active ingredient: rabeprazole;
1 capsule contains rabeprazole 10 mg or 20 mg (in the form of intestinal pellets)
auxiliary substances: neutral pellets (№16-18) coated with magnesium carbonate; gipromelloza; sodium magnesium hydroxide carbonate; talc methacrylate copolymer (type C) macrogol 6000; titanium dioxide (E 171) iron oxide red (E172) iron oxide black (E172).
Capsule is enteric coated. Basic physical and chemical properties: capsules of 10 mg: solid opaque gelatin capsules № 5 of red/white color, containing spherical or oval pellets of brown color
capsules 20 mg opaque hard gelatin capsules No. 3 of the red/brown color, containing spherical or oval pellets of brown.
Proton pump inhibitor. Code ATX a02v S04.
Mechanism of action. Rabeprazole sodium belongs to a class of antisecretory compounds, the substituted benzimidazole, has no anticholinergic properties and is an antagonist of histamine H 2 receptors, but inhibits gastric acid secretion by specific inhibition of the enzyme H +/K + ATPase at the secretory surface of parietal cells of the stomach (the acid or proton pump). The effect is dose-dependent and leads to inhibition of both basal and stimulated acid release, regardless of the irritant. Rabeprazole has slightly alkaline properties, is rapidly absorbed in all dosages and concentrated in parietal cells. Rabeprazole is converted to its active sulfenamide form by protonation and thus, reacts with available cysteine residues of the proton pump.
After receiving 20 mg of sodium rabeprazole, the antisecretory effect is observed after 1:00 and reaches a maximum in 2-4 hours. The effect of suppressing the basal function and stimulating food secretion of acid 23 hours after taking the first dose of rabeprazole was 69 and 82%, respectively, and the duration of this effect reached 48 hours. The effectiveness of rabeprazole to inhibit the secretion of acid slightly increases in the daily intake of 1 tablet, but a stable inhibition of secretion is achieved 3 days after the start of this drug. After the administration of rabeprazole secretory activity is normalized within 2-3 days.
Reducing gastric acidity regardless of any factors, including proton pump inhibitors such as rabeprazole, increases the number of bacteria in the digestive tract. Treatment with proton pump inhibitors increases the risk of gastrointestinal infections such as Salmonella, Campylobacter and Clostridium difficult .
In the course of studies, patients took 10 or 20 mg of rabeprazole once a day for 43 months. In the first 2-8 weeks of therapy, the concentration of gastrin in serum increased, which reflected inhibition of acid secretion. Gastrin concentration returned to baseline levels, usually within 1-2 weeks after cessation of treatment.
Study of biopsy samples fundus and antrum in patients treated with rabeprazole or the comparison drug for 8 weeks showed no histological changes, pronounced gastritis, increasing the frequency of atrophic gastritis, intestinal metaplasia and infection N. pylori. During the long-term treatment for 36 months, no significant changes in the results of these tests were found.
Currently, there is no data on the systemic effects of the Central nervous system, cardiovascular and respiratory system caused by the intake of rabeprazole. Oral administration of 20 mg of rabeprazole per day for 2 weeks did not affect thyroid function, carbohydrate metabolism, as well as blood concentrations of parathyroid hormone, cortisol, estrogens, testosterone, prolactin, cholecystokinin, secretin, glucagon, follicle stimulating hormone, luteinizing hormone, renin, aldosterone and somatotropic hormone.
A study involving healthy volunteers showed no clinically significant interactions between rabeprazole and amoxicillin.
Rabeprazol has no negative impact on levels in blood plasma of amoxicillin and clarithromycin together with the use of the goal of eradication of H. pylori infection in the upper part of the digestive tract.
Absorption. Barol is an intestinal capsule. Absorption of rabeprazole begins only after the capsule passes the stomach. Sodium rabeprazole is rapidly absorbed in the intestine. The maximum concentration of rabeprazole in the blood plasma is achieved 3.5 hours after taking a dose of 20 mg.the Maximum concentration in the blood plasma (with max ) and the area under the curve "concentration-time" (AUC) of rabeprazole are linear in the dose range from 10 to 40 mg. Bioavailability after oral administration of 20 mg (compared with intravenous administration) is about 52%, mainly - from the first-pass metabolism. In addition, the bioavailability does not increase with multiple doses of rabeprazole. In healthy volunteers, the plasma half-life is approximately 1:00 (0.7 to 1.5 hours) and the total clearance is estimated to be 283 ± 98 ml/min.
Distribution. In humans, the degree of binding of rabeprazole with plasma proteins is about 97%.
