Rabeprazol-SZ enteric-soluble capsules 20mg, 28pcs

Composition

1 capsule contains:

Active ingredient:

rabeprazole pellets-118 mg,236 mg

in terms of rabeprazole sodium-10 mg,20 mg

[pellet core:  Rabeprazole sodium – 10,00 mg of 20.00 mg, sugar nibs (sucrose, starch syrup) – 71,47 mg,142,94 mg, sodium carbonate is 1.65 mg, up to 3.30 mg, talc – of 1.77 mg of 3.54 mg, titanium dioxide – 0,83 mg of 1.66 mg, hypromellose (hydroxymethylcellulose) – 14,75 mg 29,50 mg;

shell pellets:  hypromellose phthalate (hydroxypropylmethylphthalate cellulose)- 15.93 mg,31.86 mg, cetyl alcohol-1.60 mg,3.20 mg].

Auxiliary substances:

Solid gelatin capsules No. 3 (dosage 10 mg):

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

cap:  dye azorubin (dye karmazin) – 0.6619%, indigo carmine-0.0286%, titanium dioxide-0.6666%, gelatin – up to 100%.

Solid gelatin capsules No. 1 (dosage 20 mg):

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

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

Pharmacological action

Pharmacotherapy group

Means of reducing the secretion of gastric glands-proton pump inhibitor

ATX code: [A02BC04]

Pharmacological properties

Pharmacodynamics

Rabeprazole belongs to the class of antisecretory substances derived from benzimidazole. It suppresses gastric juice secretion by specifically inhibiting H+ /K+ – ATPASE on the secretory surface of gastric parietal cells. Blocks the final stage of hydrochloric acid secretion, reducing the content of basal and stimulated secretion, regardless of the nature of the stimulus.

Having high lipophilicity, it easily penetrates the parietal cells of the stomach, concentrates in them, exerting a cytoprotective effect and increasing the secretion of bicarbonate. The antisecretory effect after oral use of 20 mg of rabeprazole occurs within 1 hour and reaches a maximum in 2-4 hours; inhibition of basal and food-stimulated acid secretion 23 hours after the first dose is 62 and 82%, respectively, and lasts up to 48 hours.

Upon discontinuation of the drug, secretory activity is restored within 1-2 days. During the first 2-8 weeks of rabeprazole therapy, the concentration of gastrin in blood plasma increases (reflecting the inhibitory effect on hydrochloric acid secretion) and returns to baseline levels 1-2 weeks after its withdrawal.

Rabeprazole does not have anticholinergic properties, does not affect the central nervous system (CNS), cardiovascular and respiratory systems. No stable changes in the morphological structure of enterochromafine-like cells, in the severity of gastritis, in the frequency of atrophic gastritis, intestinal metaplasia, or the spread of Helicobacter pylori infection were detected during rabeprazole use. 3

Pharmacokinetics

Absorption rate

Rabeprazole is rapidly absorbed from the intestine, and its maximum plasma concentrations are reached approximately 3.5 hours after taking a dose of 20 mg. Changes in the maximum plasma concentrations (Cmax) 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 the Cmax 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, no unchanged drug was found in the urine. About 90% of rabeprazole is excreted in the urine mainly in the form of two metabolites: a conjugate of mercapturic acid (M5) and carboxylic acid (M6), as well as in the form of two unknown metabolites detected during toxicological analysis.

The remainder of rabeprazole is excreted in the faeces. The total elimination rate is 99.8%. These data indicate a small excretion of rabeprazole 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 4 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 at a dose of 20 mg once a day, although the AUC is doubled and Cmax is 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 was approximately twice as high in elderly patients, and the Cmax was increased 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 Cmax increases by 40%.

Indications

• Acute gastric ulcer and anastomotic ulcer;
• Duodenal ulcer in the acute stage;
• Erosive and ulcerative gastroesophageal reflux disease (GERD) – adults and children from 12 years of age 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 antibacterial therapy for the 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. Rabeprazole-SZ should not be used during pregnancy.

It is not known whether rabeprazole is excreted in breast milk. Appropriate studies on the use of the drug during breastfeeding have not been conducted. However, rabeprazole is found in the milk of lactating rats, and therefore Rabeprazole-SZ should not be used in women during breastfeeding.

Contraindications

• Hypersensitivity to rabeprazole, substituted benzimidazoles or auxiliary components of the drug;
• sucrose/isomaltase deficiency, fructose intolerance, glucose-galactose insufficiency;
• pregnancy;
• breast-feeding;
• children under 18 years of age, with the exception of GERD (children under 12 years of age).

With caution:  

• severe renal insufficiency;

• severe hepatic insufficiency.

Side effects

In clinical trials, the following adverse reactions were reported when taking rabeprazole: headache, dizziness, asthenia, abdominal pain, diarrhea, flatulence, dry mouth, rash.

Adverse reactions are classified according to the WHO Classification:

Very often (> 1/10);>

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

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

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

Very rare (< 1/10000);

Frequency unknown (cannot be determined based on available data). Immune system disorders: rarely-acute systemic allergic reactions (including facial edema, hypotension, shortness of breath).

