Zulbex, pills 20mg, 28pcs

Composition

1 tablet contains:

Active ingredient:  

rabeprazole sodium 20 mg;

Auxiliary substances:

mannitol (E 421);

light magnesium oxide;

hyprolose;

low-substituted hyprolose;

magnesium stearate.

Pharmacological action

of Zulbex – antiulcer.

Pharmacodynamics

Rabeprazole belongs to the class of antisecretory drugs substituted with benzimidazoles, which do not have cholinolytic or antihistamine (_H2) properties, but suppress gastric secretion by inhibiting the enzyme H+/K+-ATPase (proton pump). The effect of the drug depends on the dose and leads to suppression of basal and stimulated secretion of hydrochloric acid in the stomach, regardless of stimulating factors.

Animal studies have shown that rabeprazole quickly disappears from the plasma and gastric mucosa. Being a weak base, rabeprazole is rapidly absorbed in all dosages and accumulates in the acidic environment of the parietal cells of the stomach. Rabeprazole is converted to the sulfenamide form by protonization and then interacts with the available cysteine molecules of the proton pump.

Antisecretory action:  after oral use of 20 mg of rabeprazole, the antisecretory effect begins to develop within 1 hour, reaching a maximum in 2-4 hours. Suppression of basal and food-stimulated secretion of hydrochloric acid in the stomach 23 hours after taking the first dose of rabeprazole is 69% and 82%, respectively, and lasts up to 48 hours.

The inhibitory effect of rabeprazole on hydrochloric acid secretion slightly increases with repeated doses, reaching an equilibrium state after 3 days. After discontinuation of the drug, the secretory activity of the stomach is restored in 2-3 days.

In vitro, rabeprazole was found to have a bactericidal effect on Helicobacter pylori. H. Eradication pylori with rabeprazole and antimicrobial agents leads to a high degree of healing of mucosal lesions.

Based on the results of clinical studies, it was found that taking 20 mg of rabeprazole 2 times a day in combination with two antibiotics, for example, clarithromycin and amoxicillin, or clarithromycin and metronidazole for 1 week allows you to achieve the level of eradication of H. pylori is more than 80% in patients with gastroduodenal ulcers.

When selecting the appropriate combination for H. eradication. pylori should be guided by approved treatment standards.

In patients with persistent infection (in the presence of initially sensitive strains of microorganisms), it is necessary to take into account the possibility of developing secondary resistance to antibacterial drugs when choosing a dosage regimen.

Effect on serum gastrin:  In clinical trials, patients received rabeprazole at a dose of 10 or 20 mg once a day for up to 43 months.

The concentration of gastrin in the serum increased in the first 2-8 weeks of use, reflecting an inhibitory effect on the secretion of hydrochloric acid, and then remained stable with continued therapy. Gastrin concentrations returned to baseline values usually within 1-2 weeks after discontinuation of therapy.

Biopsy samples from the antrum and fundus of the stomach obtained from more than 500 patients treated with rabeprazole or comparative treatment for up to 8 weeks did not reveal changes in ECL-cell and histological structure, the degree of gastritis, the frequency of atrophic gastritis, intestinal metaplasia or the prevalence of H. pylori infection in more than 250 patients observed during 36 months of therapy, no significant changes in the initial conditions were detected.

Other effects:  the systemic effect of rabeprazole on the central nervous system, cardiovascular and respiratory systems has not yet been identified.

Rabeprazole administered orally at a dose of 20 mg for 2 weeks had no effect on thyroid function, carbohydrate metabolism, or circulating concentrations of parathyroid hormone, cortisol, estrogen, testosterone, prolactin, cholecystokinin, secretin, glucagon, FSH, LH, renin, aldosterone, or GH.

Clinical studies have shown that rabeprazole does not enter into a clinically significant interaction with amoxicillin, does not adversely affect the concentration of amoxicillin or clarithromycin in blood plasma when these drugs are used simultaneously for eradication H. pylori in the upper gastrointestinal tract.

