Rabelock pills 20mg, 28pcs

Composition

1 tablet contains:

Active ingredient: rabeprazole sodium 20 mg.

Excipients: mannitol 89.0 mg; magnesium oxide 80.0 mg; hypromellose 5.0 mg; microcrystalline cellulose 20.0 mg; starch 20.0 mg; carmellose 20.0 mg; talc 3.0 mg; magnesium stearate 6.0 mg; colloidal silicon dioxide 3.0 mg.

Shell: hypromellose 9.5 mg; propylene glycol 1.5 mg;

Enteric shell: methacrylic acid and ethyl acrylate copolymer (type C) (1: 1) 13.95 mg; polysorbate 80 0.209 mg; dibutyl phthalate 2.090 mg; sodium hydroxide 0.119 mg; iron oxide yellow dye 0.783 mg; talc 5.63 mg;titanium dioxide 1.210 mg

Pharmacological action

Pharmacotherapy group: a means of reducing the secretion of gastric glands-proton pump inhibitor.

ATX Code: A 02 BC 04

Pharmacologicalproperties

Pharmacodynamics

Mechanism of action

Rabeprazole sodium belongs to the class of antisecretory substances derived from benzimidazole. Rabeprazole sodium 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, so 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, regardless of the stimulus. Rabeprazole sodium has no anticholinergic properties.

Antisecretory action

After oral use 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 the predictable half-life (approximately one 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 plasma

In clinical trials, patients received 10 or 20 mg of rabeprazole sodium daily for a treatment duration of up to 43 months. Plasma gastrin levels were elevated during the first 2-8 weeks, reflecting an inhibitory effect on acid secretion.

Gastrin concentrations usually returned to baseline levels within 1-2 weeks after discontinuation of treatment.

Effect on enterochromafin-like cells

In the study of human gastric biopsy samples from the antrum and fundus of 500 patients treated with rabeprazole sodium or a reference drug for 8 weeks, no stable changes in the morphological structure of enterochromafine-like cells, the severity of gastritis, the frequency of atrophic gastritis, intestinal metaplasia, or the spread of Helicobacter Pylori infection were 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). There were no cases of adenomatous changes or carcinoid tumors observed in rats.

Other effects

Systemic effects of rabeprazole sodium on the central nervous system, cardiovascular or respiratory systems have not yet been detected.

Rabeprazole sodium, taken orally at a dose of 20 mg for 2 weeks, has been shown to have no effect on thyroid function, carbohydrate metabolism, blood levels of parathyroid hormone, as well as cortisol, estrogen, testosterone, prolactin, glucagon, follicle-stimulating hormone (FSH), luteinizing hormone (LH), renin, aldosterone and somatotropic hormone.

Pharmacokinetics

Absorption rate

Rabeprazole is rapidly absorbed from the intestine, and its peak plasma concentrations are reached approximately 3.5 hours after taking a dose of 20 mg. Changes in peak plasma concentrations (with_max) and the area under the concentration-time curve (AUC) of rabeprazole are linear in the dose range from 10 to 40 mg.

The absolute bioavailability after oral use of 20 mg (compared to intravenous use) is about 52%.

In addition, the bioavailability does not change with repeated use of rabeprazole. In healthy volunteers, the plasma half-life 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 damage, the AUC was doubled compared to healthy volunteers, which indicates a decrease in first-pass metabolism, and the plasma half-life was increased by 2-3 times.

Neither the time of taking the drug during the day, nor antacids do not affect the absorption of rabeprazole. Taking the drug with fatty foods slows down the absorption of rabeprazole for 4 hours or more, but neither with_{mab nor the}degree of absorption changes.

Distribution

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

Metabolism and elimination

In healthy people

After taking a single oral dose of 20 mg of 14C-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: conjugate of amercapturic acid (M5) and carboxylic acid (M6), as well as in the form of two unknown metabolites detected during toxicological analysis. The remainder of rabeprazole sodium is excreted in the faeces.

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

End-stage renal failure

In patients with stable end-stage renal insufficiency who require maintenance hemodialysis (creatinine clearance AUC and_cmax in these patients were approximately 35% lower than in healthy volunteers.

The mean half-life of rabeprazole was 0.82 hours in healthy volunteers,0.95 hours in patients during hemodialysis, and 3.6 hours after hemodialysis. Clearance of the drug in patients with kidney disease requiring hemodialysis was approximately twice as high as in healthy volunteers.

Chronic compensated cirrhosis

Patients with chronic compensated cirrhosis of the liver tolerate rabeprazole sodium at a dose of 20 mg once a day, although the AUC is doubled and with_max increased by 50% compared to healthy volunteers of the corresponding sex.

Elderly patients

In elderly patients, the elimination of rabeprazole is somewhat delayed. After 7 days of taking rabeprazole 20 mg per day, the AUC in elderly subjects was approximately twice as high, and with_maxincreased by 60% compared to young healthy volunteers. However, there were no signs of accumulation of rabeprazole.

CYP2C19 polymorphism

In patients with slow CYP2C19 metabolism, after 7 days of taking rabeprazole at a dose of 20 mg per day, the AUC increases by 1.9 times, and the half-life by 1.6 times compared to the same parameters in “fast metabolizers”, while with_max increases by 40%.