Metabolism, and excretion. Like other representatives of the proton pump inhibitor class, rabeprazole is metabolized by cytochrome P450 (CYP450) of the hepatic drug metabolism system. In vitro studies with human hepatic microsomes have shown that rabeprazole is metabolized by CYP450 isoenzymes (CYP2C19 and CYP3A4). At the expected level in human blood plasma, rabeprazole does not induce or suppress CYP3A4. However, studies in vitro cannot always be extrapolated regarding situations in vivo, these results show that the interaction between rabeprazole and cyclosporine is not expected. In humans, the main metabolites present in blood plasma, is thioether (M1) and carboxylic acid (M6), and secondary metabolites present in low concentrations, sulfone (M2), dimethylthiophenol (M4) and mercapturic acid conjugate (M5) . A slight antisecretory activity has only DME metabolite (MHC), but it is not present in the blood plasma.
After a single dose of 20 mg of labeled 14 with rabeprazole, unchanged rabeprazole was not shown in the urine. Approximately 90% of the specified dose aluminumalloy urine mainly as the two metabolites: mercapturic acid conjugate (M5) and carboxylic acid (M6). Part of the dose that remained was found in the feces.
Sexual characteristics. Since a single dose of 20 mg of rabeprazole is selected by body weight and human growth, sexual characteristics do not affect the pharmacokinetic parameters.
Renal failure. In patients with terminal chronic renal insufficiency, being on maintenance hemodialysis (creatinine clearance max for these patients was about 35% reduced compared with those in healthy volunteers. The average value of the half-life of 0.82 hours in healthy volunteers, 0.95 hours in patients undergoing haemodialysis and 3.6 hours in postdializnom patients. The clearance of the drug in patients with renal insufficiency, hemodialysis, was about twice as much as in healthy volunteers.
Liver failure. After a single dose of 20 mg of rabeprazole in patients with moderate chronic liver damage AUC doubled and there was a 2-3-fold increase in the half-life of rabeprazole compared to those in healthy volunteers. Thus, with daily use of the drug at a dose of 20 mg for 7 days AUC should increase at least 1.5 times, and changes in peak concentrations in blood plasma-to 1.2. The half-life of rabeprazole in patients with liver damage was 12.3 hours compared to 2.1 hours in healthy volunteers. Pharmacodynamic response (pH-metry of gastric contents) for two groups of patients was similar on therapeutic indications.
Patients of advanced age. In elderly patients, the elimination of rabeprazole is somewhat reduced. After 7 days of taking rabeprazole 20 mg a day the elderly AUC was approximately double that of C max increased by 60% and the elimination half-life increased by 30% compared to those in young healthy volunteers. However, it should be noted that there are no signs of cumulation of rabeprazole.
The CYP2C19 polymorphism. When prescribing a dose of rabeprazole 20 mg per day for 7 days in patients with delayed metabolism CYP2C19, the level of AUC and the half-life period were higher by about 1.9 and 1.6 times, respectively, compared with patients with rapid metabolism ; at the same time, C max increased by only 40%.
Active duodenal ulcer;
active benign gastric ulcer;
erosive or ulcerative gastroesophageal reflux disease (GERD)
long-term treatment of gastroesophageal reflux disease (supporting therapy for GERD)
symptomatic treatment of gastroesophageal reflux disease from moderate to very severe degree (symptomatic treatment of GERD)
in combination with appropriate antibacterial schemes for Helicobacter pylori eradication in patients with peptic ulcer of stomach and duodenum.
Hypersensitivity to rabeprazole, benzimidazole substituted or to any other component of the drug. Simultaneous use with atazanavir. Pregnancy and breast-feeding.
Interaction with other medicinal products and other forms of interaction.
the CYP450 system
The system rabeprazole metabolized in liver CYP450 enzymes, namely CYP2C19 and CYP3A4.
Studies have shown that rabeprazole has no pharmacokinetic or clinically significant interactions with warfarin, phenytoin, theophylline or diazepam, each of which is metabolized by CYP450.
Interactions caused by suppression of gastric acid secretion
Rabeprazole causes a strong and long-term decrease in hydrochloric acid production. Thus rabeprazole can interact with drugs, the absorption of which depends on the pH of the gastric contents. The simultaneous use of rabeprazole and ketoconazole or Itraconazole can lead to a decrease in the concentration of the latter in blood plasma, and the use of digoxin can lead to an increase in the concentration of the latter. Thus, some patients who use these drugs together with Barolo, should be under medical supervision to determine necessary dose adjustments.
During clinical trials, patients simultaneously with Barolo took antacids if necessary; in the course of a special study, there was no interaction of the drug with antacids, such as aluminum or magnesium hydroxide.
