Rabeprazole | 20 mg tablets, 14 pcs.

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SKU
BID462077
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Latin name

Pariet
Latin name

Pariet

Release form

Enteric coated tablets.

Packing

14 pcs

Pharmacological action

Pariet - antiulcer.

Pharmacodynamics

Mechanism of action

Rabeprazole sodium belongs to the class of antisecretory substances derived from benzimidazole. Rabeprazole sodium inhibits the secretion of gastric juice by specific inhibition of H + / K + -ATPase on the secretory surface of parietal cells of the stomach. 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 the suppression of both basal and stimulated secretion of acid, regardless of the stimulus. Rabeprazole sodium does not have anticholinergic properties.

Antisecretory effect of

After oral administration of 20 mg of rabeprazole sodium, the antisecretory effect develops within an hour. Inhibition of basal and stimulated acid secretion 23 hours after taking the first dose of rabeprazole sodium is 69 and 82%, respectively, and lasts up to 48 hours. This duration of pharmacodynamic action far exceeds the predicted T1 / 2 (approximately 1 hour). This effect can be explained by the prolonged binding of the drug substance to the H + / K + -ATPase of parietal cells of the stomach. The value of the inhibitory effect of rabeprazole sodium on acid secretion reaches a plateau after three days of taking rabeprazole sodium. When you stop taking it, secretory activity is restored within 1-2 days.

Effect on plasma gastrin level

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

Effect on enterochromaffin-like

cells When examining gastric biopsy specimens The concentration of gastrin returned to its original level usually within 1-2 weeks after discontinuation of treatment.

Effect on enterochromaffin-like

cells When examining gastric biopsy specimens The concentration of gastrin returned to its original level usually within 1-2 weeks after discontinuation of treatment.

Effect on enterochromaffin-like

cells When examining gastric biopsy specimens500 patients who received rabeprazole sodium or a comparison drug for up to 8 weeks, persistent 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 found in a person from the antrum and the bottom of the stomach.

In a study of more than 400 patients receiving rabeprazole sodium (10 or 20 mg / day) for up to 1 year, the incidence of hyperplasia was low and comparable to that of omeprazole (20 mg / kg). Not a single case of adenomatous changes or carcinoid tumors observed in rats was recorded.

Other effects of

Systemic effects of rabeprazole sodium in relation to the central nervous system, cardiovascular or respiratory systems are not currently detected. It was shown that rabeprazole sodium when taken orally at a dose of 20 mg for 2 weeks does not affect thyroid function, carbohydrate metabolism, the level of parathyroid hormone in the blood, as well as the level of cortisol, estrogen, testosterone, prolactin, glucagon, FSH, LH, renin, aldosterone and STH.

Pharmacokinetics

Absorption of

Rabeprazole is rapidly absorbed from the intestine, and plasma Cmax is reached approximately 3.5 hours after administration at a dose of 20 mg. The change in C max and AUC values ​​of rabeprazole are linear in the dose range from 10 to 40 mg. The absolute bioavailability after oral administration of 20 mg (compared with iv) is about 52%. In addition, bioavailability does not change with multiple doses of rabeprazole. In healthy volunteers, plasma T1 / 2 is about 1 hour (0.7–1.5 hours), and the total clearance is 3.8 ml / min / kg. In patients with chronic liver damage, AUC is doubled compared with those in healthy volunteers, which indicates a decrease in the metabolism of the first passage, and T1 / 2 from 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 foods slows down the absorption of rabeprazole for 4 hours or more, however, neither Cmax nor the degree of absorption change.

Distribution of

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

Metabolism and excretion

In healthy people. After a single dose of 20 mg of labeled 14C rabeprazole sodium, unchanged drug was not found in the urine. About 90% of rabeprazole is excreted in the urine, mainly in the form of two metabolites: conjugate of mercapturic acid (M5) and carboxylic acid (M6), as well as in the form of two unknown metabolites identified during toxicological analysis. The rest of the taken rabeprazole sodium is excreted in the feces. The total elimination is 99.8%. These data indicate a small excretion of metabolites of rabeprazole sodium with bile. The main metabolite is thioether (M1). The only active metabolite is desmethyl (M3), however, it was observed in low concentration in only one study participant after taking 80 mg of rabeprazole.

