Rabeprazole-SZ - instructions for use, doses, side effects, contraindications

[pellet core: Rabeprazole sodium 10.00 mg, 20.00 mg, sugar grits (sucrose, molasses starch) - 71.47 mg, 142.94 mg, sodium carbonate - 1.65 mg, 3.30 mg, talc - 1.77 mg, 3.54 mg, titanium dioxide - 0.83 mg, 1.66 mg, hypromellose (hydroxymethylcellulose) - 14.75 mg, 29.50 mg;

pellet shell: hypromellose phthalate (hydroxypropyl methyl phthalate cellulose) - 15.93 mg, 31.86 mg, cetyl alcohol - 1.60 mg, 3.20 mg].

Excipients:

Capsules hard gelatin № 3 (dosage 10 mg):

body: titanium dioxide - 2.0%, gelatin - up to 100%;

lid: dye azorubin (dye karmazin) - 0.6619%, indigocarmine - 0.0286%, titanium dioxide - 0.6666%, gelatin - up to 100%.

Capsules hard gelatin № 1 (dosage of 20 mg):

body: titanium dioxide - 1.0%, iron oxide yellow - 0.192% gelatin - up to 100%;

lid: iron oxide black - 0.53%, iron oxide red - 0.93%, titanium dioxide - 0.3333%, iron oxide yellow - 0.20%, gelatin - up to 100%.

Description:

Hard gelatin capsules No. 3, white body with a lid of dark red color (for a dosage of 10 mg); Hard gelatin capsules No. 1, yellow body with brown lid (for a dosage of 20 mg).

The contents of the capsules are spherical pellets from almost white to white with a creamy or yellowish hue of color.

Pharmacotherapeutic group:glands of the stomach secretion-lowering agent - proton pump inhibitor

ATX: & nbsp

A.02.B.C Proton pump inhibitors

A.02.B.C.04 Rabeprazole

Pharmacodynamics:

Rabeprazole is a class of antisecretory substances, derivatives of benzimidazole. Suppresses the secretion of gastric juice by specific inhibition of H⁺/TO⁺-ATP-ase on the secretory surface of parietal cells of the stomach. It blocks the final stage of hydrochloric acid secretion, reducing the content of basal and stimulated secretion, regardless of the nature of the stimulus.

Possessing high lipophilicity easily penetrates into the parietal cells of the stomach, concentrates in them, providing a cytoprotective action and increasing the secretion of bicarbonate.

Antisecretory effect after oral administration of 20 mg of rabeprazole, occurs within 1 hour and reaches a maximum after 2-4 hours; inhibition of basal and stimulated food secretion of acid 23 hours after the first dose is 62 and 82%, respectively, and lasts up to 48 hours. At the termination of reception secretory activity is restored within 1-2 days.

During the first 2-8 weeks of therapy with rabeprazole, the concentration of gastrin in the blood plasma increases (which is a reflection of the inhibitory effect on the secretion of hydrochloric acid) and returns to baseline levels 1-2 weeks after it is discontinued.

Rabeprazole does not have anticholinergic properties, does not affect the central nervous system (CNS), cardiovascular and respiratory systems.

Against the background of taking rabeprazole, stable changes in the morphological structure of enterochromaxin-like cells, in the degree of gastritis, in the frequency of atrophic gastritis, intestinal metaplasia, or the spread of infection Helicobacter pylori not detected.

Pharmacokinetics:

Absorption

Rabeprazole is rapidly absorbed from the intestine, and its maximum plasma concentrations are reached about 3.5 hours after taking a dose of 20 mg. The change in the maximum concentrations in plasma (C_mOh) and the area values under the "concentration-time" curve (AUC) of rabeprazole are linear in the dose range of 10 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 is doubled in comparison with healthy volunteers, which indicates a decrease in the metabolism of the first passage, and the half-life of 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 food slows the absorption of rabeprazole by 4 hours or more, but neither C_max, 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 unchanged drug in the urine was found. About 90% of rabeprazole is excreted in the urine mainly in the form of two metabolites: the conjugate of mercapturic acid (M5) and the carboxylic acid (M6), and also in the form of two unknown metabolites detected during the toxicological analysis.

