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

Composition:Each tablet, coated with enteric coating, 10 mg contains:
active substance: rabeprazole sodium 10 mg;
auxiliary substances: mannitol 48,505 mg, low-substituted giprolose 7.20 mg, magnesium oxide heavy 20.00 mg, hypromellose (5 cps) 1.50 mg, sodium lauryl sulfate 0.90 mg, talc 0.77 mg, magnesium stearate 1.125 mg.
Sheath: zein 2.45 mg, triethyl citrate 0.25 mg,
The shell is enteric-soluble: methacrylic acid and ethyl acrylate copolymer [1: 1] (methacrylic acid copolymer (type C)) 12.05 mg, triethyl citrate 1.20 mg, talc 0.65 mg.
Sheath: Opaprai pink O3B54475 2.70 mg (hypromellose 6cR 62.50%, titanium dioxide (E171) 28.70%, macrogol-400 6.25%, ferric oxide red oxide (E172) 2.55%).
Each tablet, coated with enteric coating, 20 mg contains:
active substance: rabeprazole sodium 20 mg;
auxiliary substances: mannitol 97.01 mg, low-substituted ginrolose 14.40 mg, magnesium oxide heavy 40.00 mg, hypromellose (5 cps) 3.00 mg, sodium lauryl sulfate 1.80 mg, talc 1.54 mg, magnesium stearate 2, 25 mg.
Sheath: zein 4.90 mg, triethyl citrate 0.49 mg.
The shell is enteric-soluble: methacrylic acid and ethyl acrylate copolymer [1: 1] (methacrylic acid copolymer (type C)) 19.28 mg, triethyl citrate 1.92 mg, talc 1.04 mg.
Casing: Fold yellow OY-52945 5.05 mg (hypromellose 5 cp 63.65%, titanium dioxide (E171) 28.55%, macrogol-400 6.30%, iron dye oxide yellow (E172) 1.50%) . Composition of black ink for inscription on a tablet 10 mg: shellac glaze (45%) 44.467%, iron dye black oxide (E172) 23.409%, isopropyl alcohol 26.882%, n-butanol 2.242%, propylene glycol 2.0%, ammonia solution concentrated 28% - 1.0%.
Composition of red ink for inscription on the tablet 20 mg: shellac glaze (45%) 59.0%, dye red charming (E129) 15.0%, n-butanol 7.0%, ethanol denatured 6.0%, titanium dioxide (E171) 5.0%, propylene glycol 4.0%, isopropyl alcohol 3.0%,ammonia solution concentrated 28% - 1.0%.

Description:Intestine-soluble film coated tablets, 10 mg

Round, biconvex tablets, covered with a coat from pink to brownish pink with a black marking "RB10" on one side. On the cross section, the nucleus is almost white.
Intestine-coated coating tablets, 20 mg

Round, biconvex tablets, coated with a cover from light yellow to yellow with a red marking "RB20" on one side. On the cross section, the nucleus is almost white.

Pharmacotherapeutic group:The iron of the stomach secretion is a reducing agent - a proton pump inhibitor.

