Description
Latin name
Razo
Release form
tablets
Packaging
30 pcs
Pharmacological action of
Pharmacodynamics of
Mechanism of action of
Rabeprazole belongs to the class of antisecretory agents which are chemically substituted by benzimidazoles. Rabeprazole inhibits the activity of the enzyme H + / K + ATPase ( proton pump ), thereby blocking the final stage of hydrochloric acid synthesis. This effect is dose-dependent in nature and leads to inhibition of both basal and stimulated secretion of hydrochloric acid, regardless of the stimulus.
Rabeprazole does not have anticholinergic properties.
Antisecretory activity of
After oral administration of 20 mg of rabeprazole, the antisecretory effect occurs within an hour. Inhibition of basal and stimulated secretion of hydrochloric acid 23 hours after taking the first dose of rabeprazole is 62% and 82%, accordingly, it lasts up to 48 hours. This duration of pharmacokinetic action is much longer than the predicted half-life (T1 / 2), which is about 1 hour. This effect can be explained by the binding of the drug to the H + / K + ATPase of the parietal cells of the stomach . The value of the inhibitory effect of rabeprazole on acid secretion reaches a plateau after three days of taking rabeprazole. When you stop taking secretory activity is restored within 1-2 days.
Effect on the concentration of gastrin in the blood serum
At the beginning of rabeprazole therapy, the concentration of gastrin in the blood serum increases, which is a reflection of the inhibitory effect on the secretion of hydrochloric acid. The concentration of gastrin returns to its initial level, usually within 1-2 weeks after discontinuation of treatment.
Effect on enterochromaffin-like cells
Study of biopsy specimens of the bottom and antrum of the stomach in more than 500 patients treated with rabeprazole or a comparison drug for up to 8 weeks did not reveal changes in the morphological structure of enterochromaffin-like (ECL) cells, the severity of gastritis, the frequency of atrophic gastritis metaplasia or the prevalence of Helicobacter pylori infection.
In a study of more than 400 patients receiving rabeprazole at a dose of 10 mg / day or 20 mg / day for up to 1 year, the incidence of hyperplasia was low and comparable to that for patients receiving omeprazole at a dose of 20 mg / day. Not a single case of adenomatous changes or carcinoid tumors observed
in rats was recorded.
Other effects of
There is currently no evidence that rabeprazole causes systemic effects on the central nervous system (CNS), cardiovascular, or respiratory system. When taken orally at a dose of 20 mg for 2 weeks, rabeprazole does not affect thyroid function, carbohydrate metabolism, and blood concentrations of parathyroid hormone, cortisol, estrogens, testosterone, prolactin, secretin, glucagon, follicle stimulationhormone, luteinizing hormone, renin, aldosterone and growth hormone.
Pharmacokinetics
Absorption of
Rabeprazole is rapidly absorbed from the intestine, and its maximum plasma concentration (Cmax) is reached approximately 3.5 hours after a dose of 20 mg. The change in C max and values of the area under the pharmacokinetic curve concentration-time (AUC) of rabeprazole are linear in the range of doses from 10 to 40 mg. The absolute bioavailability after oral administration of 20 mg (compared with intravenous administration) is about 52%. In addition, bioavailability does not change with multiple doses of rabeprazole. Neither the time of taking the drug during the day, nor antacids affect the absorption of rabeprazole. Reception of rabeprazole with fatty foods slows down the absorption of rabeprazole for 4 hours or more, however, neither Cmax nor the degree of absorption change.
Distribution of
In humans, the degree of binding of rabeprazole to plasma proteins is about 97%.
Metabolism
Rabeprazole is metabolized in the body in two ways. A significant part of it is metabolized systemically non-enzymatically with the formation of thioether derivatives. Rabeprazole is also metabolized in the liver via cytochrome P450 to form sulfonic and desmethyl derivatives.
In healthy volunteers, the plasma half-life is about 1 hour (varies from 0.7 to 1.5 hours), and the total clearance is 3.8 ml / min / kg.
Excretion of
After a single oral administration of 20 mg of 14C-labeled rabeprazole, about 90% of rabeprazole is excreted by the kidneys, mainly in the form of a carboxylic acid thioether, its glucuronide and in the form of derivatives of mercapturic acid. Unchanged rabeprazole in the urine is not determined. The remainder of rabeprazole taken is excreted through the intestines. The total elimination is 99.8%.
