Rabiet® (Rabiet®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Dosage form: & nbspenteric-coated capsules
Composition:

1 capsule contains:

rabeprazole, substance-pellets 8.5% 118 mg active substance: rabeprazole sodium 10 mg;

Excipients: sugar spheres (sucrose 99.83%, novidone 0.17 %) 71.46 mg, sodium carbonate 1.66 mg, talc 1.77 mg, titanium dioxide 0.83 mg, hypromellose 14.75 mg;

auxiliary substances for the pellet shell: hypromellose phthalate 15.94 mg, cetyl alcohol 1.59 mg;

hard gelatin capsule №3: capsule body - titanium dioxide 2%, gelatin up to 100%; lid capsule - titanium dioxide 2%, dye blue patented 0.0176%, dye diamond black 0.0051%, gelatin to 100%.


Description:

Hard gelatin capsules No. 3 with a white body and a blue lid. The contents of the capsules are spherical pellets from almost white to white with a creamy or yellowish hue of color.

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

Mechanism of action

Rabeprazole sodium belongs to the class of antisecretory compounds, derivatives of benzimidazole. Rabeprazole sodium suppresses the secretion of gastric juice by specific inhibition of H+/TO+ ATPase on the secretory surface of parietal cells of the stomach. H + /'TO+ ATPase is a protein complex that functions as a proton pump, 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 suppression of both basal and stimulated acid secretion irrespective of the stimulus. Rabeprazole sodium does not possess anticholinergic properties.

Antisecretory action

After oral administration of rabeprazole sodium at a dose of 20 mg, the antisecretory effect develops within 1 hour. The 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 the predicted half-life (T1 / 2) (approximately 1 hour). This effect can be explained by prolonged binding of the drug substance to the H + / K + 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, secretory activity is restored within 1-2 days.

Effect on the level of gastrin in the blood plasma

In clinical trials, patients took 10 or 20 mg of rabeprazole sodium daily for up to 43 months. The concentration of gastrin in the blood plasma was increased in the first 2-8 weeks, which reflects the inhibitory effect on the secretion of acid. The concentration of gastrin returned to baseline usually within 1-2 weeks after discontinuation of treatment.

Effect on enterochromaffin-like cells

In the study of human stomach biopsy specimens from the antrum and stomach bottom area, 500 patients who received rabeprazole sodium or a reference preparation for 8 weeks, stable changes in the morphological structure of enterochromafin-like cells, the degree of gastritis, the frequency of atrophic gastritis, intestinal metaplasia, or the spread of infection Helicobacter pylori not detected.

In a study involving more than 400 patients who received 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 was recorded.

Other effects

The systemic effects of rabeprazole sodium on the central nervous system, cardiovascular or respiratory systems are not currently detected. It was shown that rabeprazole sodium at oral intake at a dose of 20 mg for 2 weeks does not affect the function of the thyroid gland, carbohydrate metabolism, the concentration of parathyroid hormone in the blood, and the concentration of cortisol, estrogens, testosterone, prolactin, glucagon, follicle stimulating hormone (FSH), luteinizing hormone (LH), renin, aldosterone and growth hormone.

Pharmacokinetics:

Suction

Rabeprazole is rapidly absorbed from the intestine, and its maximum concentrations in the blood plasma are reached approximately 3.5 hours after taking a dose of 20 mg. Change in maximum concentrations in blood plasma (Cmax) of the area values ​​under the "concentration-time" curve (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, bioavailability does not change with multiple administration of rabeprazole.In healthy volunteers, the period of zero-elimination 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 lesions liver AUC increased by half compared with healthy volunteers, which indicates a decrease in the metabolism of the first passage, and the half-life of the blood 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 a greasy beggar slows the absorption of rabeprazole by 4 hours or more, but neither CmOh, nor the degree of absorption is changed.

Distribution

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

Metabolism

In healthy people. After receiving a single oral dose of 20 mg of 14C-labeled rabeprazole sodium, an unchanged drug in the urine was found. About 90 % Rabeprazole is excreted through the kidneys mainly in the form of two metabolites: a conjugate of mercapturic acid (M5) and a carboxylic acid (M6), and also in the form of two unknown metabolites detected during toxicological analysis. The rest of the accepted rabeprazole sodium is excreted through the intestine.