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

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

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

From the side of the organ of vision: rarely-visual impairment.

Vascular disorders: 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 disorders.

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

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

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

From the musculoskeletal system: often-back pain; infrequently-myalgia, arthralgia, leg muscle spasm, fracture of the hip, wrist or spine.

From the reproductive system: frequency unknown-gynecomastia. From laboratory and instrumental studies: rarely-increased activity of “hepatic” transaminases, increased body weight. Other: often-infections.

The interaction

slows down the elimination of certain drugs that are metabolized in the liver by microsomal oxidation (diazepam, phenytoin, indirect anticoagulants).

Concomitant use of rabeprazole with ketoconazole or itraconazole may significantly reduce the concentration of antifungal drugs in the blood plasma.

Concomitant use of proton pump inhibitors (PPIs) with atanazavir is not recommended, as the effects of atanazavir are significantly reduced. Rabeprazole inhibits cyclosporine metabolism.

Concomitant use of PPIs and methotrexate may suggest an increase in the concentration of the latter and/or its metabolite hydroxymetrexate and an increase in the elimination half – life.

When rabeprazole, amoxicillin, and clarithromycin were co-administered, the AUC and Cmax values for clarith|eomycin and amoxicillin were similar when compared with combination therapy and monotherapy. The AUC and Ctax of rabeprazole increased by 11% and 34%, respectively, and the AUC and Ctax of 14-hydroxyclarithromycin (the active metabolite of clarithromycin) increased by 42% and 46%, respectively. This increase was not considered clinically significant. Concomitant use of rabeprazole and antacid suspensions containing aluminum and / or magnesium hydroxide does not lead to a clinically significant interaction.

How to take, course of use and dosage

Rabeprazole-SZ capsules should be swallowed whole. It was found that neither the time of day nor food intake affect the activity of rabeprazole. In case of acute gastric ulcer and anastomotic ulcer, it is recommended to take 10 mg or 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. In some cases, the therapeutic effect occurs when taking 10 mg 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 10 mg or 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 10 mg or 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 10 mg or 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 relief of symptoms, to prevent their subsequent occurrence, the drug should be taken orally at a dose of 10 mg once a day on request.

For the treatment of Zollingeoa-Ellison syndrome and other conditions characterized by pathological hypersecoeia. 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-Ellison 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 appropriate combinations 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 volunteers.

Caution should be exercised when prescribing Rabeprazole-SZ to patients with severe hepatic insufficiency. Elderly patients No dose adjustment is required.

Children

The safety and efficacy of [eabeprazole 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 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 for the treatment of GERD in children under 12 years of age has not been established. The safety and efficacy of rabeprazole for other indications has not been established for paediatric patients.

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 during dialysis. In case of overdose, it is necessary to carry out symptomatic and supportive treatment.

Description

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

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

Special instructions

The patient’s response to rabeprazole therapy does not exclude the presence of malignancies in the stomach.

Rabeprazole-SZ capsules should be swallowed whole. It was found that neither the time of day nor food intake affect the activity of rabeprazole.

In a special study in patients with mild or moderate hepatic impairment, there was no significant difference in the frequency of side effects of Rabeprazole-SZ from those in healthy individuals selected by gender and age, but, despite this, caution is recommended when first prescribing Rabeprazole-SZ to patients with severe hepatic impairment.

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

Hypomagnesemia

Symptomatic or asymptomatic hypomagnesaemia has been reported in rare cases when PPIs have been treated for at least 3 months. 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 PPI therapy. In patients who will be receiving long-term treatment or who are taking PPIs with medications such as digoxin or medications that may cause hypomagnesemia (such as diuretics), healthcare professionals should monitor magnesium levels before starting PPIs treatment and during treatment. Fractures

PPI therapy may increase the risk of osteoporosis-related fractures in the hip, wrist, or spine. 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 required, temporary discontinuation of PPI therapy may be considered.

Infections caused by Salmonella, Campylobacter, and Clostridium difficile. PPI therapy may increase the risk of gastrointestinal infections, such as those caused by Salmonella, Campylobacter, and Clostridium difficile.

Influence on the ability to drive motor vehicles and manage mechanisms.

Based on the pharmacodynamic characteristics of rabeprazole and its undesirable effects profile, it is unlikely that Rabeprazole-SZ affects the ability to drive vehicles and manage mechanisms. However, if drowsiness occurs, these activities should be avoided.

Form of production

Enteric capsules of 10 mg and 20 mg. 10 or 14 capsules in a contour cell package. 30,60 or 100 capsules in a polymer jar or in a polymer bottle. Each jar or bottle,2,3,6 contour cell packs of 10 capsules,1,2,4 contour cell packs of 14 capsules together with the instructions for use are placed in a cardboard box.

Storage conditions

In a dry place, protected from light, at a temperature not exceeding 25 ” C. Keep out of reach of children.

Shelf

life is 3 years. Do not use after the expiration date indicated on the package.

Active ingredient

Rabeprazole

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

For adults by doctor’s prescription, Children by doctor’s prescription, Children over 12 years of age

Indications

Gastric and duodenal ulcers, GI infections caused by Helicobacter Pylori, Reflux Esophagitis