Concomitant use of atazanavir 300 mg/ritonavir 100 mg with omeprazole (40 mg 1 once daily) or atazanavir 400 mg with lansoprazole (60 mg 1 time per day) in healthy volunteers led to a significant reduction in the exposure of atazanavir. Absorption of atazanavir depends on pH. Although no studies have been carried out, similar results are expected for other proton pump inhibitors. Proton pump inhibitors, including rabeprazole, should not be used in combination with atazanavir.
Notification of adverse reactions the data published population pharmacokinetic studies and retrospective analyses suggest that concomitant use of methotrexate and proton pump inhibitors (predominantly at high doses) may lead to increased levels of methotrexate and/or its metabolite hydroxymethotrexate in the serum. Although no formal research was carried out.
The simultaneous use of clopidogrel and rabeprazole to healthy volunteers had no clinically important effect on the concentrations of the active metabolite of clopidogrel. Dose correction is not required.
Studies have shown that eating low-fat foods does not affect the absorption of rabeprazole. Taking rabeprazole with fatty foods may delay absorption by 4:00 or more, but the maximum concentration and level of absorption remain unchanged.
In vitro studies have found that rabeprazole inhibits cyclosporine metabolism. This level of inhibition is similar to that of drug inhibition.
Medicines are not recommended for simultaneous application with rabeprazole
Drug sidstodisable vzaimodeistviyami and risk factors
atazanavir sulfaterapevticheskoe effect atazanavir can reduce thanks to its Antisecretory action rabeprazole increases the pH of the stomach, reduces the solubility of atazanavir sulfate and thereby reduces its concentration in blood plasma
Drugs that should be administered with caution
Drug sidstodisable vzaimodeistviyami and risk factors
The concentration level of digoxin and methyldigoxin in the blood may increase thanks to its Antisecretory actions rabeprazole may increase the pH of the stomach, resulting in accelerated absorption of digoxin and methyldigoxin
gefitiniburoven concentration of Itraconazole and gefitinib in the blood can reduce thanks to its Antisecretory action rabeprazole is capable of increasing the pH of the stomach, which leads to inhibition of absorption of Itraconazole and gefitinib
Antacids containing aluminum hydroxide/magnesium hydroxyacetate of rabeprazole may be reduced by simultaneous application with antacids.
Care should be taken in appointing rabeprazole patients with known hypersensitivity to drugs. The risk of cross-hypersensitivity with other proton pump inhibitors or substituted benzimidazole is not excluded.
Use in elderly patients
Rabeprazole is metabolized exclusively in the liver. Since the physiological function of the liver may weaken with age, elderly patients may experience adverse reactions. Therefore, elderly patients should be observed and follow the recommendations on dosage and duration of treatment.
Symptomatic improvement in the treatment of rabeprazole does not exclude the presence of a malignant tumor of the stomach or esophagus, so before the appointment of rabeprazole should exclude the presence of a malignant tumor.
Patients who undergo a long course of treatment (especially those who are treated for more than 1 year) should be regularly examined.
The risk of developing cross-hypersensitivity reactions when used with other proton pump inhibitors or substituted benzimidazole is not excluded.
Patients should be warned that Barolo capsules cannot be chewed or crushed and should be swallowed whole.
Rabeprazole is not recommended for children, because there is no experience in this category of patients.
Pathological changes in blood (thrombocytopenia and neutropenia) were reported. In most cases, another etiology was not found; changes of the blood was uncomplicated and disappeared after discontinuation of rabeprazole.
The liver deviation enzymes from the norm was observed during clinical trials and during post-marketing period. In most cases, other etiologies were not found; violations were simple and disappeared after the abolition of rabeprazole.
In the course of studies in patients with mild or moderate hepatic dysfunction, there was no significant difference in the frequency of side effects when taking rabeprazole compared with that in the control group of the appropriate sex and age. The doctor should be careful when prescribing rabeprazole in the early stages of therapy for patients with severe hepatic impairment, since there are no clinical data on the use of the drug in patients of this group.
During treatment should periodically rabeprazolom hematological and biochemical testing.
Simultaneous use of atazanavir and rabeprazole is not recommended.
Treatment with proton pump inhibitors, including rabeprazole, can increase the risk of gastrointestinal infections such as Salmonella , Campylobacter and Clostridium difficult .
risk of fractures
Proton pump inhibitors, especially when applying high doses and for a long time (more than 1 year), can increase the risk of fractures to the hip, wrist and vertebrae, mainly in elderly patients or in patients with other risk factors. Observational studies suggest that proton pump inhibitors may increase the overall risk of fracture by 10-40%. Also, the risk may be increased through other factors. Patients at risk of osteoporosis should receive appropriate treatment and take vitamin d and calcium.