The rest of the accepted rabeprazole is excreted with feces.

The total excretion is 99.8%. These data indicate a slight excretion of metabolites of rabeprazole 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 <5 ml / min / 1.73 m²), the removal of rabeprazole is similar to that of healthy volunteers. AUC and FROM_mOhin these patients were approximately 35% lower than in healthy volunteers. On average, the half-life of rabeprazole was 0.82 h in healthy volunteers, 0.95 h in patients during hemodialysis and 3.6 h 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 in a dose of 20 mg once a day, although AUC doubled and C_mOh 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 taking rabeprazole 20 mg per day in elderly patients AUC was about twice as large, and C_mOh increased by 60% compared to young healthy volunteers. However, there were no signs of cumulation of rabeprazole.

CYP2C19 polymorphism

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

Indications:

- 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 (GERD) - adults and children with 12 years old 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 combination with appropriate antibiotic therapy for eradication Helicobacter pylori in patients with peptic ulcer.

Contraindications:

- Hypersensitivity to rabeprazole, substituted benzimidazolam or to the auxiliary components of the drug;

- sugarase / isomaltase deficiency, fructose intolerance, glucose-galactose insufficiency;

- pregnancy;

- the period of breastfeeding;

- children under 18, except for GERD (children under 12 years).

Carefully:

- Severe renal insufficiency;

- severe hepatic insufficiency.

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 on the use of the drug in the period of breastfeeding have not been conducted. At the same time rabeprazole is found in the milk of lactating rats, and therefore Rabeprazole can not be used in women during breastfeeding.

Dosing and Administration:

Capsules of the drug Rabeprazole-SZ should be swallowed whole. 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 (GERD) 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 (GERD) 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 (NERD) without esophagitis 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 on demand.

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 was 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 appropriate combinations of antibiotics. Duration of treatment is 7 days.

Patients with renal and hepatic insufficiency

Dose adjustments in patients with renal insufficiency are not required.

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

Care should be taken when administering rabeprazole-SZ to patients with severe hepatic impairment.

Elderly patients

Correction of the dose is not required.

Children

The safety and efficacy of rabeprazole 20 mg for short-term (up to 8 weeks) treatment of GERD in children aged 12 years or more is confirmed by extrapolating the results of adequate and well-controlled studies that support the efficacy of rabeprazole for adults and safety studies and pharmacokinetics for pediatric 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 for the treatment of GERD in children under the age of 12 years has not been established. The safety and efficacy of rabeprazole for use in other indications is not established for pediatric patients.

Side effects:

In the course of clinical studies, the following undesirable reactions with rabeprazole administration were noted: headache, dizziness, asthenia, abdominal pain, diarrhea, flatulence, dry mouth, rash.

Undesirable reactions are systematized in accordance with the WHO Classification:

Very often (> 1/10);

Often (> 1/100, <1/10);

Infrequently (> 1/1000, <1/100);

Rarely (> 1/10000, <1/1000);

Very rarely (<1/10000);

The frequency is unknown (can not be determined from the available data).

From the immune system: rarely - acute systemic allergic reactions (including facial edema, hypotension, dyspnea).

On the part of the blood and lymphatic system: rarely - thrombocytopenia, neutropenia, leukopenia.

From the side of metabolism and nutrition: rarely - anorexia; frequency is unknown - hyponatremia, hypomagnesemia.

From the nervous system: often - insomnia, headache, dizziness; infrequently - drowsiness, nervousness; rarely - depression; frequency is unknown - confusion.

From the side of the organ of vision: rarely - impaired vision.

From the side of the vessels: frequency unknown - peripheral edema.

From the respiratory system: often - cough, pharyngitis, rhinitis; infrequently - sinusitis, bronchitis.

From the digestive system: often - abdominal pain, diarrhea, flatulence, nausea, vomiting, constipation; infrequently - dyspepsia, belching, dry mouth; rarely - stomatitis, gastritis, taste disorder.

From the hepatobiliary system: rarely - hepatitis, jaundice, hepatic encephalopathy.

From the side of the kidneys and urinary tract: infrequently - infection urinary tract; rarely interstitial nephritis.

From the skin and subcutaneous tissues: rarely - bullous rashes, hives; very rarely - erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome.

