Pariet - instructions for use, dose, side effects, contraindications

Excipients (for a dosage of 10 mg): Mannitol (mannitol) - 26.0 mg, magnesium oxide 44.7 mg, hydroxypropylcellulose weakly substituted (giprolose) 13 mg, hydroxypropyl cellulose (giprolose) 4.0 mg, magnesium stearate 1.0 mg, ethylcellulose 0.7 mg, hypromellose phthalate 8.5 mg, diacetylated monoglyceride 0.85 mg, talc 0.80 mg, titanium dioxide (E171) 0.43 mg, iron oxide red (E172) 0.02 mg, carnauba wax - 0.0015 mg, food grade gray inks F6 (white shellac, iron oxide, black, ethanol dehydrated, 1-Butanol).

Description:

Pink biconvex tablets of rounded shape, covered with a coating, on one side marking with black ink "E241". The color of the tablet on the cross-section is from white to almost white.

Pharmacotherapeutic group:a means of reducing the secretion of the glands of the stomach - the proton pump inhibitor.

ATX: & nbsp

A.02.B.C Proton pump inhibitors

A.02.B.C.04 Rabeprazole

Pharmacodynamics:

Rabeprazole sodium belongs to the class of antisecretory substances, derivatives of benzimidazole. Rabeprazole sodium suppresses the secretion of gastric juice by specific inhibition H + / K + ATPase on the secretory surface of parietal cells of the stomach. H⁺/ K⁺ ATPase represents a protein complex, which 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 secretion of acid irrespective of the stimulus. Rabeprazole sodium does not possess anticholinergic properties.

Antisecretory action

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 the first dose of rabeprazole sodium is 69% and 82% respectively, and lasts up to 48 hours. This duration of pharmacodynamic action is much greater than the predicted half-life (approximately one hour). This effect can be explained by the long-term binding of the drug substance to H + / K + ATPase Parrietal 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 plasma

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

Effect on enterochromafin-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 enterochroma- phin-like cells, the degree of gastritis, the frequency of atrophic gastritis, intestinal metaplasia, or the spread of infection Helicobacter pylori were 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 in relation to the central nervous system, cardiovascular or respiratory systems are not currently detected. It was shown that rabeprazole sodium for oral administration at a dose of 20 mg for 2 weeks does not affect the function of the thyroid gland, carbohydrate metabolism, the level of rabeprazole for 4 hours or more,also on the level of cortisol, estrogens, testosterone, prolactin, glucagon, follicle-stimulating hormone (FSH), luteinizing hormone (LH), renin, aldosterone and growth hormone.

Pharmacokinetics:

Absorption.

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. Change in peak plasma concentrations (Сmах) and the values of the area under the curve "concentration-time" (AUC) rabeprazole are linear in the dose range from K) 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 half-life of 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 liver disease AUC increased by half compared to healthy volunteers, which indicates a decrease in metabolism of the first passage, and the half-life of plasma is increased by 2-3 times. No time drug intake during the knot, nor antacids affect the absorption of rabeprazole. Taking the drug with fatty food slows the absorption of rabeprazole by 4 hours or more, but neither Cmax, nor the degree of absorption is changed.

Distribution.

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

Metabolism and excretion.

In healthy people

After taking a single oral dose of 20 mg ¹⁴C-labeled rabeprazole sodium unchanged drug in the urine was found. About 90% of rabeprazole is excreted in the urine mainly in the form of two metabolites: conjugate mercapturic acid (M5) and carboxylic acid (M6), as well as in the form of two unknown metabolites detected during the toxicological analysis. The rest of the accepted rabeprazole sodium is excreted with feces. 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 <5ml / min / 1.73m '), removal of rabeprazole sodium is similar to that of healthy volunteers. AUC and C_max in these patients were approximately 35% lower than in healthy volunteers. The average half-life rabegrazole 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 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 once a day, although AUC doubled and Сmах 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 admission rabeprazole 20 mg per day in the elderly AUC was about twice as large, and Cmax increased by 60% compared to young healthy volunteers. However, the signs cumulation rabeprazole was not noted.