Pharmacokinetics

Suction:  Zulbex® is a rabeprazole tablet coated with an enteric-soluble (stomach-stable) coating.

This form is due to the instability of rabeprazole in an acidic environment. Therefore, the absorption of rabeprazole begins only after the tablet leaves the stomach. Absorption is rapid; the_maximum plasma concentration of rabeprazole is reached approximately 3.5 hours after ingestion of a 20 mg dose. C_max and AUC are linear in the dose range from 10 mg to 40 mg.

The absolute bioavailability of an oral dose of 20 mg (compared to intravenous use) is approximately 52%, mainly due to presystemic metabolism.

With repeated use, bioavailability does not seem to increase. In healthy people, T_1/2 from blood plasma is approximately 1 h (from 0.7 to 1.5 h), and the total clearance is 283±98 ml / min. There is no clinically significant interaction associated with food intake. Neither food nor the time of taking the drug affect the absorption of rabeprazole.

Distribution:  in humans, rabeprazole is approximately 97% bound to plasma proteins.

Metabolism and elimination:  rabeprazole, like other representatives of the proton pump inhibitor class, is metabolized in the liver with the participation of cytochrome p450 (CYP450). In vitro studies with human hepatic microsomes have shown that rabeprazole is metabolized by the CYP450 isoenzymes (CYP2C19 and CYP3A4).

In these studies, rabeprazole did not inhibit or stimulate CYP3A4 at the expected human plasma concentrations. These results indicate that no interaction is expected between rabeprazole and cyclosporine.

In humans, the main metabolites detected in plasma are thioester (_M1) and carboxylic acid (_M6), while the sulfonic metabolite (_M2), desmethylthioester (_M4) and mercapturic acid conjugate (_M5) are detected in smaller amounts. Only the desmethyl metabolite (_M3) has a low antisecretory activity, but it is not detected in plasma.

After a single oral dose of 20 mg of 14C-labeled rabeprazole, unchanged rabeprazole is not excreted by the kidneys. Approximately 90% of the dose is excreted by the kidneys in the form of two metabolites: a conjugate with mercapturic acid (_M5) and carboxylic acid (_M6), as well as in the form of two unknown metabolites. The rest of the administered drug is found in the contents of the intestine.

Paul:  Adjusted for height and body weight, there were no sex differences in the pharmacokinetic parameters of rabeprazole 20 mg.

Impaired renal function:  in patients with renal insufficiency requiring hemodialysis (creatinine clearance less than 5 ml/min/1.73 m2), the distribution of rabeprazole was similar to that of healthy volunteers. AUC and_cmax in these patients were approximately 35% lower than the corresponding values in healthy volunteers.

The mean T_1/2 of rabeprazole was 0.82 hours in healthy volunteers,0.95 hours in patients on hemodialysis, and 3.6 hours after hemodialysis. The creatinine clearance of rabeprazole in patients with impaired renal function requiring maintenance hemodialysis was approximately 2 times higher than in healthy volunteers.

Impaired liver function:  after a single 20 mg dose of rabeprazole in patients with mild or moderate liver disease, the AUC increased 2-fold and the T_1/2 of rabeprazole increased 2-3-fold compared to healthy volunteers.

However, after daily oral use of a dose of 20 mg for 7 days, the AUC increased only 1.5 times, and with_max – only 1.2 times. The T_1/2 of rabeprazole in patients with impaired liver function was 12.3 hours compared to 2.1 hours in healthy volunteers. The pharmacodynamic response (control of gastric pH) in the two groups was clinically comparable.

Elderly patients:  in elderly patients, the excretion of rabeprazole is somewhat reduced. After using rabeprazole for 7 days at a daily dose of 20 mg, the AUC increased approximately 2-fold, and with_max increased by 60%, T_1/2 was increased by 30% compared to healthy young volunteers. There were no signs of rabeprazole accumulation.

