazole with methotrexate
According to the literature, the simultaneous use of PPIs with methotrexate (especially in high doses) can lead to an increase in the concentration of methotrexate and / or its metabolite hydroxymethotrexate and increase the half-life, which can lead to methotrexate toxicity. If high doses of methotrexate are required, temporary discontinuation of PPI therapy may be considered.
Clostridium difficile
PPI therapy may lead to an increased risk of gastrointestinal infections such as Clostridium difficile.

Influence on the ability to drive vehicles and mechanisms

Based on the pharmacodynamic characteristics of rabeprazole and its adverse effect profile, it is unlikely that it affects the ability to drive a car and operate machinery. However, if drowsiness occurs, these activities should be avoided.

Release form

Enteric-coated tablets, 20 mg.
7, 10 or 14 tablets in a blister pack made of PVC film and aluminum foil or 14, 28, 30 or 60 tablets in a low-pressure polyethylene jar, sealed with a low-pressure polyethylene lid with first opening control (insert on a polymer and cardboard base) or without it.
1, 2, 4 or 8 blisters of 7 tablets, or 1, 2 or 4 blisters of 14 tablets, or 1, 2, 3, 5, 6, 9 or 10 blisters of 10 tablets , or 1 jar together with instructions for medical use are placed in a pack of cardboard box.

Storage conditions

In a place protected from light at a temperature not exceeding 25 ° C.
Keep out of the reach of children.

Best before date

2 years.
Do not use after the expiration date.

Holiday conditions

On prescription.

Manufacturer

Izvarino Pharma LLC,

Consumer claims should be sent to:

142750, Moscow, Izvarino village, VNCMDL territory, building 1.