CYP2C19 polymorphism

In patients with delayed metabolism CYP2C19 after 7 days of taking rabeprazole in dose of 20 mg per day AUC increases in 1,9 times, and half-life in 1,6 times in comparison with the same parameters for "fast metabolizers", while Cmax increases by 40%.

Indications:

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

Contraindications:

hypersensitivity to rabeprazole, substituted benzimidazoles or to the auxiliary components of the drug;
pregnancy;
lactation period;
age to 18 years.

Carefully:Severe kidney failure.

Pregnancy and lactation:

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 in small quantities, the drug penetrates the placental barrier. Pariet® should not be used during pregnancy, except when the expected positive effect on the mother exceeds the possible harm to the fetus.

It is not known whether rabeprazole with breast milk. Appropriate studies in lactating women were not conducted. At the same time rabeprazole It is found in the milk of lactating rats, and therefore Pariet® can not be administered to lactating women.

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

Tablets of Pariet® preparation can not be chewed or grinded. Tablets should be swallowed whole. It is recommended to take the drug in the morning, before eating. It has been established that neither the time of day nor the intake of food does not influence the activity of rabeprazole sodium, but the recommended time of taking Pariet ® tablets promotes better adherence to the treatment regimen.

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.

Side effects:

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

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

HbudgetaryThe reactions are systematized relative to each of the organ systems using the following frequency classification:

Very frequent (> 1/10)

Frequent (> 1/100, <1/10)

Infrequent (> 1/1000, <1/100)

Rare (> 1/10000, <1/1000)

Very rare (<1/10000), including isolated cases.

Immune system disorders: rarely acute systemic allergic reactions;

Violations from the blood and lymphatic system: rarely - thrombocytopenia, neutropenia, leukopenia;

Disorders from the side of the substance and food rare-hypomagnesemia; observation of admission of PPIs may increase the risk of fractures (see section "Special instructions").

Disorders from the hepatobiliary system: increased activity of hepatic enzymes, rarely-genagit, jaundice, hepatic encephalopathy;

Disorders from the kidneys and urinary tract: very rarely - interstitial nephritis;

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

Disturbances from the musculoskeletal system: rarely - myalgia, arthralgia;

Disorders from the part of the reproductive system, very rarely - gynecomastia;

Changes in other laboratory parameters during the reception of rabsprazole sodium were not observed.

According to the data of aftermarket observations when taking proton pump inhibitors (PPI) it is possible to increase the risk of fractures (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 Pariet® is unknown. Rabeprazole binds well to plasma proteins, and therefore is 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 proton pump (PPI), is metabolized with the participation of the cytochrome P450 system (CYP450) in the liver. In studies in vitro microsomes of the human liver, it was shown that rabeprazole sodium is metabolized by isoenzymes CYP2C19 and CYP3A4.

Studies in healthy volunteers have shown that rabeprazole sodium ns has pharmacokinetic or clinically significant interactions with drugs that are metabolized by the cytochrome P450 - warfarin, phenytoin, theophylline and diazepam (regardless of whether patients are metabolized diazepam intensely or weakly).

A study of combination therapy with antibacterial drugs was conducted. In this four-sided cross-section study, 1 b of healthy volunteers participated, who took 20 mg of rabeprazole, 1000 mg of amoxicillin, 500 mg of clarithromycin, 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 ionotherapy. Indicators 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 in comparison with ionotherapy. This increase in exposure indices for rabeprazole and clarithromycin was not clinically significant.

Interactions due to inhibition secretion of gastric juice

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. With simultaneous reception with rabeprazole sodium absorption ketoconazole decreases by 30%, and absorption 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

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

Antacids

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

Food intake

In a clinical study, during the reception of rabeprazole sodium with depleted fat, no clinically significant interactions 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 human liver microsomes showed that rabeprazole inhibits the metabolism of cyclosporine with IC50 62 μmol, i.e., in a concentration 50 times greater than Cmax for healthy volunteers after 20 days of admission 20 mg rabeprazole. Degree of inhibition It is similar to that for omeprazole for equivalent concentrations.