ATX: & nbsp

A.02.B.C Proton pump inhibitors

A.02.B.C.04 Rabeprazole

Pharmacodynamics:Mechanism of action. Rabeprazole belongs to the class of antisecretory compounds, which are chemically substituted benzimidazoles. The drug inhibits the activity of the enzyme H + / K + ATPase ("proton pump"), thereby blocking the final stage of the synthesis of hydrochloric acid. This effect is dose-dependent and leads to inhibition of both basal and stimulated secretion of hydrochloric acid regardless of the stimulus. As a weak foundation rabeprazole in any doses is rapidly absorbed and concentrated in the acidic environment of parietal cells. Antisecretory activity. After ingestion of 20 mg of rabeprazole, the antisecretory effect occurs within one hour. Inhibition of basal and stimulated secretion of hydrochloric acid 23 hours after the first dose of rabeprazole sodium is 62 and 82%, respectively, and lasts up to 48 hours. This duration of pharmacokinetic action is much higher than the predicted half-life (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 magnitude of the inhibitory effect of rabeprazole sodium on acid secretion reaches a plateau after three days of taking rabeprazole sodium. Upon discontinuation, the secretory activity is restored within 142 days. Effect on the concentration of gastrin in serum. At the beginning of rabeprazole therapy, the concentration of gastrin in the serum increases, which is a reflection of the inhibitory effect on the secretion of hydrochloric acid. The concentration of gastrin returns to baseline usually within 1 ~ 2 weeks after discontinuation of treatment.
Influence on enterochromafin-like cells.
The study of biopsies of the bottom and antrum of the stomach in more than 500 patients who received rabeprazole sodium or a comparator for up to 8 weeks, showed no changes in the morphological structure of enterochromachine-like (ECL) cells, the degree of gastritis, the frequency of atrophic gastritis, intestinal metaplasia, or the prevalence of infection with Nonlicobacter pouli. In a study involving more than 400 patients who received rabeprazole at a dose of 10 mg / day or 20 mg / day, up to 1 year, the incidence of hyperplasia was low and comparable to that of patients who received omeprazole in a dose of 20 mg / day. No case of adenomatous changes or carcinoid tumors observed in rats was recorded.
Other effects.
Currently, there is no evidence that rabeprazole causes systemic effects from the central nervous system (CNS), cardiovascular and respiratory systems. When administered orally at a dose of 20 mg for 2 weeks rabeprazole did not affect the function of the thyroid gland, the metabolism of carbohydrates, as well as the concentration in the blood of parathyroid hormone, cortisol, estrogens, testosterone,prolactin, secretin, glucagon, follicle-stimulating hormone, luteinizing hormone, renin, aldosterone and growth hormone.

Pharmacokinetics:Absorption is high, the time to reach the maximum concentration (Tcmax) is 3.5 hours. Changes in the maximum concentration (Cmax) and area values under the concentration-time curve (AUC) are linear in the dose range of 10-40 mg. Metabolised in the liver with the participation of isoenzymes CYP2C9 and CYP3A. Bioavailability - 52%, does not increase with multiple admission. The half-life (T1 / 2) is 0.7-1.5 hours, the total clearance is 3.8 ml / min / kg. In patients with hepatic insufficiency AUC increases by 2 times, T1 / 2 increases 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 the absorption of the drug for 4 hours or more, but neither Cmax nor the degree of absorption does not change. The connection with plasma proteins is 97%. It is excreted by the kidneys (90%) in the form of two metabolites: a conjugate of mercapturic acid (M5) and a carboxylic acid (M6); through the intestine - 10%. Differences in pharmacokinetic parameters were not observed depending on sex.

Pharmacokinetics in special clinical cases.

Renal insufficiency
In patients with stable end-stage renal failure who require maintenance hemodialysis (creatinine clearance <5 mL / min / 1.73 m2), the removal of rabeprazole is similar to that of healthy volunteers. AUC and Cmax in these patients were approximately 35% lower than in healthy volunteers. On average, T1 / 2 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 disease requiring hemodialysis was approximately twice that of healthy volunteers.

Liver failure

Patients with chronic compensated cirrhosis are well tolerated rabeprazole in a dose of 20 mg once a day, although AUS is doubled and Cmax is increased by 50% compared to healthy volunteers.

Elderly patients

In elderly patients, the elimination of rabeprazole is somewhat slowed down. After 7 days of taking rabeprazole in a dose of 20 mg once a day, the AUC was approximately twice as high in elderly people, and Cmax was increased by 60% compared to young healthy volunteers; There were no signs of cumulation of rabeprazole.

CYP2S19 polymorphism

In patients with delayed metabolism of CUR2C19 after 7 days of taking rabeprazole at a dose of 20 mg per day, the AUC increases 1.9-fold, and the half-life is 1.6-fold, compared to the same parameters for "fast metabolizers," while Смах increases by 40%.