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), removal of rabeprazole sodium is similar to that of healthy volunteers. AUC and FROMmax the of these patients were approximately 35% lower than in healthy volunteers. On average, the half-life of rabeprazole was 0.82 h in healthy volunteers; 0.95 h - in patients during hemodialysis and 3.6 h 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 transfer rabeprazole sodium in a dose of 20 mg I once a day, although AUC doubled and Cmax increased by 50% compared with healthy volunteers of the corresponding sex.

Elderly patients. In elderly patients, the elimination of rabeprazole is somewhat slowed down. After 7 days of taking rabeprazole but 20 mg per day in the elderly AUC was about twice as large, and Cmax 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 by 1.9 times, and half-life - by 1.6 times compared with the same parameters for "fast metabolizers," while FROMmax increases at 40 %.

Indications:

Symptoms of dyspepsia associated with increased acidity of gastric juice, incl. symptoms of gastroesophageal reflux disease (heartburn, acidic eructation).

Contraindications:

hypersensitivity to rabeprazole, substituted benzimidazoles or to the accessory components of the drug

pregnancy;

the period of breastfeeding;

age to 18 years;

deficiency of sugar / isomaltase, intolerance to fructose, glucose-galactose malabsorption.


Carefully:

Severe kidney failure.

Pregnancy and lactation:

Pregnancy

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, the drug penetrates small amounts through the placental barrier. The drug Rabiet® Do not use if you are pregnant, except when the expected positive effect on the mother exceeds the possible risk to the fetus.

Breast-feeding

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

Dosing and Administration:Inside, in a dose of 10 mg once a day.

Capsules can not be chewed or crushed. Capsules should be swallowed whole. It is recommended to take the drug in the morning, before taking the nurse. It has been established that neither the time of day nor the intake of food affects the activity of rabeprazole sodium, but the recommended time of taking the drug rabeprazole contributes to better adherence to patients treatment regimens.

In the absence of effect during the first three days of treatment, a specialist examination is necessary. The maximum course of treatment without a doctor's consultation is 14 days.

With gastric ulcer in the acute stage and ulcer anastomobehind recommended take inside 20 mg once a day. Usually, the cure comes after 6 weeks of therapy, but in some cases the duration of treatment can be increased by another 6 weeks.

PIn peptic ulcer of the duodenumand in the stage of exacerbation it is recommended to take inside 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 gastroesophageal reflux disease or reflux esophagitis it is recommended to take inside 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 pedules.

With maintenance therapy of gastroesophageal reflux disease P'EERB) it is recommended to take inside but 20 mg once a day.The duration of treatment depends on the patient's condition.

PIn non-erosive gastroesophageal reflux disease (PEER) without esophagitis it is recommended to take inside 20 mg 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. dOzu is selected individually. The initial dose is 60 mg per day, then the dose is increased and the drug is given in 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 preferred. Treatment should continue as clinical need arises. In some patients with Zollinger-Alison syndrome, the duration of treatment with rabeprazole was up to one year.

For eradication Helicobacter pylori it is recommended to take inside 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

Dose adjustments in patients with renal insufficiency are not required.

In patients with mild to moderate hepatic insufficiency, the concentration of rabeprazole in the blood is usually higher than in healthy patients.

With the appointment of the drug Rabiette® Care should be taken in patients with severe hepatic impairment.

Elderly patients

Correction of the dose is not required.

Children

The safety and efficacy of 20 mg rabeprazole sodium for short-term (up to 8 weeks) treatment of GERD in children aged 12 years or more is confirmed by extrapolation of the results of adequate and well-controlled studies that support the efficacy of rabeprazole sodium for adults and safety studies and pharmacokinetics for pediatric patients. The recommended dose for children aged 12 years and over is 20 mg once a day for up to 8 weeks.

The safety and efficacy of rabeprazole sodium for the treatment of GERD in children under the age of 12 has not been established. The safety and efficacy of rabeprazole sodium for use in other indications is not established for pediatric patients.

Side effects:

Based on the experience of clinical studies, it can be concluded that rabeprazole usually well tolerated by patients. Side effects are generally mild or moderate and of a transient nature.