End-stage renal failure. In patients with stable end-stage renal failure who require maintenance hemodialysis (Clcreatinin <5 ml / min / 1.73 m2), excretion of rabeprazole sodium is similar to that in healthy volunteers. AUC and Cmax in these patients were approximately 35% lower than in healthy volunteers. The average T1 / 2 of 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 diseases requiring hemodialysis was approximately 2 times higher than 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 Cmax is increased by 50% compared with healthy volunteers of the corresponding sex.

Elderly patients. In elderly patients, elimination of rabeprazole is somewhat delayed. After 7 days of taking rabeprazole at 20 mg / day in the elderly, the AUC was about twice that and Cmax increased by 60% compared with young healthy volunteers. However, no signs of cumulation of rabeprazole were noted.

CYP2C19 polymorphism. In patients with a slowed metabolism of CYP2C19, after 7 days of taking rabeprazole at a dose of 20 mg / day, AUC increases by 1.9 times, and T1 / 2 - by 1.6 times compared with the same parameters in fast metabolizers, while Cmax increases by 40%.

Indications

Peptic ulcer in step exacerbation and ulcer anastomosis

duodenal ulcer in the acute stage

erosive GERD or reflux esophagitis

maintenance therapy of gastroesophageal reflux disease

non-erosive gastroesophageal reflux disease

Zollinger-Ellison syndrome and other conditions characterized by pathological hypersecretion of

in combination with appropriate antibacterial therapy for eradication of Helicob acter pylori in patients with peptic ulcer.

Contraindications

Hypersensitivity to rabeprazole, substituted benzimidazoles or to auxiliary components of the

preparation pregnancy and lactation period

children under 12 years of age.

Caution: apply in patients with severe renal failure of a severe degree, in childhood.

Composition

1 tablet contains:

Active substances: rabeprazole sodium 20 mg, which corresponds to the content of rabeprazole 18.85 mg.

Excipients: mannitol (mannitol) - 40.0 mg, magnesium oxide - 63.0 mg, slightly substituted hydroxypropyl cellulose (hyprolose) - 19.5 mg, hydroxypropyl cellulose (hyprolose) - 3.0 mg, magnesium stearate - 1.5 mg ethyl cellulose - 1.0 mg, hypromellose phthalate - 12.0 mg, diacetylated monoglyceride - 1.2 mg, talc - 1.13 mg, titanium dioxide (E171) - 0.6 mg, yellow iron oxide - 0.07 mg , carnauba wax - 0.025 mg, edible red ink A1 (white shellac, iron oxide red, carnauba wax, glyceric acid ester, ethanol dehydrated, 1-butanol).

Dosage and administration

Pariet tablets should be swallowed whole without chewing or crushing. It was found that neither the time of day nor the meal affects the activity of rabeprazole sodium.

For gastric ulcer in the acute stage and anastomosis ulcer

It is recommended to take 20 mg orally once a day. Usually, cure occurs after 6 weeks of therapy, but in some cases, the duration of treatment can be increased by another 6 weeks.

In case of peptic ulcer in the exacerbation stage

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 increased by another 4 weeks.

In the treatment of 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 increased by another 8 weeks.

With maintenance therapy for gastroesophageal reflux disease (GERD)

It is recommended that you take orally 20 mg once a day. The duration of treatment depends on the patient's condition.

For non-erosive gastroesophageal reflux disease (NERD) without esophagitis

It is recommended to be taken orally at 20 mg once a day.

If the symptoms do not disappear after four weeks of treatment, an additional examination of the patient should be performed.

After stopping the symptoms, to prevent their subsequent occurrence, the drug should be taken orally once a day upon request.

For the treatment of Zollinger-Alison 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 with a single dose or 60 mg twice a day. For some patients, fractional dosing of the drug is preferred. Treatment should continue as needed. In some patients with Zollinger-Alison syndrome, the duration of treatment with rabeprazole was up to one year.

For the eradication of Helicobacter pylori

It is recommended to be taken orally at 20 mg 2 times a day according to a specific scheme with the appropriate combination of antibiotics. The duration of treatment is 7 days.

Patients with Renal and Hepatic Insufficiency

Dose adjustment is not required for patients with renal failure.

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 the drug Pariet to patients with a severe degree of liver failure.

Elderly patients

Dose adjustment not required.

Children

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

Safety and effectiveness of rabeprazole sodium for the treatment of GERD in children under the age of 12 have not been established.

Safety and effectiveness of rabeprazole sodium for other indications have not been established in pediatric patients.

Side effects

Immune system disorders: rarely - acute systemic allergic reactions.