The CYP2C19 polymorphism:  after oral use of rabeprazole at a dose of 20 mg in people with slow CYP2C19 metabolism, AUC and T_1/2 were approximately 1.9 and 1.6 times higher than the corresponding parameters in people with active metabolism, while C_max increased by only 40%.

Indications

• Peptic ulcer of the stomach and duodenum in the acute stage;
• Gastroesophageal reflux disease (GERD): erosive reflux esophagitis (treatment), symptomatic treatment of GERD, including long-term maintenance therapy;
• Zollinger-Ellison syndrome;
• As part of complex therapy: eradication of Helicobacter pylori in patients with peptic ulcer of the stomach and duodenum 12 or chronic gastritis;
• Treatment and prevention of recurrent peptic ulcer disease associated with Helicobacter pylori.

Use during pregnancy and lactation

Pregnancy

There are no data on the safety of using rabeprazole during pregnancy in humans. Reproductive studies in rats and rabbits showed no signs of impaired fertility or harmful effects of rabeprazole on the fetus.

The drug Zulbex is not used during pregnancy.

Lactation

It is not known whether rabeprazole is secreted in human milk, but it is secreted in rat milk. Studies in women during lactation have not been conducted.

If it is necessary to use Zulbex during lactation, breast-feeding should be discontinued.

Contraindications

Hypersensitivity to the Active ingredient or auxiliary components of the drug, pregnancy, breast-feeding, childhood (no experience of use).

With caution

Severe renal failure.

Side effects

From the hematopoietic system: rarely-neutropenia, leukopenia, thrombocytopenia, leukocytosis.

From the immune system: rarely-hypersensitivity reactions.

Metabolic and nutritional disorders: rarely — anorexia, weight gain; very rarely-hyponatremia.

Nervous system disorders: often — headache, dizziness, insomnia; infrequently-drowsiness, nervousness; rarely-depression; very rarely-confusion.

From the side of the senses: rarely-visual impairment.

From the CCC side: very rarely — peripheral edema.

Respiratory system disorders: often — cough, pharyngitis, rhinitis; infrequently-bronchitis, sinusitis.

From the digestive system: often — diarrhea, vomiting, nausea, abdominal pain, constipation, flatulence; infrequently-dyspepsia, dry oral mucosa, belching; rarely-gastritis, stomatitis, taste changes, hepatitis, jaundice, hepatic encephalopathy.

From the side of the skin: infrequently-rash, erythema; rarely-pruritus, sweating, bullous rash; very rarely-erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome.

From the musculoskeletal system: often-non-specific pain, back pain; infrequently-myalgia, calf muscle cramps, arthralgia.

From the urinary system: infrequently-urinary tract infections; rarely-interstitial nephritis.

From the side of the reproductive system: very rarely — gynecomastia.

Laboratory parameters: infrequently-increased activity of liver enzymes.

Other services: often-asthenia, a flu-like disease.

Interaction

Rabeprazole causes persistent and prolonged suppression of hydrochloric acid secretion in the stomach. Interactions with drugs whose absorption depends on pH values may occur. Concomitant use of rabeprazole with ketoconazole or itraconazole may lead to a significant decrease in their concentration in blood plasma, and therefore it may be necessary to adjust the dose of these drugs.

Proton pump inhibitors, including rabeprazole, should not be used concomitantly with atazanavir.

Rabeprazole does not have a clinically significant interaction with amoxicillin and with other drugs metabolized by cytochrome CYP450 enzymes, such as warfarin, phenytoin, theophylline and diazepam.

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

Concentrations of rabeprazole and the active metabolite clarithromycin in plasma with simultaneous use increased by 24% and 50%, respectively. Reduces the concentration of ketoconazole by 33%, digoxin by 22%.

How to take, course of use and dosage

Inside, whole, without chewing or breaking.

Peptic ulcer of the stomach and duodenum 12 in the stage of exacerbationabout 20 mg 1 time a day, in the morning.

In most patients, an active duodenal ulcer heals within four weeks. However, some patients may need another 4 weeks for the ulcer to fully heal. Active benign gastric ulcer in most patients heals within six weeks.