When taking rabeprazole in clinical trials, the following side effects were noted: headache, abdominal pain, diarrhea, flatulence, constipation, dry mouth, dizziness, rash, peripheral edema.

In the course of post-marketing use of the drug, the following side effects were reported: increased activity of "liver" enzymes, rarely - hepatitis and jaundice. Patients with cirrhosis of the liver rarely reported the development of hepatic encephalopathy. In rare cases, thrombocytopenia and neutropenia were noted. leukopenia, bullous eruptions, urticaria, acute systemic allergic reactions, myalgia, arthralgia, hypomagnesemia. Very rarely reported on the development of interstitial nephritis, gynecomastia, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome. Changes in other laboratory parameters during the use of rabeprazole sodium were not observed.

According to post-marketing surveillance data, an increase in the risk of fracture may occur with the use of PPIs (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 for rabeprazole is unknown. Rabeprazole binds well to blood plasma proteins, and is therefore poorly excreted by dialysis. In case of an overdose, symptomatic and supportive treatment should be performed.

Interaction:

Cytochrome 450 system

Rabeprazole sodium, like other inhibitors of the purging pump (IPN), is metabolized with the participation of the cytochrome P450 system (CYP450) in the liver. In studies in vitro on human liver microsomes it was shown that rabeprazole sodium is metabolized by isoenzymes CYP2C19 and CYP3A4.

Studies in healthy volunteers have shown that rabeprazole sodium does not have pharmacokinetic or clinically significant interactions with drugs that are being restabilized by the cytochrome P450 system - warfarin, faeitol, gsofillin and diazepam (regardless of whether the patients were metabolized diazepam intensely or weakly).

A study of combination therapy with antibacterial drugs was conducted. This quadripartite study involved 16 healthy volunteers who received 20 mg of rasprazole, 1000 mg of amoxicillin, 500 mg of clarithromycia, or a combination of these three drugs (PAK- rabeprazole, amoxicillin, clarithromycin). Indicators AUC and Cmax for clarithromycin and amoxicillin were similar when comparing combined therapy with monotherapy. Indicators AUC and Cmax for rabsprazole increased by 11% and 34%, respectively, and for 14-hydroxyclarithromycin (the active metabolite of clarithromycin) AUC and Cmax increased by 42% and 46%, respectively, for combination therapy compared with monotherapy. This increase in the indices of rabeprazole and clarithromycia was not clinically significant.

Interactions due to inhibition of gastric juice secretion

Rabeprazole sodium provides a stable and prolonged suppression of gastric juice secretion. Thus, interaction with substances for which the absorption depends on pH can occur. At simultaneous reception with rabeprazole sodium absorption of ketoconazole decreases by 30%, and absorption of digoxin increases by 22%.Therefore, some patients should be monitored to decide whether dose adjustment is necessary while taking sodium rabeprasol with ketoconazole, digoxin, or other drugs for which absorption is pH dependent.

Atazanavir

With the simultaneous administration of atazanavir 300 mg / ritonavir 100 mg with omeprazole (40 mg once a day) or atazanavir 400 mg with lansoprazole (60 mg once a day), a significant reduction in the impact of atazanavir was observed in healthy volunteers. Absorption of atazanavir depends on pH. Although simultaneous use with rabeprazole has not been studied, similar results are also expected for proton pump inhibitors. Thus, concomitant administration of atazanavir with proton pump inhibitors is recommended, including rabeprazole.

Antacid agents

In clinical trials, antacid substances were used in conjunction with rabeprazole sodium. Clinically significant interactions of rabeprazole sodium with aluminum hydroxide gel or magnesium hydroxide were not observed.

Food intake

In the clinical study, during the reception of rabeprazole sodium with depleted fat, clinically significant interactions with ns were observed.Reception of rabeprazole sodium simultaneously with enriched food can slow the absorption of rabeprazole up to 4 hours or more, however, Cmax and AUC do not change.

Cyclosporin

Experiments in vitro using a human liver macro showed that rabeprazole inhibits the metabolism of cyclosporine with IC50 62 μmol, i.e. in 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

According to reports of adverse events, published pharmacokinetic studies and retrospective analysis data, simultaneous administration of IPN and methotrexate (especially in high doses) can lead to an increase in the concentration of methotrexate and / or its metabolite, hydroxymothotrexate, and prolong the time of its removal. Nevertheless, special studies of drug interactions of methotrexate with IPN not carried out.

