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

Active substanceRabeprazoleRabeprazole

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Dosage form: & nbspenteric coated tablets

Composition:

1 tablet dosage of 10 mg contains:

Active substance: Rabeprazole sodium in terms of 100% substance - 10 mg.

Excipients: calcium carbonate, lactose monohydrate, corn starch, hydroxypropylmethylcellulose (hypromellose), magnesium stearate.

Excipients of the separation layer: Opapray is white.

Excipients of enteric coating: acrylose pink, macrogol 6000 (polyethylene glycol).

1 tablet dosage of 20 mg contains:

Active substance: Rabeprazole sodium in terms of 100% of the substance - 20 mg.

Excipients: calcium carbonate, lactose monohydrate, corn starch, hydroxypropylmethylcellulose (hypromellose), magnesium stearate.

Excipients of the separation layer: Opapray is white.

Excipients of enteric coating: acrylitis yellow, macrogol 6000 (polyethylene glycol).

Description:

Tablets with a dosage of 10 mg

Round biconvex tablets are enteric, coated with a pink color. Roughness of the surface of tablets is allowed.

Tablets with a dosage of 20 mg

Round biconvex tablets are enteric, coated with a yellow color with a brownish tinge. Roughness of the surface of tablets is allowed.

Pharmacotherapeutic group:A drug reducing the secretion of the glands of the stomach proton pump inhibitor

ATX: & nbsp

A.02.B.C Proton pump inhibitors

A.02.B.C.04 Rabeprazole

Pharmacodynamics:

Mechanism of action. Rabeprazole belongs to the class of antisecretory substances, derivatives of benzimidazole. Suppresses the secretion of gastric juice by specific inhibition of H⁺/TO⁺ -ATP-ase on the secretory surface of parietal cells of the stomach. It blocks the final stage of hydrochloric acid secretion, reducing the content of basal and stimulated secretion, regardless of the nature of the stimulus.

Possessing high lipophilicity easily penetrates into the parietal cells of the stomach, concentrates in them, providing a cytoprotective action and increasing the secretion of bicarbonate.

Antisecretory activity. After oral administration of 20 mg of rabeprazole, antisecretory action occurs within 1 hour and reaches a maximum after 2-4 hours; inhibition of basal and stimulated food secretion of acid 23 hours after the first dose of rabeprazole is 62% and 82% respectively, and lasts up to 48 hours. At the termination of reception secretory activity is restored within 1-2 days.

Effect on the concentration of gastrin in the blood plasma. In the first 2-8 weeks of therapy with rabeprazole, the concentration of gastrin in the blood plasma increases, which is a reflection of the inhibitory effect on the secretion of hydrochloric acid, and returns to the baseline level usually within 1-2 weeks after discontinuation of treatment.

Other effects. Does not have anticholinergic properties, does not affect the central nervous system (CNS), cardiovascular and respiratory systems. Against the background of taking rabeprazole, stable changes in the morphological structure of enterochromaxin-like cells, in the degree of gastritis, in the frequency of atrophic gastritis, intestinal metaplasia, or the spread of infection Helicobacter pylori not detected.

Pharmacokinetics:

Absorption. Rabeprazole quickly absorbed from the intestine, and its maximum concentrations in the plasma are reached about 3.5 hours after taking a dose of 20 mg. Changes in maximum concentrations (FROMmOh) and the values of the area under the curve "concentration-time" (AUC) Rabeprazole are linear in the dose range of 10 to 40 mg. Absolute bioavailability after oral administration of 20 mg (compared with intravenous administration) is about 52%. In addition, the bioavailability does not change with multiple administration of rabeprazole. In healthy volunteers, the half-life (T1 / 2) from the plasma is about 1 hour (varying from 0.7 to 1.5 hours), and the total clearance is 3.8 ml / min / kg.

In patients with chronic liver disease AUC increased by half compared to healthy volunteers, which indicates a decrease in the metabolism of the first passage, and the half-life (T1 / 2) of plasma 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 food slows the absorption of rabeprazole by 4 hours or more, but neither FROMmOh, neither the degree of absorption is changed.