Methotrexate

According to reports of adverse events, published pharmacokinetic studies and retrospective analysis data, it can be assumed that simultaneous reception of PPI and methotrexate (especially in high doses),can lead to increased concentrations methotrexate / or its metabolite, hydroxymetrexate, and increase half-life. Nevertheless, no special studies of the drug interaction of methotrexate with PPI have been conducted.

Special instructions:

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

Tablets of Pariet® preparation can not be chewed or grinded. Tablets should be swallowed whole. It has been established that neither the time of day nor the intake of food influence the activity of rabsprazole sodium.

In a special study in patients with mild or moderate impairment of liver function nc, a significant difference in the frequency of the side effects of Parieto® from that of the healthy individuals matched by sex and age was found, but despite this, it is advisable to use caution when first prescribing Pariet® patients with severe impairment of liver function. AUC Rabeprazole sodium in patients with severe impaired liver function is approximately twice as high as in healthy patients.

Patients with impaired renal or hepatic function adjust the dose of the drug Pariet® not required.

Hypomagnesemia

When treated with proton pump inhibitors for at least 3 months in 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 and convulsions. Most patients required the treatment of hypomagnesemia, including the replacement of magnesium and the abolition of therapy for the inhibitors of the purging pump. In patients who will receive long-term treatment or who take proton pump inhibitors with drugs such as dongoxin or drugs that can cause hypomagia (for example diuretics), health professionals should monitor the magnesium level before starting treatment with proton pump inhibitors and during treatment.

Patients should not take other drugs that reduce acidity, such as H2 receptor blockers or proton pump inhibitors, concomitantly with Parietet®.

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 of PPI for a long time (a year or more).

The simultaneous use of rabeprazole with methotrexate

According to the literature, simultaneous reception of PPI with methotrexate (primarily in high doses) may lead to an increase in the concentration of methotrexate and / or its metabolite tidroksimetotreksata and increase the period of excretion, which can lead to the manifestation of toxicity of methotrexate. If it is necessary to use high doses of methotrexate, the possibility of temporary discontinuation of PPI therapy may be considered.

Clostridium difficile

STI therapy may increase the risk of gastrointestinal infections, such as Clostridium difficile. Patients taking Pariet® for short-term symptomatic treatment of GERD and NERD (eg heartburn) without a prescription 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 non-intentional reduction body weight, anemia, bleeding in the gastrointestinal fact, dysphagia, pain when swallowing, constant vomiting or vomiting with blood and epigastric contents, cases of stomach ulcers or stomach operations and history, jaundice, etc. (including violations of the liver and kidneys).

Patients, long suffering from recurring symptoms of digestive disorders or heartburn, should be observed regularly by the doctor. Patients over 55 years of age who take OTC every day to relieve symptoms of heartburn and indigestion should inform their physician about this.

Patients should not take concomitantly with Parieto® other acid-reducing agents, such as blockers H₂receptors or proton pump inhibitors.

When using other medications, patients should consult a pharmacist or physician before starting therapy with Pariet® without prescription.

Patients should inform the doctor before using Pariet® without a prescription if they are given an endoscopic examination.

Prevent the use of Parieto® before performing a urea breath test.

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

Based on the peculiarities of pharmacodynamics of rabeprazole and its profile of undesirable effects, it is unlikely that Pariet® influences the ability to drive a car and work with machinery. However, if drowsiness occurs, these activities should be avoided

Form release / dosage:

Tablets coated with enteric coating 10 mg.

Packaging:For 7 or 14 tablets in a blister of 2 layers of aluminum. For 1 blister, along with instructions for medical use in a cardboard pack

Storage conditions:

At a temperature not higher than 25 ° C in a place inaccessible to children. Do not freeze

Shelf life:

2 years. Do not use after the expiration date

Terms of leave from pharmacies:On prescription

Registration number:П N011880 / 01

Date of registration:15.09.2011

The owner of the registration certificate:Johnson & Johnson, LLC Johnson & Johnson, LLC Russia

Manufacturer: & nbsp

CILAG, AG Switzerland

Information update date: & nbsp29.10.2014

Illustrated instructions

Instructions

Pariet® (Pariet®)