Special instructions:

The patient's response to the therapy with rabeprazole sodium ns excludes the presence of malignant neoplasms in the stomach.

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

In a special study in patients with mild or moderate impairment liver function, there was no significant difference in the frequency of side effects of rabeprazole from that of the healthy individuals selected by sex and age, but in spite of it is advisable to use caution at the first appointment of the drug Rabiette® patients with severe impairment of liver function.

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

Hypomagnesemia

When treating proton pump inhibitors 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, convulsions.Most patients required the treatment of hypomagnesemia, including the replacement of magnesium and the abolition of proton pump inhibitors. In patients who will receive long-term treatment or who take proton pump inhibitors with drugs such as digoxin or drugs that can cause hypomagnesemia (eg, diuretics), health care providers should monitor the magnesium concentration before starting treatment with proton pump inhibitors and during treatment.

Patients should not take concomitantly with the drug Rabiette® patients with severe impairment of liver function. other agents that reduce acidity, for example, H2-histamine receptor blockers or proton pump inhibitors.

Fractures of bones

According to observational studies, it can be assumed that proton pump inhibitor (PPI) therapy may lead to an increased risk of osteoporotic fractures of the hip, wrist, or spine. The risk of fractures was increased in patients who received high doses IPN for a long time (a year or more). Under high doses, it should be understood that doses exceeding the recommended dose in the instructions.

The simultaneous use of rabeprazole with methotrexate

According to the published data, simultaneous reception of IPN with methotrexate (above all high doses) may lead to an increase in the concentration of methotrexate and / or its metabolite hydroxy-aminotrans-sate and prolong the time of its removal, which may lead to toxicity of methotrexate. If it is necessary to use high doses of methotrexate, the possibility of temporary discontinuation of PID therapy may be considered.

Clostridium difficile

IPT therapy can lead to an increased risk of gastrointestinal infections, such as Clostridium difficile.

Patients receiving rabeprazole for a short-term symptomatic treatment of manifestations of GERD and NERD (eg, heartburn) without a prescription, you should consult a doctor in the following cases:

  • use of funds to relieve symptoms of heartburn and indigestion for 4 weeks or more;

  • the appearance of new symptoms or a change in previously observed symptoms in patients over 55 years of age;

  • cases of unintended decrease in body weight, anemia, bleeding in the gastrointestinal tract, dysphagia, pain during swallowing, constant vomiting or vomiting with blood and epigastric contents, cases of stomach ulcers or stomach operations in history, jaundice, etc. (including a violation of the function of baking and kidneys).

Patients with recurring symptoms of digestive disorders or heartburn should be observed regularly by the doctor. Patients aged over 55 years. daily taking over-the-counter drugs to relieve the symptoms of heartburn and indigestion should inform their doctor about this.

Patients ns should take concomitantly with rabeprazole other agents that reduce acidity, for example, H2-histamine receptor blockers or proton pump inhibitors.

When using other medications, patients should consult a pharmacist or physician before starting therapy with a non-prescription drug Raabit.

Patients should inform the doctor before using Rabiette®, if they are assigned an endoscopic examination.

You should avoid taking the drug Rabiette® before carrying out the urea breath test.

Patients with severe impairment of liver function should consult a doctor before starting therapy with Rabiette®, over-the-counter, for short-term symptomatic treatment of manifestations of GERD and NERD (for example, heartburn).

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

Based on the features of pharmacodynamics of rabeprazole and its profile of undesirable effects, it is unlikely that rabeprazole has an impact on the ability to drive vehicles and manage machinery. However, in the event of snotty, these activities should be avoided.

Form release / dosage:

Capsules intestine soluble 10 mg.


Packaging:

By 5, 7, 10, 14, 15, 20 or 30 capsules in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 1, 2, 3 contour squares, together with instructions for use, are placed in a pack of cardboard.

Storage conditions:

Store in a dry, dark place 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 printed on the package.
Terms of leave from pharmacies:Without recipe
Registration number:LSR-008784/10
Date of registration:26.08.2010
The owner of the registration certificate:OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia
Manufacturer: & nbsp
Information update date: & nbsp06.04.2015
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