Rabiet capsules enteric soluble 10mg, 14pcs

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;

solid gelatin capsule No. 3:

capsule body – titanium dioxide 2%,

gelatin up to 100%;

capsule cap-titanium dioxide 2%,

dye blue patent 0.0176%,

dye diamond black 0.0051%,

gelatin up to 100%.

Pharmacological action

Rabeprazole sodium, the active ingredient of Rabiet, belongs to the class of antisecretory compounds derived from benzimidazole. It suppresses gastric juice secretion by specifically inhibiting H+ / K+ ATPase on the secretory surface of gastric parietal cells. 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 depends on the dose of rabeprazole and leads to suppression of both basal and stimulated acid secretion, regardless of the stimulus. The drug does not have anticholinergic properties.

Antisecretory action

  After oral use of rabeprazole sodium at a dose of 20 mg, the antisecretory effect develops within 1 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 the predictable half-life (T 1/2) (approximately 1 hour).

This effect can be explained by the long-term binding of the drug substance to the H+/K+ ATPase of the parietal cells of the stomach. The inhibitory effect of rabeprazole sodium on acid secretion reaches a plateau after three days of taking rabeprazole sodium. Upon discontinuation of the drug, secretory activity is restored within 1-2 days.

Effect on the level of gastrin in blood plasma

  In clinical trials, patients received 10 or 20 mg of rabeprazole sodium daily for a treatment duration of 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 usually returned to baseline levels within 1-2 weeks after discontinuation of treatment.

Effect on enterochromaffin-like cells

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

  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). There were no cases of adenomatous changes or carcinoid tumors observed in rats.

Other effects

The systemic effects of rabeprazole sodium on the central nervous system, cardiovascular or respiratory systems are not currently documented. Rabeprazole sodium, when taken orally at a dose of 20 mg for 2 weeks, has no effect on thyroid function, carbohydrate metabolism, parathyroid hormone concentration in the blood, as well as cortisol, estrogen, testosterone, prolactin, follicle-stimulating hormone (FSH) glucagon, luteinizing hormone (LH), renin, aldosterone and somatotropic hormone.

Indications

— peptic ulcer in the acute phase and ulcer of the anastomosis;

— ulcer of the duodenum in the acute phase;

erosive and ulcerative gastroesophageal reflux disease or reflux esophagitis;

— maintenance therapy of gastroesophageal reflux disease;

— non-erosive gastroesophageal reflux disease;

syndrome zollingerellison and other States characterized by a pathological hypersecretion;

— in combination with appropriate antibacterial therapy for Helicobacter pylori eradication in patients with peptic ulcer disease.

Contraindications

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

– pregnancy;

– breast-feeding period

— – age up to 18 years;

– hypersensitivity to rabeprazole, substituted benzimidazoles or to auxiliary components of the drug.

With caution, the drug should be prescribed 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. Side effects are generally mild or moderate and transient.

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

Nervous system disorders:  headache, dizziness.

From the digestive system:  abdominal pain, diarrhea, flatulence, constipation, dry mouth.

Other services:  rash, peripheral edema.

The following side effects were reported during post-marketing use of the drug.

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

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

Musculoskeletal disorders:  rarely-myalgia, arthralgia.

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

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

No changes in other laboratory parameters were observed during rabeprazole sodium use.

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

Interaction

The cytochrome 450 system

Rabeprazole sodium, like other proton pump inhibitors, is metabolized by the cytochrome p450 (CYP450) system in the liver. In vitro studies on human liver microsomes have 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 how diazepam is metabolized in patients, heavily or weakly).

A study of combination therapy with antibacterial drugs was conducted. This four-way study included 16 healthy volunteers who received 20 mg of rabeprazole,1000 mg of amoxicillin,500 mg of clarithromycin, or a combination of these three drugs (CANCER – rabeprazole, amoxicillin, clarithromycin).

The AUC and Cmax values for clarithromycin and amoxicillin were similar when compared with combination therapy and monotherapy. The AUC and Cmax values for rabeprazole increased by 11% and 34%, respectively, and for 14-hydroxyclarithromycin (the active metabolite of clarithromycin), the AUC and Cmax values increased by 42% and 46%, respectively, for combination therapy compared to monotherapy. This increase in rabeprazole and clarithromycin exposure was not considered clinically significant.

Interactions due to inhibition of gastric juice secretion

Rabeprazole sodium provides stable and prolonged suppression of gastric juice secretion. Thus, interaction with substances for which absorption depends on pH can occur. When taken concomitantly with rabeprazole sodium, ketoconazole absorption decreases by 30%, and digoxin absorption increases by 22%. Therefore, some patients should be monitored to determine whether dose adjustment is necessary when rabeprazole sodium is co-administered with ketoconazole, digoxin, or other medications for which absorption depends on pH.

Atazanavir

Concomitant use of atazanavir 300 mg/ritonavir 100 mg with omeprazole (40 mg 1 time / day) or atazanavir 400 mg with lansoprazole (60 mg 1 time / day) in healthy volunteers, a significant reduction in exposure to atazanavir was observed. Absorption of atazanavir depends on pH. Although concomitant use with rabeprazole has not been studied, similar results are also expected for proton pump inhibitors. Therefore, concomitant use of atazanavir with proton pump inhibitors, including rabeprazole, is not recommended.

Antacids

In clinical studies, antacids were used together with rabeprazole sodium.No clinically significant interaction of rabeprazole sodium with aluminum hydroxide gel or magnesium hydroxide was observed.