Disorders from the blood and lymphatic system: rarely - thrombocytopenia, neutropenia, leukopenia.

Disorders from metabolism and nutrition: rarely - hypomagnesemia.

Disorders from the hepatobiliary system: increased activity of hepatic enzymes, rarely hepatitis, jaundice, hepatic encephalopathy.

Disorders of the kidneys and urinary tract: very rarely - interstitial nephritis.

Disorders from the skin and subcutaneous tissues: rarely - bullous rashes, urticaria, very rarely - erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome.

Disorders from the musculoskeletal system: rarely - myalgia, arthralgia.

Reproductive system disorders: very rarely - gynecomastia.

Drug Interaction

Cytochrome P450

system Rabeprazole sodium, like other proton pump inhibitors (PPIs), is metabolized by the involvement of the cytochrome P450 (CYP450) system in the liver. In vitro studies on human liver microsomes have shown that rabeprazole sodium is metabolized by the CYP2C19 and CYP3A4 isoenzymes. Research on healthy volunteers has shown that rabeprazole sodium does not have pharmacokinetic or clinically relevant interactions with medicinal products that are metabolized by the cytochrome P450 system - warfarin, phenytoin, theophylline, and diazepam (whether or not patients metabolize diazepam intensely or weakly). A study of combination therapy with antibacterial drugs was conducted. This four-way cross-sectional 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 (CANCER: rabeprazole, amoxicillin, clarithromycin). The AUC and Cmax rates for clarithromycin and amoxicillin were similar when compared to combination therapy with monotherapy. AUC and Cmax for rabeprazole increased by 11% and 34%, respectively, and for 14-hydroxy-clarithromycin (the active metabolite of clarithromycin), AUC and Cmax increased by 42% and 46%, respectively, for combination therapy compared to monotherapy. This increase in exposure for rabeprazole and clarithromycin was not considered clinically relevant.

Interactions due to inhibition of gastric juice secretion

Rabeprazole sodium exerts a steady and prolonged suppression of gastric juice secretion. Thus, interactions with substances for which absorption is pH dependent may occur. When co-administered with rabeprazole sodium, ketoconazole absorption is reduced by 30% and digoxin absorption is increased by 22%. Therefore, Some patients should be monitored to resolve the need for dose adjustments while receiving rabeprazole sodium with ketoconazole, digoxin or other drugs for which absorption is pH dependent.

Atazanavir

A significant reduction in atazanavir exposure was observed with concomitant administration of atazanavir 300 mg / ritonavir 100 mg with omeprazole (40 mg once daily) or with atazanavir 400 mg with lansoprazole (60 mg once daily). Atazanavir absorption is pH dependent. Although co-administration with rabeprazole has not been studied, similar results are expected for other PPIs. Therefore, concomitant administration of atazanavir with proton pump inhibitors, including rabeprazole, is not recommended.

Antacids

In clinical studies, antacids were co-administered with rabeprazole sodium. No clinically relevant interactions of rabeprazole sodium with aluminum hydroxide gel or magnesium hydroxide were observed.

Food intake

In a clinical trial, no clinically relevant interactions were observed during the administration of rabeprazole sodium with low fat foods. Taking rabeprazole sodium at the same time as fat-enriched foods can delay 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 showed that rabeprazole inhibited cyclosporine metabolism with IC50 of 62 μmol, ie at a concentration 50 times the Cmax for healthy volunteers after 20 days of taking 20 mg of rabeprazole. The degree of inhibition is similar to that for omeprazole for equivalent concentrations.

Methotrexate

According to reports of undesirable effects, published pharmacokinetic studies and retrospective data, it can be assumed that concomitant administration of PPI and methotrexate (primarily in high doses) may increase the concentration of methotrexol or methotrexol / 2. However, no specific studies of the drug interaction of methotrexate with STIs have been performed.



overdose Symptoms: data on intentional or accidental overdose are minimal. No cases of severe overdose with rabeprazole were noted.

Treatment: The specific antidote for the drug Pariet is unknown. Rabeprazole binds well to plasma proteins and is therefore poorly excreted in dialysis. In case of overdose, symptomatic and supportive treatment should be performed.

Storage conditions

Store at a temperature not exceeding 25 РC and do not freeze.

Expiration

2 years.

Deystvuyuschee substances

Rabeprazole

dosage form

dosage form

tablets

Bush Pharmaceuticals, Japan

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