Distribution. In humans, the degree of binding of rabeprazole to plasma proteins is about 97%.

Metabolism and excretion. After taking a single oral dose of 20 mg ¹⁴C-labeled rabeprazole unchanged drug in the urine was found. About 90% of rabeprazole is excreted in the urine mainly in the form of two metabolites: the conjugate of mercapturic acid (M5) and carboxylic acid (MB), and also in the form of two unknown metabolites detected during the toxicological analysis. The rest of the accepted rabeprazole sodium is excreted with feces.

The total excretion is 99.8%. These data indicate a slight excretion of metabolites of rabeprazole sodium with bile. The main metabolite is thioether (M1). The only active metabolite is desmethyl (M3), but it was observed in low concentration only in one participant in the study after taking 80 mg of rabeprazole.

Terminal stage of renal failure

In patients with stable renal insufficiency in the terminal stage, which require maintenance hemodialysis (creatinine clearance <5 ml / min / 1.73 m²), the removal of rabeprazole is similar to that of healthy volunteers. AUC and C max in these patients were approximately 35% lower than in healthy volunteers. On average, T1 / 2 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.

Chronic compensated cirrhosis

Patients with chronic compensated cirrhosis are well tolerated rabeprazole in a dose of 20 mg once a day, although AUC doubled and C_m_Oh 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 elderly patients AUC was about twice as large, and C_m_Oh increased by 60% compared to young healthy volunteers. However, there were no signs of cumulation of rabeprazole.

CYP2C19 polymorphism

In patients with delayed metabolism CYP2C19 after 7 days of taking rabeprazole at a dose of 20 mg per day AUC increases in 1,9 times, and the half-life is 1,6 times as compared with the same parameters for "fast metabolizers," while FROMmOh increases by 40%.

Indications:

- Stomach ulcer in the phase of exacerbation and ulcer of anastomosis;

- peptic ulcer of duodenum in the stage of exacerbation;

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

- maintenance therapy of gastroesophageal reflux disease;

- non-erosive 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 disease.

Contraindications:

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

- pregnancy;

- the period of breastfeeding;

- children under 18 years old, except for gastroesophageal reflux disease - children under 12 years;

- deficiency of lactase;

- lactose intolerance;

- glucose-galactose malabsorption.

Carefully:

Severe renal insufficiency, severe hepatic insufficiency, children's age.

Pregnancy and lactation:

There are no data on the safety of rabeprazole during pregnancy. Studies of reproductive performance in rats and rabbits showed no signs of impaired fertility or fetal developmental defects caused by rabeprazole; However, in rats in small quantities, the drug penetrates the placental barrier. Rabeprazole should not be used during pregnancy, except when the expected positive effect for the mother exceeds the possible harm to the fetus.

It is not known whether rabeprazole with breast milk. Appropriate studies on the use of the drug in the period of breastfeeding have not been conducted. At the same time rabeprazole It is found in the milk of lactating rats, and therefore the drug can not be used in women during breastfeeding.

Dosing and Administration:

Tablets are taken internally as a whole, without chewing or grinding. The time of day and food intake do not affect the activity of rabeprazole.

Adults

With peptic ulcer in the stage of exacerbation and ulcer of anastomosis it is recommended to take 10-20 mg once a day. Usually the course of therapy is 6 weeks, in some cases the duration of treatment can be increased by another 6 weeks.

With duodenal ulcer in the acute stage it is recommended to take 10-20 mg once a day. 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 and ulcerative gastroesophageal reflux disease (GERD) or reflux esophagitis it is recommended to take 10-20 mg once a day. Duration of treatment is from 4 to 8 weeks. If necessary, the duration of treatment can be increased by another 8 weeks.

With maintenance therapy of gastroesophageal reflux disease (GERD) it is recommended to take 10-20 mg once a day. The duration of treatment depends on the patient's condition.

With non-erosive gastroesophageal reflux disease (NERD) it is recommended to take 10-20 mg once a day. If after four weeks of treatment the symptoms do not disappear, an additional examination of the patient should be carried out. After relief of symptoms should take the drug at a dose of 10 mg 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 in a dose of up to 100 mg per day for a single dose or 60 mg twice a day. Treatment should continue as clinical need arises. In some patients with Zollinger-Ellison syndrome, the duration of treatment with rabeprazole was up to one year.