Food intake

In a clinical study, no clinically significant interaction was observed during the use of rabeprazole sodium with a fat-depleted diet. Taking rabeprazole sodium concomitantly with a fat-rich diet may slow the absorption of rabeprazole for up to 4 hours or more, but Cmax and AUC do not change.

Cyclosporine

In vitro experiments using human liver microsomes have shown that rabeprazole inhibits cyclosporine metabolism with an IC50 of 62 micromol, i. e. at a concentration 50 times higher than the Cmax 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 at equivalent concentrations.

Methotrexate

According to reports of adverse events, published pharmacokinetic studies, and retrospective analysis, it can be assumed that concomitant use of proton pump inhibitors and methotrexate (especially at high doses) may lead to an increase in the concentration of methotrexate and/or its metabolite hydroxymethotrexate and prolong its elimination time. However, no specific studies have been conducted on the drug interaction of methotrexate with proton pump inhibitors.

How to take, course of use and dosage

The drug is taken orally, preferably in the morning, before meals. It was found that neither the time of day nor food intake affects the activity of rabeprazole sodium, but the recommended time of taking rabeprazole contributes to better compliance of patients with the treatment regimen. Capsules should be swallowed whole, without chewing or crushing.

The recommended dose is 10 mg 1 time/day.

If there is no effect during the first 3 days of treatment, a specialist examination is necessary.

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

Overdose

Data on intentional or accidental overdose are minimal.

There were no cases of severe overdose of rabeprazole.

Treatment: conducting symptomatic and supportive care.

The specific antidote for rabeprazole is unknown.

Rabeprazole binds well to plasma proteins, so it is poorly excreted during dialysis.

Special instructions

The patient’s response to rabeprazole sodium therapy does not exclude the presence of malignancies in the stomach.

In a special study in patients with mild or moderate hepatic impairment, there was no significant difference in the frequency of side effects of rabeprazole from those in healthy individuals selected by gender and age, but despite this, caution is recommended when using Rabiet® for the first time in patients with severe hepatic impairment.

In patients with impaired renal or hepatic function, adjust the dose of Rabiet® not required. The AUC of rabeprazole sodium in patients with severe hepatic impairment is approximately 2 times higher than in healthy patients.

Hypomagnesemia

When treated with proton pump inhibitors for at least 3 months, cases of symptomatic or asymptomatic hypomagnesemia have been reported in rare cases. In most cases, these reports were received one year after the therapy. Serious side effects were tetany, arrhythmia, seizures.

Most patients required treatment for hypomagnesaemia, including magnesium replacement and withdrawal of proton pump inhibitors. In patients who will be receiving long-term treatment or who are taking proton pump inhibitors with drugs such as digoxin or drugs that may cause hypomagnesemia (for example, diuretics), magnesium concentrations should be monitored before starting treatment with proton pump inhibitors and during treatment.

Do not take other acid-reducing agents, such as H2-histamine receptor blockers or proton pump inhibitors, at the same time as Rabiet®.

Bone fractures

Observational studies suggest that proton pump inhibitor therapy may increase the risk of osteoporosis-related hip, wrist, or spinal fractures. The risk of fractures was increased in patients who received high-dose proton pump inhibitors for a long time (one year or more). High doses should be understood as those that exceed those recommended in the instructions.

Concomitant use with methotrexate

According to literature data, concomitant use of proton pump inhibitors with methotrexate (primarily in high doses) can lead to an increase in the concentration of methotrexate and/or its metabolite hydroxymethotrexate and prolong the time of its elimination, which can lead to the manifestation of methotrexate toxicity. If it is necessary to use methotrexate in high doses, the possibility of temporarily stopping therapy with proton pump inhibitors may be considered.

Clostridium difficile

Proton pump inhibitor therapy may increase the risk of gastrointestinal infections, such as those caused by Clostridium difficile.

Patients taking rabeprazole for short-term symptomatic treatment of symptoms of GERD and NERD (such as heartburn) without a prescription should consult a doctor in the following cases::

the remedies for relieving symptoms of heartburn and indigestion for 4 weeks or more;

– the appearance of new symptoms or change in previously observed symptoms in patients aged more than 55 years;

– cases of unintentional reduction of body weight, anemia, gastrointestinal bleeding, dysphagia, pain on swallowing, constant vomiting or vomiting blood and stomach contents, cases of stomach ulcers, or stomach surgery, a history of jaundice, etc. (including the violation of the functions of the liver and kidneys).

Patients with recurrent symptoms of indigestion or heartburn should be regularly monitored by a doctor. Patients over the age of 55 who take daily over-the-counter medications to relieve symptoms of heartburn and digestive disorders should inform their doctor about this.

Other acid-reducing agents, such as H2-histamine receptor blockers or proton pump inhibitors, should not be used concomitantly with rabeprazole.

When using other medications, patients should consult their pharmacist or doctor before starting therapy with Rabiet® over-the-counter.

Patients should inform their doctor before starting over-the-counter use of Rabiet®if they are scheduled for an endoscopic examination.

Avoid taking Rabiet before performing a urea breath test.

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

Influence on the ability to drive motor vehicles and manage mechanisms

Based on the pharmacodynamic characteristics of rabeprazole and its undesirable effects profile, it is unlikely that rabeprazole affects the ability to drive vehicles and manage mechanisms. However, if drowsiness occurs, these activities should be avoided.

Storage conditions

 In a dark place, at a temperature not exceeding 25 °C.

Shelf life

2 years

Active ingredient

Rabeprazole

Dosage form

Capsules

Purpose

For children as prescribed by a doctor, For adults

Indications

Reflux esophagitis, Gastrointestinal infections caused by Helicobacter pylori, Heartburn, Stomach and duodenal ulcers