Rabiet capsules 20mg №28

Composition

1 capsule contains:

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

excipients for the shell of pellets: hypromellose phthalate 15.94 mg, cetyl alcohol 1.59 mg;

hard gelatin capsule No. 3: capsule body - titanium dioxide 2%, gelatin up to 100%; the cap of the capsule is titanium dioxide 2%, blue patented dye 0.0176%, brilliant black dye 0.0051%, gelatin up to 100%.

pharmachologic effect

Rabeprazole sodium, the active component of Rabiet, belongs to the class of antisecretory compounds benzimidazole derivatives. It inhibits the secretion of gastric juice by specifically inhibiting 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 a proton pump inhibitor in the stomach and blocks the final stage of acid production. This effect depends on the dose of rabeprazole and leads to the suppression of both basal and stimulated acid secretion, regardless of the stimulus. The drug does not have anticholinergic properties.

After ingestion of rabeprazole sodium at a dose of 20 mg, the antisecretory effect develops within 1 hour. Inhibition of basal and stimulated secretion of acid 23 hours after the first dose of rabeprazole sodium is 69% and 82%, respectively, and lasts up to 48 hours. Such a duration of pharmacodynamic action is much longer than predicted by the half-life (T1 / 2) (approximately 1 hour). This effect can be explained by 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. At the termination of reception, secretory activity is restored within 1-2 days.

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

In the study of biopsy specimens of a human stomach from the antrum and the bottom of the stomach, 500 patients treated with rabeprazole sodium or a comparison drug for 8 weeks, sustained changes in the morphological structure of enterochromine-like cells, degree of gastritis, frequency of atrophic gastritis, intestinal metaplasia or the spread of Helicobacter infection pylori not found.

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 frequency of hyperplasia was low and comparable to that for Omeprazole (20 mg / kg). Not a single case of adenomatous changes or carcinoid tumors was observed in rats.

Systemic effects of rabeprazole sodium on the central nervous system, the cardiovascular or respiratory systems are not currently fixed. It was shown that orally administered rabeprazole sodium at a dose of 20 mg for 2 weeks does not affect thyroid function, carbohydrate metabolism, the concentration of parathyroid hormone in the blood, as well as the concentration of cortisol, estrogen, testosterone, prolactin, glucagon follicle-stimulating hormone (FSG ), luteinizing hormone (LH), renin, aldosterone and somatotropic hormone.

Indications

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

- duodenal ulcer in the acute phase;

- erosive and ulcerative gastroesophageal reflux disease or reflux esophagitis;

- supportive 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 the eradication of Helicobacter pylori in patients with peptic ulcer.

Contraindications

- deficiency of sucrase / isomaltase, fructose intolerance, glucose-galactose malabsorption syndrome;

- pregnancy;

- breastfeeding period;

- age up to 18 years;

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

Precautions should be prescribed the drug for severe renal failure.

Side effects

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

When using rabeprazole in clinical studies, the following side effects were noted.

From the nervous system: headache, dizziness.

On the part of the digestive system: abdominal pain, diarrhea, flatulence, constipation, dry mouth.

Other: rash, peripheral edema.

During the post-registration use of the drug, the following side effects were reported.

On the part of the digestive system: increased activity of liver enzymes; rarely - hepatitis, jaundice. Hepatic encephalopathy has been reported rarely in patients with cirrhosis.

From the hematopoietic system: rarely - thrombocytopenia, neutropenia, leukopenia.

On the part of the musculoskeletal system: rarely - myalgia, arthralgia.

Allergic reactions: rarely - bullous rash, urticaria, acute systemic allergic reactions; very rarely - erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome.

Other: rarely - hypomagnesemia; very rarely - the development of interstitial nephritis, gynecomastia.

Changes in other laboratory parameters during the reception of rabeprazole sodium was not observed.

According to post-marketing surveillance data when taking proton pump inhibitors, the risk of fractures may increase.

Interaction

Cytochrome 450 System

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

Studies on healthy volunteers showed that rabeprazole sodium does not have pharmacokinetic or clinically significant interactions with drugs that are metabolized by the cytochrome P450 system — Warfarin, phenytoin, theophylline, and diazepam (regardless of how the diazepam is metabolized in patients, strongly or weakly).

A study of combination therapy with antibacterial drugs was conducted.This quadrilateral study involved 16 healthy volunteers who received 20 mg of rabeprazole, 1000 mg of Amoxicillin, 500 mg of Clarithromycin, or a combination of these three drugs (RAK - rabeprazole, amoxicillin, clarithromycin). The AUC and C max values ​​for clarithromycin and amoxicillin were similar when comparing combination therapy with monotherapy. AUC and Cmax for rabeprazole increased by 11% and 34%, respectively, and for 14-hydroxylaritromycin (the active metabolite of clarithromycin), AUC and Cmax increased by 42% and 46% for combination therapy compared to monotherapy, respectively. This increase in the effects of rabeprazole and clarithromycin was not recognized as clinically significant.