For eradication Helicobacter pylori it is recommended to take 20 mg twice a day according to a certain scheme with the appropriate combination of antibiotics. Duration of treatment is 7 days.

Patients with renal and hepatic insufficiency.

Patients with renal insufficiency correction of the dose is not required. In patients with mild and moderate hepatic insufficiency, the concentration of rabeprazole in the blood is usually higher than in healthy patients. Care should be taken when administering the drug to patients with severe hepatic impairment.

Elderly patients. Correction of the dose is not required.

Children. The safety and efficacy of rabeprazole in children aged 12 years and older is established for short-term (up to 8 weeks) treatment of gastroesophageal reflux disease. The recommended dose for children aged 12 years and older is 20 mg once a day for up to 8 weeks. The safety and efficacy of rabeprazole for use in other indications is not established for pediatric patients.

Side effects:

To determine the incidence of side effects of the drug, the following classification is very often used (≥ 1/10); often (≥ 1/100 and <1/10); infrequently (≥ 1/1000 and <1/100); rarely (≥ 1/10000 and <1/1000); very rarely (<1/10000); frequency is unknown (can not be estimated from available data).

Infectious and parasitic diseases:

often: infection.

Violations from the blood and lymphatic system:

rarely: neutropenia, leukopenia, thrombocytopenia, leukocytosis.

Immune system disorders:

rarely: hypersensitivity (facial swelling, erythema), acute systemic allergic reactions.

Disorders from the metabolism and nutrition:

rarely: anorexia;

frequency unknown: hyponatremia, hypomagnesemia (with prolonged use).

Disorders from the psyche and the nervous system:

often: insomnia;

infrequent: increased excitability;

rarely: headache, dizziness, drowsiness, weakness, depression; frequency is unknown: confusion.

Disorders from the side of the organ of vision:

rarely: impaired vision.

Vascular disorders:

frequency unknown: peripheral edema.

Disturbances from the respiratory system, chest and mediastinal organs:

often: cough, pharyngitis, rhinitis; infrequently: bronchitis, sinusitis.

Disorders from the gastrointestinal tract:

often: diarrhea, nausea, vomiting, abdominal pain, constipation, flatulence, glandular polyps of the bottom of the stomach (benign);

infrequently: indigestion, dryness of the oral mucosa, eructation;

rarely: gastritis, stomatitis, taste change;

frequency unknown: microscopic colitis.

Disorders from the liver and bile ducts:

rarely: hepatitis, jaundice.

Disorders from the rut and subcutaneous tissues:

infrequent: skin rash, erythema;

rarely: skin itching, increased sweating, bullous reactions;

very rarely: erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome;

frequency unknown: subacute cutaneous lupus erythematosus (PCV).

Disturbances from the musculoskeletal and connective tissue:

often: nonspecific pain, back pain;

infrequently: myalgia, arthralgia, cramps of the calf muscles.

Disorders from the kidneys and urinary tract:

infrequently: urinary tract infections;

rarely: interstitial nephritis.

Violations of the genitals and breast:

frequency unknown: gynecomastia.

General disorders and disorders at the site of administration:

often: asthenia, flu-like syndrome;

infrequently: chest pain, chills, fever.

Laboratory and instrumental data:

infrequently: increased activity of "hepatic" enzymes;

rarely: weight gain.

When taking proton pump inhibitors, an increased risk of fracture may occur.

Overdose:

Symptoms

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

Treatment

Specific antidote for the drug is unknown. Rabeprazole binds well to plasma proteins, and therefore is poorly excreted by dialysis. In case of an overdose, symptomatic and supportive treatment should be performed.

Interaction:

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

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 stomach environment. In healthy volunteers, the use of rabeprazole caused a decrease in the concentration of ketoconazole in the blood plasma by 33% and an increase in the minimum digoxin concentration by 22%. With simultaneous admission, it is necessary to adjust the dose of ketoconazole, digoxin or other drugs, the absorption of which depends on the acidity of the stomach.