From the musculoskeletal system: often - pain in the back; infrequently - myalgia, arthralgia, muscle cramp of legs, fracture of hip bone, wrist or spine.

From the side of the reproductive system: frequency unknown - gynecomastia.

From laboratory and instrumental research: rarely - increased activity of "liver" transaminases, weight gain.

Other: often - infection.

Overdose:

Symptoms

Data on intentional or accidental overdose are minimal.

Treatment

The specific antidote for rabeprazole 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:

Slows the excretion of certain drugs metabolized in the liver by microsomal oxidation (diazepam, phenytoin, indirect anticoagulants).

Joint use of rabeprazole with ketoconazole or itraconazole may lead to a significant decrease in the concentration of antifungal agents in the blood plasma.

It is not recommended to use proton pump inhibitors (PPIs) together with atanasavir together, since the effects of atanasavir are significantly reduced.

Rabeprazole inhibits the metabolism of cyclosporine.

With the simultaneous administration of PPI and methotrexate, one can assume an increase in the concentration of the latter and / or its metabolite, hydroxymototrexate, and an increase in the half-life.

With the simultaneous use of rabeprazole, amoxicillin and clarithromycin indicators AUC and C_mOh for clarithromycin and amoxicillin were similar when comparing combined therapy with monotherapy. Indicators AUC and C_mOh rabeprazole increased by 11% and 34%, respectively, a AUC and C_mOh 14-hydroxyclarithromycin (the active metabolite of clarithromycin) increased by 42% and 46%, respectively. This increase in indicators was not clinically significant.

The simultaneous use of rabeprazole and suspensions of antacids containing aluminum and / or magnesium hydroxide does not lead to a clinically significant interaction.

Special instructions:

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

Capsules of the drug Rabeprazole-SZ should be swallowed whole. It has been established that neither the time of day nor the intake of food affects the activity of rabeprazole.

In a special study in patients with mild or moderate liver function disorders, there was no significant difference in the frequency of adverse effects of the drug Rabeprazole-SZ from that of the healthy and selected for the sex and age, but in spite of this, it is advisable to use caution at the first appointment of the drug Rabeprazole- NW patients with severe impairment of liver function.

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

Hypomagnesemia

In the treatment of IPP for at least 3 months, 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 treatment of hypomagnesemia, which included the substitution of magnesium and the abolition of PPI therapy. In patients who will receive long-term treatment or who take PPI with drugs such as digoxin or drugs that can cause hypomagnesemia (eg, diuretics), health care providers should monitor the magnesium content before starting PPI treatment and during treatment.

Fractures

STI therapy may increase the risk of osteoporosis-related 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 (especially in high doses) may lead to an increase in the concentration of methotrexate and / or its metabolite, hydroxymototrexate, and increase the half-life, which may lead to toxicity of methotrexate. If it is necessary to use high doses of methotrexate, the possibility of temporary discontinuation of PPI therapy may be considered.

Infections, caused by Salmonella, Campylobacter and Clostridium difficile

STI therapy may lead to an increased risk of gastrointestinal infections, such as infections caused by Salmonella, Campylobacter and Clostridium difficile.

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 rabeprazole-SZ has an effect on the ability to drive vehicles and control mechanisms. However, in case of drowsiness, these activities should be avoided.

Form release / dosage:

Capsules enteric, 10 mg and 20 mg.

Packaging:

For 10 or 14 capsules in a contour mesh package.

For 30, 60 or 100 capsules in a can of polymer or a polymer bottle.

Each can or bottle, 2, 3, 6 contour cell packs of 10 capsules, 1, 2, 4 contour packs of 14 capsules together with the instructions for use are placed in a cardboard box.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003466

Date of registration:17.02.2016 / 21.07.2016

Expiration Date:17.02.2021

The owner of the registration certificate:NORTH STAR, CJSC NORTH STAR, CJSC Russia

Manufacturer: & nbsp

NORTH STAR, CJSC Russia

Representation: & nbspNORTH STAR CJSC NORTH STAR CJSC Russia

Information update date: & nbsp31.07.2016

Illustrated instructions

Instructions

Rabeprazole-SZ (Rabeprazol-SZ)