Indications:Indications for use

- Stomach ulcer in the stage of exacerbation and ulcer of anastomosis;

- peptic ulcer of duodenum in the stage of exacerbation;

- erosive and ulcerative gastroesophageal reflux disease or reflux esophagitis;

- maintenance therapy of gastroesophageal reflux disease;

- non-erosive gastroesophageal reflux disease;

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

In the combination therapy:

- eradication of Helicobacter pylori in patients with peptic ulcer of stomach and duodenum or chronic gastritis.

Contraindications:

Hypersensitivity to rabeprazole, substituted benzimidazoles or to the auxiliary components of the drug; pregnancy; the period of breastfeeding (lactation); children under 12 years.

Carefully:

Severe renal insufficiency, severe hepatic insufficiency, children's age.

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. Rabeprazole should not be used during pregnancy. 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, so the drug can not be used during breastfeeding.

Dosing and Administration:

Tablets are taken internally as a whole, without chewing or grinding. It has been established that neither the time of day nor the intake of food affects the activity of rabeprazole.

With peptic ulcer in the stage of exacerbation and ulcer of anastomosis it is recommended to take inside 10 mg or 20 mg once a day. Usually, the cure comes after 6 weeks of therapy, but in some cases the duration of treatment can be increased by another 6 weeks.

With duodenal ulcer in the acute stage it is recommended to take inside 20 mg once a day. In some cases, the therapeutic effect occurs when taking 10 mg once a day. 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 or reflux esophagitis it is recommended to take inside 10 mg or 20 mg once a day. 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 of gastroesophageal reflux disease it is recommended to take inside 10 mg or 20 mg once a day. The duration of treatment depends on the patient's condition.

With non-erosive gastroesophageal reflux disease it is recommended to take inside 10 mg or 20 mg once a day.

If after four weeks of treatment the symptoms do not disappear, an additional study of the patient should be carried out. After relief of symptoms to prevent their subsequent occurrence, the drug should be taken orally at a dose of 10 mg once a day.

For the treatment of Zollinger-Ellison 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 given 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 clinical need arises. In some patients with Zollinger-Ellison syndrome, the duration of treatment with rabeprazole can be up to one year.

For eradication Helicobacter pylori it is recommended to take inside 20 mg twice a day according to a certain scheme with the appropriate combination of antibiotics. Duration of treatment is 7 days.

Patients with renal and hepatic insufficiency.

Correction of a dose to patients with renal insufficiency is not required.

In patients with mild and moderate hepatic insufficiency, the concentration of rabeprazole in the blood is usually higher than in healthy patients.

Care should be taken when administering Pazo® to patients with severe hepatic impairment.

Elderly patients.

Correction of the dose is not required.

Children.

The safety and efficacy of rabeprazole in children aged 12 years and older is established for short-term (up to 8 weeks) treatment of GERD. The recommended dose for children aged 12 years and older is 20 mg once a day for up to 8 weeks. The safety and efficacy of rabeprazole for use in other indications is not established for pediatric patients.

Side effects:

Rabeprazole is usually well tolerated by patients. Side effects are generally mild or moderate and of a transient nature.

The incidence of side effects is described in accordance with the following gradation: very often (> 1/10); often (1/10 - 1/100); infrequently (1/100 - 1/1000); rarely (1/1000 - 1/10000); very rarely (<1/10000).

Impaired nervous system: infrequently - headache, dizziness.

Disorders from the gastrointestinal tract: often - constipation, diarrhea, abdominal pain, dryness of the oral mucosa, flatulence; rarely - hepatitis, jaundice; in patients with cirrhosis of the liver - hepatic encephalopathy.

Disturbances from the skin and subcutaneous tissues: rarely - hives, bullous eruptions,Lyell's syndrome (toxic epidermal necrolysis), Stevens-Johnson syndrome (severe erythema multiforme, characterized by the appearance of spots and blisters on the skin and mucous membranes amid high fever and joint pain).

Disturbances from the musculoskeletal and connective tissue: rarely - myalgia, arthralgia.

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

Laboratory and instrumental data: rarely - thrombocytopenia, neutropenia, leukopenia, leukocytosis, increased activity of "liver" enzymes (transaminase), hypomagnesemia.

Possible increased risk of bone fractures {cm. section "Special instructions").