Indications

– Acute gastric ulcer and anastomotic ulcer;

– acute duodenal ulcer;

– erosive and ulcerative gastroesophageal reflux disease or reflux esophagitis;

-maintenance therapy of gastroesophageal reflux disease;

– non – erosive gastroesophageal reflux disease;

– Zollinger syndrome-Ellison’s disease and other conditions characterized by pathological hypersecretion.

As part of combination therapy:

– eradication of Helicobacter Pylori in patients with peptic ulcer disease.

Use during pregnancy and lactation

There are no data on the safety of rabeprazole use during pregnancy. Reproductive studies in rats and rabbits have shown no signs of fertility disorders or fetal defects caused by rabeprazole; however, in rats, small amounts of the drug penetrate the placental barrier.

Rabeloc® should not be used during pregnancy unless the expected positive effect for the mother exceeds the possible harm to the fetus.

It is not known whether rabeprazole is excreted in breast milk. No relevant studies have been conducted in lactating women. However, rabeprazole is found in the milk of lactating rats, and therefore Rabelok®should not be prescribed to nursing women.

Contraindications

Individual hypersensitivity to rabeprazole, substituted benzimidazoles or auxiliary components of the drug, pregnancy, breast-feeding, children under 12 years of age.

With caution

Severe renal insufficiency, severe hepatic insufficiency, children aged 12-18 years.

Side effects

Based on the experience of clinical trials, it can be concluded that rabeprazole is usually well tolerated by patients.Side effects, generally mild or moderate, are transient in nature. When taking rabeprazole in clinical studies, the following side effects were noted: headache, abdominal pain, diarrhea, flatulence, constipation, dry mouth, dizziness, rash, peripheral edema.

Adverse reactions are classified for each organ system using the following frequency classification: very common (>1/10); common (>1/100 and ><1/10); uncommon (>1/1000 and <1/10); uncommon (><1/100); rare (>1/10000 and <1/100); rare (><1/1000); very rare (

Immune system disorders: rarely-acute systemic allergic reactions.

Disorders of the blood and lymphatic system: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 rare – 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.

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

According to post-marketing observations, taking proton pump inhibitors (PPIs) may increase the risk of fractures, subacute cutaneous lupus erythematosus, and glandular polyps in the stomach (see section “Special instructions”). Rare reports of hepatic encephalopathy have been reported in patients with cirrhosis.

Interaction

The cytochrome 450 system

Rabeprazole sodium, like other proton pump inhibitors (PPIs), 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 the isoenzymes CYP2C19 and CYP3A4.

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 patients metabolize diazepam intensively or weakly).

A study of combination therapy with antibacterial drugs was conducted. This four-way cross – sectional 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 max}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-hydroxy-clarithromycin (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 exposure rates for rabeprazole and clarithromycin 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 decide whether to adjust the dose when taking rabeprazole sodium concomitantly with ketoconazole, digoxin, or other medications for which absorption depends on pH.

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) in healthy volunteers, a significant reduction in atazanavir exposure was observed.

Absorption of atazanavir depends on pH. Although concomitant use with rabeprazole has not been studied, similar results are expected for other proton pump inhibitors. Therefore, concomitant use of atazanavir with proton pump inhibitors, including rabeprazole, is not recommended.

Antacids

In clinical studies, antacid agents were used together with rabeprazole sodium. Clinically significant interactions of rabeprazole sodium with aluminum hydroxide gel or magnesium hydroxide were not observed.

Food intake

In a clinical study, no clinically significant interactions were 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, however, with_max and AUC unchanged.

Cyclosporine

Invitro experiments using human liver microsomes showed that rabeprazole inhibited cyclosporine metabolism with an IC of 50-62 micromol, i. e. at a concentration 50 times higher than the_maximum for healthy volunteers after 14 days of taking 20 mg of rabeprazole. 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 the simultaneous use of PPIs and methotrexate (especially in high doses) may lead to an increase in the concentration of methotrexate and / or its metabolite hydroxymethotrexate and increase the half-life.

However, no specific studies have been conducted on the drug interaction of methotrexate with PPIs.

Influence on the results of laboratory tests

The use of PPIs leads to a decrease in the acidity of gastric juice, which can lead to an increase in the content of chromogranin A (CgA) in the blood serum. Elevated CgA levels can lead to misinterpretation of laboratory results for the presence of neuroendocrine tumors. To avoid this effect, the use of Rabeloc®should be temporarily discontinued at least 14 days prior to the assessment of the blood pressure level; a repeat of the test should be considered if the baseline level remains high.

How to take, course of use and dosage

Rabelok tablets should not be chewed or crushed. Tablets should be swallowed whole. It was found that neither the time of day nor food intake affect the activity of rabeprazole sodium.

In case of acute gastric ulcer and anastomotic ulcer, it is recommended to take 20 mg orally once a day. Usually, recovery occurs after 6 weeks of therapy, but in some cases, the duration of treatment can be extended by another 6 weeks.

In case of acute duodenal ulcer disease, 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 extended by another 4 weeks.

