Rabeprazole capsules 10mg №28

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

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

Packaging

Enteric capsules, 10 mg, 14 capsules are placed in a blister packaging.
2 blister packs of 14 caps. placed in a carton box.

Mechanism of action

Pharmacotherapeutic 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, benzimidazole derivatives. Inhibits the secretion of gastric juice by specific inhibition of H + / K + -ATP-ase on the secretory surface of the parietal cells of the stomach. Blocks the final stage of secretion of hydrochloric acid, reducing the content of basal and stimulated secretion, regardless of the nature of the stimulus. Possessing high lipophilicity, it easily penetrates into the parietal cells of the stomach, concentrates in them, exerting a cytoprotective effect 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 food-stimulated acid secretion 23 hours after the first dose is 62 and 82%, respectively, and lasts up to 48 hours. When you stop taking secretory activity is restored within 1-2 days. During the first 2-8 weeks of treatment 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 canceled. Rabeprazole does not have anticholinergic properties, does not affect the central nervous system (CNS), cardiovascular and respiratory systems. In the presence of rabeprazole, steady changes in the morphological structure of enterochromine-like cells, in the severity of gastritis, in the frequency of atrophic gastritis, intestinal metaplasia, or the spread of Helicobacter pylori infection. 3

Pharmacokinetics

Absorption

Rabeprazole is rapidly absorbed from the intestine, and its maximum plasma concentrations are reached in about 3.5 hours after taking a dose of 20 mg. The change in the maximum plasma concentrations (Cmax) and the values ​​of the area under the concentration-time curve (AUC) of rabeprazole are linear in the dose range from 10 to 40 mg. Absolute bioavailability after oral administration of 20 mg (compared with intravenous administration) 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, AUC is doubled compared with healthy volunteers, which indicates a decrease in first-pass metabolism, and a half-life from plasma increased by 2 to 3 times. Neither the time of the drug intake during the day, nor antacids affect the absorption of rabeprazole. Taking the drug with fatty foods slows the absorption of rabeprazole for 4 hours or more, however, neither Cmax nor the degree of absorption does not change.

Distribution

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

Metabolism and excretion

Healthy people

After taking a single oral dose of 20 mg of a 14C-labeled rabeprazole, no unchanged drug was found in the urine. About 90% of rabeprazole is excreted in the urine mainly as two metabolites: a mercapturic acid conjugate (M5) and a carboxylic acid (M6), and also in the form of two unknown metabolites detected during toxicological analysis. The rest of the taken rabeprazole is excreted in the feces. The total elimination is 99.8%. These data indicate a small excretion of rabeprazole metabolites with bile. The main metabolite is thioether (M1). The only active metabolite is desmethyl (M3), but it was observed in a low concentration in only one study participant after taking 80 mg of rabeprazole.

End-stage renal disease

In patients with stable renal failure in the terminal stage, which require supporting hemodialysis (creatinine clearance <5 ml / min / 1.73 m2), the removal of rabeprazole is similar to that for healthy volunteers. AUC and Cmax in these patients were approximately 35% lower than in healthy volunteers. On average, the half-life of 4 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 in need of hemodialysis was approximately two times higher than in healthy volunteers.

Chronic compensated cirrhosis

Patients with chronic compensated cirrhosis of the liver tolerate rabeprazole in a dose of 20 mg once a day, although the AUC is doubled and Cmax increased by 50% compared with healthy volunteers of the corresponding sex.

In elderly patients, the elimination of rabeprazole is somewhat delayed. After 7 days of taking rabeprazole, 20 mg per day in elderly patients had approximately twice the AUC and Cmax increased by 60% compared with young healthy volunteers. However, signs of cumulation of rabeprazole were not observed.

CYP2C19 polymorphism

In patients with delayed CYP2C19 metabolism after 7 days of taking rabeprazole at a dose of 20 mg per day, the AUC increases 1.9 times, and the half-life 1.6 times compared with the same parameters in “fast metabolisers”, while Cmax increased by 40%.

• peptic ulcer of the stomach in the acute stage and ulcer of the anastomosis;
• peptic ulcer of the duodenum in the acute stage;
• erosive and ulcerative gastroesophageal reflux disease in adults and children from 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 the eradication of Helicobacter pylori in patients with peptic ulcer.

• hypersensitivity to rabeprazole, substituted benzimidazoles or auxiliary components of the drug;
• deficiency of sucrase / isomaltase, fructose intolerance, glucose-galactose deficiency;
• pregnancy;
• breastfeeding period;
• children under 18, with the exception of GERD (children under 12).

With care: severe renal failure; severe liver failure.

Pregnancy and Breastfeeding

There are no data on the safety of using rabeprazole during pregnancy.
Reproductive studies in rats and rabbits showed no signs of impaired fertility or fetal developmental defects due to rabeprazole; however, in rats in small quantities, the drug penetrates the placental barrier. Rabeprazole is contraindicated in pregnancy.
It is not known whether rabeprazole is excreted in breast milk.
Relevant studies on the use of the drug during the breastfeeding period were not conducted. However, rabeprazole was found in the milk of lactating rats, and therefore it cannot be used by women during breastfeeding.