Rabeprazole, like all drugs that block the secretion of acid, can reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be considered in patients with a reduced supply of vitamin B12 in the body or with risk factors for impaired absorption of vitamin B12 for prolonged therapy or in the presence of appropriate clinical symptoms.

It is not recommended simultaneous application of rabeprazole with atazanavir, since the effects of atazanavir are significantly reduced. Rabeprazole inhibits metabolism cyclosporine. Simultaneous administration of proton pump inhibitors (PPI) and methotrexate may lead to an increase in the concentration of methotrexate and / or its metabolite hydroxymototrexate and increase the half-life.

With the simultaneous use of rabeprazole and clarithromycin indicators AUC and Cmof rabeprazole increased by 11% and 34%, respectively, a AUC and Cmof 14-hydroxyclarithromycin (the active metabolite of clarithromycin) increased by 42% and 46%, respectively. This increase in exposure indices for rabeprazole and clarithromycin was not clinically significant.

Special instructions:

Before and after treatment, endoscopic control is necessary to exclude malignant neoplasm, because treatment can mask the symptoms and postpone the correct diagnosis.

Tablets of rabeprazole can not be chewed or crushed. Tablets should be swallowed whole. It has been established that neither the time of day nor the intake of food affects the activity of rabeprazole.

In a special study in patients with mild or moderate liver function abnormalities, there was no significant difference in the frequency of side effects of rabeprazole from that of the healthy and well-chosen for the sex and age, but nevertheless, caution should be exercised in the first administration of the drug to patients with severe impairment of function liver.

Patients with impaired renal or hepatic function, dose adjustment rabeprazole not required. AUC Rabeprazole sodium in patients with severe impaired liver function is approximately twice as high as in healthy patients.

Hypomagnesemia

In the treatment of IPP for at least 3 months, in rare cases, cases of symptomatic or asymptomatic hypomagnesemia were noted.In most cases, these reports were received one year after the therapy. Serious side effects were tetany, arrhythmia and convulsions. Most patients required treatment of hypomagnesemia, including magnesium substitution and cancellation of PPI. In patients who will receive long-term treatment or who take PPI with drugs such as digoxin or drugs that can cause hypomagnesemia (eg, diuretics), health workers should control the concentration magnesium before the initiation of IPP treatment and during treatment.

Patients should not take concomitantly with the drug rabeprazole other agents that reduce acidity, for example, H2-histamine receptor blockers or proton pump inhibitors.

Fractures of bones

STI therapy may increase the risk of osteoporosis-related fractures of the hip, wrist, or spine. The risk of fractures is increased in patients who received high doses of PPI for a long time (a year or more).

The simultaneous use of rabeprazole with methotrexate

According to the literature data, simultaneous reception of PPI with methotrexate (especially in high doses) may lead to an increase in the concentration of methotrexate and / or its metabolitehydroxymototrexate and increase the half-life. which can lead to toxicity of methotrexate. If it is necessary to use high doses of methotrexate, the possibility of temporary discontinuation of PPI therapy may be considered.

Infections, caused by Salmonella, Campylobacter and Clostridium difficile

Therapy PPI can lead to an increased risk of gastrointestinal infections, such as infections caused by Salmonella, Campylobacter and Clostridium difficile.

Effect on the ability to drive transp. cf. and fur:Proceeding from the peculiarities of pharmacodynamics of rabeprazole and its profile of undesirable effects, it is unlikely that rabeprazole has an impact on the ability to manage vehicles, mechanisms. However, in case of drowsiness, these activities should be avoided.

Form release / dosage:

Tablets are enteric, coated with 10 mg and 20 mg.

Packaging:

For 14 tablets in a contour mesh package.

1, 2 contoured cell packs together with instructions for use are 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-004797

Date of registration:13.04.2018

Expiration Date:13.04.2023

The owner of the registration certificate:TATHIMFARMPREPARATY, JSC TATHIMFARMPREPARATY, JSC Russia

Manufacturer: & nbsp

TATHIMFARMPREPARATY, JSC Russia

Information update date: & nbsp15.05.2018

Illustrated instructions

Instructions

Rabeprazole (Rabeprazol)