However, in a small number of patients, it may take another six weeks for complete healing.

Gastroesophageal reflux disease (GERD): erosive reflux esophagitis (treatment), symptomatic treatment of GERD:

Take 20 mg once a day for four to eight weeks. With long-term therapy, a maintenance dose of Zulbex can be used-10-20 mg once a day, depending on the patient’s response to treatment.

Symptomatic treatment of GERD:

10 mg once a day in patients without esophagitis. If symptoms cannot be controlled within 4 weeks, an additional examination of the patient should be performed. After the patient’s condition improves, further control of symptoms can be carried out by taking 10 mg 1 time a day, on request.

Zollinger-Ellison syndrome:

The recommended starting dose for adults is 60 mg once a day. The dose can be increased to 120 mg per day, depending on the individual needs of the patient. You can prescribe a daily dose of up to 100 mg 1 time a day. A dose of 120 mg may require 6 multiple doses,60 mg 2 times a day. Therapy is carried out as long as there are appropriate clinical indications.

H. pylori eradication in patients with gastric and duodenal ulcer or chronic gastritis:patients with H. pylor should undergo eradication therapy. The following combinations of drugs with a course of 7 days are recommended: ® The drug Zulbex 20 mg 2 times a day + clarithromycin 500 mg 2 times a day and amoxicillin 1 g 2 times a day.

If the eradication regimens require the use of drugs once a day, the drug Zulbex should be taken in the morning, before breakfast; the time of day and food intake do not affect the activity of rabeprazole.

Impaired renal and/or hepatic function:No dose adjustment of Zulbex is required.

Children’s age: Due to insufficient data on the efficacy and safety of rabeprazole, Zulbex is not used in children.

Overdose

The existing experience of deliberate or accidental overdose with rabeprazole is limited. The maximum prescribed amount of the drug taken did not exceed 60 mg twice a day or 160 mg once a day.

The effects were insignificant and corresponded to the known spectrum of adverse reactions, which passed independently without any additional medical intervention. The specific antidote is unknown. Dialysis is ineffective.

Treatment: symptomatic.

Special instructions

Reduction of the severity of symptoms during therapy with Zulbex® It does not exclude the presence of malignant neoplasms in the stomach or esophagus, so before starting therapy, it is necessary to conduct an examination in order to exclude gastrointestinal neoplasms.

Patients receiving long-term therapy with Zulbex® (especially for more than one year) should be regularly evaluated.

The risk of cross-reactions with other proton pump inhibitors or with substituted benzimidazoles cannot be excluded.

The patient should be warned that the tablets should be swallowed whole, without chewing or breaking.

The drug Zulbeks® it is not recommended to prescribe to children, because there is no experience of using the drug in this group of patients.

There are reports from a post-marketing study of the development of blood dyscrasias (cases of thrombocytopenia and neutropenia) against the background of rabeprazole use. In most cases, when it was not possible to find out alternative causes of these conditions, they did not cause complications and passed after the withdrawal of rabeprazole.

Against the background of the use of Zulbex®, a change in the activity of liver enzymes may occur after discontinuation of the drug.

In the study, patients with mild or moderate hepatic impairment did not have significant problems related to the safety of rabeprazole use, compared with a control group of healthy patients, corresponding by gender and age. Due to the lack of clinical data on the use of rabeprazole in patients with severe hepatic impairment, caution is recommended when using Zulbex® in this group of patients.

Influence on the ability to drive vehicles and other complex mechanisms: 

based on the properties of rabeprazole, it is unlikely that the drug Zulbex® can interfere with the ability to drive vehicles or affect the operation of technical devices.

In case of side effects (drowsiness, dizziness, confusion), you should stop driving a vehicle and work that requires increased concentration of attention and speed of psychomotor reactions.

Form of production

Enteric coated tablets

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

2 years

Active ingredient

Rabeprazole

Conditions of release from pharmacies

By prescription

Dosage form

Tablets