The patient's response to rabeprazole therapy does not exclude the presence of malignant tumors in the stomach.
The capsules of Rabeprazole-SZ should be swallowed whole. It was established that neither the time of day nor food intake affect the activity of rabeprazole.
In a special study in patients with mild or moderate liver dysfunction, there was no significant difference in the frequency of side effects of Rabeprazole-SZ from that of healthy individuals matched by gender and age, but despite this, caution is advised when first prescribing Rabeprazole to patients with severe abnormal liver function.
Patients with impaired renal or hepatic function do not need to adjust the dose of Rabeprazole-SZ. AUC of rabeprazole in patients with severe hepatic impairment is approximately two times higher than in healthy patients.
Hypomagnesemia. In the treatment of PPI for at least 3 months, in rare cases, there have been cases of symptomatic or asymptomatic hypomagnesemia. In most cases, these messages were received one year after the treatment. Serious side effects were tetany, arrhythmia, and seizures.Most patients required treatment for hypomagnesemia, including Magnesium replacement and discontinuation of IPP therapy. In patients who will receive long-term treatment or who are taking an IPP with drugs such as Digoxin or capable of causing hypomagnesemia (such as diuretics), it is necessary to control the magnesium content before starting an IPP and during the treatment period.
Fractures. IPP therapy can 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 IPP for a long time (a year or more).
The simultaneous use of rabeprazole with Methotrexate . According to the literature, taking IPP with methotrexate at the same time (especially in high doses) can lead to an increase in the concentration of methotrexate and / or its metabolite hydroxymetotrexate and an increase in T1 / 2, which can lead to toxicity of methotrexate. If necessary, the use of high doses of methotrexate, may be considered the possibility of a temporary cessation of therapy with IPP.
Infections caused by Salmonella, Campylobacter and Clostridium difficile.
IPP therapy can increase the risk of gastrointestinal infections, such as infections caused by Salmonella, Campylobacter and Clostridium difficile.
Influence on ability to drive motor transport and control mechanisms. Based on the features of the pharmacodynamics of rabeprazole and its profile of undesirable effects, it is unlikely that Rabeprazole-SZ affects the ability to drive vehicles and control mechanisms. However, in the event of drowsiness, these activities should be avoided.

1 capsule contains:

Active substance:

rabeprazole pellets - 118 mg, 236 mg

in terms of rabeprazole sodium - 10 mg, 20 mg

[Pellet core: Rabeprazole sodium - 10.00 mg, 20.00 mg, sugar semolina (sucrose, starch syrup) - 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;

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

Excipients:

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

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

cap: dye azorubine (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: ferrous oxide black - 0.53%, ferric oxide red - 0.93%, titanium dioxide - 0.3333%, ferric oxide yellow - 0.20%, gelatin - up to 100%.

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

In case of peptic ulcer of the stomach in the acute stage and ulcer of the anastomosis, it is recommended to take orally 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 may be increased by another 6 weeks.

In case of peptic ulcer of the duodenum in the acute stage it is recommended to take orally 20 mg 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 increased by another 4 weeks. When treating erosive gastroesophageal reflux disease (GERD) or reflux esophagitis, it is recommended to take orally 10 mg or 20 mg 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 the maintenance therapy of gastroesophageal reflux disease (GERD), it is recommended to take orally 10 mg or 20 mg once a day. The duration of treatment depends on the condition of the patient.

For non-erosive gastroesophageal reflux disease (NERD) without esophagitis, it is recommended to take orally 10 mg or 20 mg once a day. If after four weeks of treatment the symptoms do not disappear, additional research should be carried out on the patient. After stopping the symptoms to prevent their subsequent occurrence, the drug should be taken orally at a dose of 10 mg once a day as required.

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 administered 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-Ellison syndrome, the duration of treatment with rabeprazole was up to one year.

For eradication of Helicobacter pylori, it is recommended to take orally 20 mg 2 times a day according to a specific regimen with appropriate combinations of antibiotics. The duration of treatment is 7 days.

Patients with renal and hepatic failure

Dose adjustment in patients with renal insufficiency is not required. In patients with mild to moderate hepatic insufficiency, the concentration of rabeprazole in the blood is usually higher than in healthy volunteers. In the appointment of the drug Rabeprazole-SZ patients with severe severity of liver failure, caution should be exercised.

Dose adjustment 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 and more is confirmed by extrapolating the results of adequate and well-controlled studies that support the effectiveness of rabeprazole for adults and safety and pharmacokinetics for children of children. The recommended dose for children aged 12 years or more is 20 mg 1 time per 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 has not been established for pediatric patients.

During clinical studies, the following adverse reactions were noted when taking rabeprazole: 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, Immune system: rarely - acute systemic allergic reactions (including swelling of the face, hypotension, shortness of breath).
From the side of blood and lymphatic system: rarely - thrombocytopenia, neutropenia, leukopenia.
Metabolism and nutrition: rarely - anorexia; frequency is unknown - hyponatremia, hypomagnesemia.
On the part of the nervous system: often - insomnia, headache, dizziness; infrequently - drowsiness, nervousness; rarely, depression; frequency unknown confusion.
On the part of the organ of vision: rarely - visual impairment.
On the part of the vessels: the frequency is unknown - peripheral edema.
On the part of the respiratory system: often - cough, pharyngitis, rhinitis; infrequently - sinusitis, bronchitis.
On the part of the digestive system: often - abdominal pain, diarrhea, flatulence, nausea, vomiting, constipation; infrequently - dyspepsia, belching, dry mouth; rarely - stomatitis, gastritis, taste disorder.
On the part of the hepatobiliary system: rarely - hepatitis, jaundice, hepatic encephalopathy.
On the part of the kidneys and urinary tract: infrequently - urinary tract infection; rarely interstitial nephritis.
From the skin and subcutaneous tissues: rarely - bullous rash, urticaria; very rarely - erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome.
On the part of the musculoskeletal system: often - back pain; infrequently - myalgia, arthralgia, leg muscle cramps, fractures of the hip, wrist or spine. <