When treating erosive gastroesophageal reflux disease (GERD) 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 extended by another 8 weeks.

For maintenance therapy of gastroesophageal reflux disease (GERD), it is recommended to take 20 mg orally once a day. The duration of treatment depends on the patient’s condition.

For non-erosive gastroesophageal reflux disease (GERD) without esophagitis, it is recommended to take 20 mg orally once a day.

If the symptoms persist after four weeks of treatment, additional testing of the patient should be performed.

After the symptoms are relieved, the drug should be taken orally once a day on demand to prevent their subsequent occurrence.

For the treatment of Zollinger-Allison 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 dosage of the drug is preferred.

Treatment should be continued as clinically necessary. In some patients with Zollinger-Allison syndrome, the duration of treatment with rabeprazole was up to one year.

For eradication of Helicobacter Pylori, it is recommended to take 20 mg orally 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

No dose adjustment is required in patients with renal insufficiency.

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 Rabeloc to patients with severe hepatic insufficiency.

Elderly patients

No dose adjustment is required.

Children

The safety and efficacy of rabeprazole sodium 20 mg for short-term (up to 8 weeks) treatment of GERD in children aged 12 years and older is confirmed by extrapolating the results of adequate and well-controlled studies supporting the effectiveness of rabeprazole sodium for adults and safety and pharmacokinetics studies for paediatric 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 treating GERD in children under 12 years of age has not been established. The safety and efficacy of rabeprazole sodium for other indications has not been established in paediatric patients.

Overdose

Symptoms. Information about overdose is minimal. Rabeprazole 60 mg twice daily and 160 mg once daily have been reported. Side effects were minimal and did not require medical intervention.

Treatment. The specific antidote is unknown. Rabeprazole binds well to plasma proteins and is therefore poorly excreted during dialysis.

In case of overdose, it is necessary to conduct symptomatic treatment.

Special instructions

The patient’s response to rabeprazole sodium therapy does not exclude the presence of malignancies in the stomach. Rabelok tablets should not be chewed or crushed. Tablets should be swallowed whole. It was found that neither the time of day nor food intake affect the activity of rabeprazole sodium.

In a special study in patients with mild or moderate hepatic impairment, there was no significant difference in the frequency of side effects of Rabeloc® It differs from that in healthy individuals selected by gender and age, but despite this, caution is recommended when first prescribing Rabeloc® to patients with severe hepatic impairment. The AUC of rabeprazole sodium in patients with severe hepatic impairment is approximately twice as high as in healthy patients.

In patients with impaired renal or hepatic function, adjust the dose of Rabeloc® not required.

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 therapy.

Serious adverse events included tetany, arrhythmia, and seizures. Most patients required treatment for hypomagnesaemia, including magnesium replacement and discontinuation of proton pump inhibitor therapy. In patients who will be receiving long-term treatment or who are taking proton pump inhibitors with medications such as digoxin or medications that may cause hypomagnesemia (such as diuretics), healthcare professionals should monitor their magnesium levels before starting treatment with proton pump inhibitors and during treatment.

Patients should not take other acid-reducing agents, such_{as H2} receptor blockers or proton pump inhibitors, at the same time as Rabeloc®.

Bone fractures

Observational studies suggest that therapy with proton pump inhibitors (PPIs) may increase the risk of osteoporosis-related hip, wrist, or spinal fractures. The risk of fractures was increased in patients who received high doses of PPIs for a long time (one year or more).

Concomitant use of rabeprazole with methotrexate

According to the literature, concomitant 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 the manifestation of methotrexate toxicity. If high doses of methotrexate are necessary, temporary discontinuation of PPI therapy may be considered.

Clostridium Difficile

PPI therapy may increase the risk of gastrointestinal infections, such as Clostridium Difficile.

Subacute cutaneous lupus erythematosus (PKKV)

There are reports of cases of PKKV in the treatment of PPIs. If skin lesions appear, especially in areas of the skin exposed to direct sunlight, and are accompanied by arthralgia, the patient should immediately seek medical attention, and the medical professional should decide to discontinue rabeprazole therapy.

The occurrence of PCV with previous PPIs may increase the risk of PCV with other PPIs. Glandular polyps of the bottom of the stomach

Long-term use of PPIs, including rabeprazole, appears to be associated with an increased risk of glandular polyps of the stomach floor. Most glandular polyps of the stomach floor are asymptomatic. Patients with large or ulcerated polyps may be at risk of gastrointestinal bleeding or small bowel obstruction.

The dosage and duration of PPI therapy for such patients should be minimal.

Influence on the ability to drive vehicles and mechanisms

Based on the specific pharmacodynamics of rabeprazole and its adverse effect profile, it is unlikely that Rabeloc®will be used in the treatment of patients with acute renal failure. it affects the ability to drive vehicles and mechanisms. However, if drowsiness occurs, these activities should be avoided.

Storage conditions

Store in a dry place protected from light at a temperature not exceeding 25 °C.

Keep out of reach of children!

Shelf

life is 2 years.

Active ingredient

Rabeprazole

Conditions of release from pharmacies

By prescription

Dosage form

Tablets