Interactions due to inhibition of secretion of gastric juice

Rabeprazole sodium provides sustained and prolonged suppression of the secretion of gastric juice. Thus, there may be interaction with substances for which absorption is pH dependent. When taken simultaneously with sodium rabeprazole, Ketoconazole absorption is reduced by 30% and Digoxin absorption increases by 22%. Therefore, some patients should be monitored to decide on the need for dose adjustment while simultaneously using rabeprazole sodium with ketoconazole, digoxin, or other drugs for which absorption is pH dependent.

Atazanavir

While taking atazanavir 300 mg / ritonavir 100 mg with omeprazole (40 mg 1 time / day) or atazanavir 400 mg with lansoprazole (60 mg 1 time / day), healthy volunteers showed a significant decrease in the effect of atazanavir. Absorption of atazanavir is pH dependent. Although co-administration with rabeprazole has not been studied, similar results are also expected for proton pump inhibitors. Therefore, the simultaneous use of atazanavir with proton pump inhibitors, including rabeprazole, is not recommended.

Antacids

In clinical studies, antacid agents were used in conjunction with rabeprazole sodium. No clinically significant interaction of rabeprazole sodium with aluminum hydroxide gel or Magnesium hydroxide was observed.

Meal

In a clinical trial, there was no clinically significant interaction with rabeprazole sodium with a fat-poor diet. Intake of rabeprazole sodium at the same time as food enriched with fats may slow down the absorption of rabeprazole up to 4 hours or more, however, Cmax and AUC do not change.

Cyclosporine

In vitro experiments using human liver microsomes have shown that rabeprazole inhibits the cyclosporin metabolism with an IC50 of 62 μmol, i.e. at a concentration 50 times higher than C max for healthy volunteers after 20 days of taking rabeprazole at a dose of 20 mg. The degree of inhibition is similar to that of omeprazole for equivalent concentrations.

Methotrexate

According to reports of adverse events, published pharmacokinetic studies and data from a retrospective analysis, it can be assumed that the simultaneous use of proton pump inhibitors and Methotrexate (primarily in high doses) can lead to an increase in the concentration of methotrexate and / or its hydroxymetotrexate metabolite and prolong its clearance time. . However, special studies of drug interactions of methotrexate with proton pump inhibitors have not been conducted.

How to take, the course of administration and dosage

The drug is taken orally, preferably in the morning, before eating. It has been established that neither the time of the day nor food intake affects the activity of rabeprazole sodium, but the recommended time of administration of the drug rabeprazole contributes to better patient compliance with the treatment regimen. Capsules should be swallowed whole, not chewed or chopped.

The recommended dose is 10 mg 1 time / day.

If there is no effect during the first 3 days of treatment, a specialist should be examined.

The maximum course of treatment without consulting a doctor is 14 days.

Overdose

Data on intentional or accidental overdose is minimal. Cases of severe overdose of rabeprazole have not been reported.

Treatment: symptomatic and supportive therapy. The specific antidote for rabeprazole is unknown. Rabeprazole binds well to plasma proteins and is therefore poorly excreted during dialysis.

Use during pregnancy

There are no data on the safety of using rabeprazole during pregnancy. Reproductive studies in rats and rabbits showed no signs of impaired fertility or fetal developmental defects caused by rabeprazole; however, in rats, the drug in small amounts penetrates the placental barrier. The drug Rabiet® should not be used during pregnancy unless the expected positive effect on the mother outweighs the possible risk to the fetus.

It is not known whether rabeprazole is excreted in breast milk. Relevant studies in women during breastfeeding have not been conducted. At the same time, rabeprazole was found in the milk of lactating rats; therefore, Rabiet® should not be prescribed to women during breastfeeding.

Special instructions

The patient's response to therapy with rabeprazole sodium does not exclude the presence of malignant tumors in the stomach.

In a special study in patients with mild or moderate liver dysfunction, there was no significant difference in the incidence of side effects of rabeprazole from that in healthy individuals matched by gender and age, but despite this, caution is recommended when first using Rabiet® in patients with severe impaired liver function.

Patients with impaired renal or hepatic function do not require dose adjustment of Rabiet®. AUC of rabeprazole sodium in patients with severe liver dysfunction is about 2 times higher than in healthy patients.

Hypomagneemia

When treated with proton pump inhibitors for at least 3 months, in rare cases, there have been cases of symptomatic or asymptomatic hypomagnesemia. In most cases, these messages were received one year after the treatment. Serious side effects were tetany, arrhythmia, convulsions. Most patients required treatment for hypomagnesemia, including the replacement of magnesium and the abolition of proton pump inhibitors. Patients who will receive long-term treatment or who are taking proton pump inhibitors with drugs such as digoxin or drugs that can cause hypomagnesia (for example, diuretics) should monitor magnesium concentrations before starting treatment with proton pump inhibitors and during treatment.

It should not be taken simultaneously with the drug Rabiet® other agents that reduce acidity, for example, H2-histamine receptor blockers or proton pump inhibitors.

Bone fractures

According to observational studies, it can be assumed that therapy with proton pump inhibitors may lead to an increased risk of osteoporosis-related fractures of the hip, wrist, or spine.The risk of fractures was increased in patients who received proton pump inhibitors in high doses for a long time (a year or more). Under high should be understood doses higher than those recommended in the instructions.

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