Overdose:

Symptoms. Data on intentional or accidental overdose are minimal. It was reported that the drug was taken in a dose of 60 mg 2 times a day or 160 mg once, while the side effects were minimal and reversible and did not require medical intervention.

Treatment. The specific antidote for Pazo® is unknown. Rabeprazole binds well to plasma proteins, so it is poorly excreted in dialysis.In case of an overdose, symptomatic and supportive treatment should be performed.

Interaction:

In studies in vitro on human liver microsomes it was shown that rabeprazole metabolized in the liver by isoenzymes CYP2C19 and CYP3A4.

Rabeprazole does not enter into clinically significant interactions with amoxicillin and other drugs metabolized by isoenzymes of the cytochrome P450 system in the liver: warfarin, phenytoin, theophylline, and diazepam.

Due to rabeprazole causes a pronounced and prolonged decline in the production of hydrochloric acid, there was an interaction with simultaneous reception with drugs, the absorption of which depends on the acidity of the contents of the stomach. In healthy volunteers, the use of rabeprazole caused a decrease in the concentration of ketoconazole in the blood plasma by 30% and an increase in the minimum digoxin concentration by 22%. With the simultaneous administration of rabeprazole with ketoconazole or digoxin, their doses should be adjusted.

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.Thus, concurrent administration of atazanavir with proton pump inhibitors is not recommended, including rabeprazole.

Concentrations of rabeprazole and the active metabolite of clarithromycin in blood plasma with simultaneous admission are increased by 24% and 50%, respectively. This effect is used in eradication Helicobacter pylori.

The simultaneous administration of rabeprazole and methotrexate may lead to an increase in the concentration of methotrexate and its metabolite hydroxymototrexate and increase the time of their elimination.

There was no interaction of rabeprazole with liquid antacids.

There was no clinically significant interaction of rabeprazole with food.

Special instructions:

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

Before and after treatment, endoscopic control is necessary to exclude malignant neoplasm, since the treatment can mask the symptoms and delay proper diagnosis.

It is advisable to take care when administering Pazo® for the first time to patients with severe impairment of liver function.

Patients with impaired renal or hepatic function are not required to adjust the dose of Pazo®. AUC Rabeprazole sodium in patients with severe impaired liver function is approximately twice as high as in healthy patients.

The drug does not affect the function of the thyroid gland, the metabolism of carbohydrates, the concentration in the blood of parathyroid hormone, cortisol, estrogen, testosterone, prolactin, cholecystokinin, secretin, glucagon, follicle stimulating hormone, luteinizing hormone, renin, aldosterone and somatotropic hormone.

According to observational studies, proton pump inhibitor therapy may lead to an increased risk of osteoporotic fractures of the hip, wrist, spine. The risk of fractures was increased in patients who received high doses of proton pump inhibitors for a year or more.

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 the Paso® drug affects the ability to drive vehicles and perform other activities requiring attention and speed of psychomotor reactions.However, if drowsiness occurs, dizziness should be avoided.

Form release / dosage:

Tablets coated with enteric-coated shell, 10 mg and 20 mg.

Packaging:

For 15 or 30 tablets in high-density polyethylene cans with a screw neck, equipped with a membrane for the control of the first opening, sealed with plastic screw caps with a gasket and inserting a bag with a desiccant (silica gel) and a polyester wool tampon. Each bank, together with instructions for use, is placed in a cardboard box.

For 15 tablets in a blister of (PVC / AL / PA) foil / aluminum foil. For 1 or 2 blisters together with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C. Keep out of the reach of children!

Shelf life:

2 years (in banks), 3 years (in blisters). Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002666

Date of registration:20.10.2014

The owner of the registration certificate:Dr. Reddy's Laboratories Ltd.Dr. Reddy's Laboratories Ltd. India

Manufacturer: & nbsp

DR. REDDY`S LABORATORIES, LTD. India

Representation: & nbspDR REDDY'S LABORATORIS LTD. DR REDDY'S LABORATORIS LTD. India

Information update date: & nbsp20.10.2014

Illustrated instructions

Instructions

Russo® (Razo®)