End-stage renal failure
In patients with stable end-stage renal failure who require maintenance hemodialysis (creatinine clearance <5 ml / min / 1.73 m2), rabeprazole excretion is similar to that for healthy volunteers. AUC and Cmax in these patients were approximately 35% lower than in healthy volunteers. The average T1 / 2 of rabeprazole was 0.82 hours in healthy volunteers, 0.95 hours in patients during hemodialysis, and 3.6 hours after hemodialysis. The clearance of rabeprazole in patients with kidney diseases requiring hemodialysis was approximately two times higher than 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 with healthy volunteers. Elderly patients In older patients, elimination of rabeprazole is somewhat delayed. After 7 days of taking rabeprazole in a dose of 20 mg once a day in elderly people, the AUC was approximately twice as high and Cmax increased by 60%, compared with young healthy volunteers, there were no signs of cumulation of rabeprazole. CYP2C19 polymorphism In patients with a slow metabolism through the CYP2C19 isoenzyme, after 7 days of taking rabeprazole at a dose of 20 mg per day, AUC increases 1.9 times, and the half-life is 1.6 times, compared with the same parameters for fast metabolizers “, while Cmax increases by 40%. Indications Peptic ulcer in the acute stage and ulcer anastomotic duodenal ulcer in the acute stage erosive and ulcerative gastroesophageal reflux disease or reflux esophagitis maintenance treatment of gastroesophageal reflux disease non-erosive gastroesophageal reflux disease Zollinger-Ellison syndrome and other conditions characterized by pathological hypersecretion of in combination with appropriate antibacterial therapy for the era dictations of Helicobacter pylori in patients with peptic ulcer. Contraindications Hypersensitivity to rabeprazole, substituted benzimidazoles or to the auxiliary components of the drug. Pregnancy. Breast-feeding period. Children up to 12 years. Precautions: Severe renal failure, childhood (over 12 years old). Dosage and administration Razo ® tablets are taken orally as a whole, without chewing or crushing. It was found that neither the time of day, nor food intake affect the activity of rabeprazole. In case of gastric ulcer in the acute stage and an anastomotic ulcer, it is recommended to take 20 mg orally once a day. Usually, cure occurs after 6 weeks of therapy, but in some cases, the duration of treatment may be increased. In case of peptic ulcer of the duodenum, it is recommended to take orally 20 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. In the treatment of erosive and peptic ulcer gastroesophageal reflux disease or reflux esophagitis, it is recommended to take 20 mg orally 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 maintenance therapy for gastroesophageal reflux disease, it is recommended that you take 20 mg orally once a day. The duration of treatment depends on the patient’s condition. In non-erosive gastroesophageal reflux disease, it is recommended that you take 20 mg orally once a day. If after four weeks of treatment the symptoms do not disappear, an additional examination of the patient should be carried out. After stopping the symptoms, to prevent their subsequent occurrence, the drug should be taken orally once a day upon request. 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 prescribed 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 can be up to one year. To eradicate Helicobacter pylori, it is recommended to take orally 20 mg twice a day according to a specific scheme with the appropriate combination of antibiotics. The duration of treatment is 7 days. Patients with Renal and Hepatic Insufficiency Dose adjustment in patients with renal failure is not required. In patients with mild to moderate hepatic insufficiency, the concentration of rabeprazole in the blood is usually higher than in healthy patients. Caution should be exercised when prescribing Razo ® to patients with severe liver failure. Elderly patients Dose adjustment not required. Children The safety and effectiveness of rabeprazole in children 12 years of age and older has been established for short-term (up to 8 weeks) treatment of GERD. The recommended dose for children aged 12 years and older is 20 mg 1 time per day for up to 8 weeks. The safety and effectiveness of rabeprazole in pediatric patients for other indications have not been established. Side effects Rabeprazole is usually well tolerated by patients. Side effects are generally mild or moderate and are transient. When taking rabeprazole during clinical trials, the following side effects were noted: headache, abdominal pain, diarrhea, flatulence, constipation, dry mouth, dizziness, rash, peripheral edema. The frequency 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)
is very rare (<1/10000). Immune system disorders Rarely, acute systemic allergic reactions. Disorders of the blood and lymphatic system Rarely – thrombocytopenia, neutropenia, leukopenia. Metabolic and nutritional disorders Rarely – hypomagnesemia. Disturbances from the hepatobiliary system Rarely – increased activity of “liver” enzymes, hepatitis, jaundice, hepatic encephalopathy. Disorders of the kidneys and urinary tract Very rarely – interstitial nephritis. Disorders of the skin and subcutaneous tissue Rarely – bullous rashes, urticaria very rarely – erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome. Violations of the musculoskeletal and connective tissue Rarely – myalgia, arthralgia. Reproductive system disorders Very rarely – gynecomastia. No laboratory changes were observed with rabeprazole. When taking proton pump inhibitors, you may increase the risk of bone fractures (see Special Instructions ). º °Ñ ÑÑ ² ½ ½ ¾ ² · ° ¸ ¼ ¾ ´ ¹ÑÑ ² ¸ Ñ ¸ ¾ ´ ½ ¾ ²Ñ ¼ ½ ½ ¾ ¼ ¿Ñ ¸ ¼ ½ ½ ¸ ¸ Ñ ´ ¸ ³ ¾ ºÑ ¸ ½ ¾ ¼ ² ¾ · ¼ ¾ ¶ ½ ¾ ¿ ¾ ² Ñ ½ ¸ ( ¾Ñ ½ ± ¾ »ÑÑ ¾ ¹ ´ ¾ Ñ ¼ Ñ ½ ½ ¾ ¹) º ¾ ½Ñ ½Ñ Ñ °Ñ ¸ ¸ ´ ¸ ³ ¾ ºÑ ¸ ½ ° ² ¿ » ° · ¼ ºÑ ¾ ² ¸. Ñ ¸ ¾ ´ ½ ¾ ²Ñ ¼ ½ ½ ¾ ¼ ¿Ñ ¸ ¼ ½ ½ ¸ ¸ Ñ º Ñ ¾ º ¾ ½ ° · ¾ » ¾ ¼ Ñ ¼ ½ÑÑ ° Ñ ÑÑ ³ ¾ ± ¸ ¾ ´ ¾ÑÑ Ñ ¿ ½ ¾ÑÑ Ñ. Storage Conditions At a temperature not exceeding 25 ° C. Keep out of the reach and sight of children! Expiration date 2 years (in banks), 3 years (in blisters). Do not use after the expiration date printed on the package. Pharmacy terms prescription dosage form tablets Possible Product Names Razo tablets are coated with enteric acid solution. 20 mg 30 pcs.