About cases of severe hypomagnesaemia has been reported in patients taking proton pump inhibitors for at least 3 months and, in most cases during the year. There may be serious manifestations of hypomagnesemia, such as weakness, tetany, delirium, convulsions, dizziness and ventricular arrhythmia. Most patients hypomagnesemia were resolved after discontinuation of proton pump inhibitors and hormone therapy drugs magnesium.
Patients with prolonged concomitant use of digoxin or drugs that lead to hypomagnesemia (eg, diuretics), you need to monitor the level of magnesium in the blood before and periodically during treatment.
It is recommended to monitor the function of the thyroid gland in the treatment of rabeprazole.
The features of the respiratory tests
C-urease respiratory test results may be false negative while taking proton pump inhibitors such as rabeprazole, and antibiotics such as amoxicillin, clarithromycin, and metronidazole. Therefore, to determine the presence of Helicobacter pylori respiratory tests should be carried out not earlier than 4 weeks after the end of treatment with such drugs.
Treatment perosino reflux disease is indicated for patients who have recurring reflux-symptoms, particularly heartburn and acid reflux (about 2 times a week). The use of rabeprazole can hide the symptoms of a malignant tumor (such as cancer of the stomach or intestines) and other diseases of the digestive tract. Therefore, it is necessary to exclude the presence of these diseases before the appointment of rabeprazole.
When prescribing rabeprazole to a patient with reflux disease without erosion, the doctor should confirm the effectiveness of treatment after 2 weeks of use of the drug. If the symptoms do not disappear, it is likely that reflux disease is not the cause of their occurrence. In this case, the doctor should apply another method of treatment.
If rabeprazole is prescribed for the purpose of eradication of Helicobacter pylori, it is important to pay attention to contraindications, especially the use of clinically significant adverse reactions and reservations specified in the instructions for the medical use of other drugs that are used for eradication.
Literature data suggest that the concomitant use of proton pump inhibitors and methotrexate (primarily at high doses) can increase levels of methotrexate and/or its metabolites in serum, which can lead to methotrexatesee toxicity. If it is necessary to use high doses of methotrexate should consider discontinuing treatment with proton pump inhibitors.
Use during pregnancy or breast-feeding.
There is no data on the safety of rabeprazole during pregnancy.
The use of Barolo during pregnancy is contraindicated.
It is unknown, rabeprazole penetrates into the breast milk of women. No relevant studies have been conducted.
Barol is not prescribed to women during lactation.
The ability to influence the reaction rate when driving motor transport or operating other mechanisms.
Taking into account the pharmacodynamics of rabeprazole and its characteristic profile of side effects can be considered that Barol should not adversely affect the management of vehicles or other mechanisms. However, in case of drowsiness it is recommended to avoid driving vehicles or other mechanisms.
Method of application and doses
Adults, including elderly patients.
Active duodenal ulcer and active benign gastric ulcer the recommended dose for these diseases is 20 mg 1 time per day in the morning.
In most patients with active peptic ulcer of the duodenum, the time required for healing the ulcer is up to 4 weeks. However, some patients for recovery should take the drug for an additional 4 weeks. Most patients with active benign gastric ulcer healing occurs within 6 weeks, but some patients are insensitive to the treatment for healing ulcers should take the drug further for another 6 weeks.
Erosive or ulcerative gastroesophageal reflux disease: the recommended dose for these diseases is 20 mg once a day for 4-8 weeks.
Long - term treatment of gastroesophageal reflux disease (supporting therapy GERD): for long-term treatment, you can use maintenance doses of 10 mg or 20 mg once a day (depending on the effectiveness of treatment).
Symptomatic treatment of GERD from moderate to very severe degree: patients without esophagitis drug administered at a dose of 10 mg once a day. If after 4 weeks of treatment the symptoms do not disappear, an additional examination of the patient should be carried out. As soon as the symptoms disappear, follow-up control of symptoms can be achieved using the mode "on demand": use 10 mg 1 time per day as needed.
Zollinger-Ellison syndrome: the dose is selected individually.
The recommended starting dose is 60 mg once a day. The dose can be gradually increased to 120 mg per day, if necessary. You can apply the dose to 100 mg a day. If you need to take 120 mg per day dose is divided into 2 doses of 60 mg.the Duration of treatment depends on the clinical need.
Some patients with Zollinger-Ellison syndrome received treatment with sodium rabeprazole for 1 year.
Eradication Of H. pylori: patients with H. pylori use the appropriate combination of the drug with antibiotics. Recommended the appointment within 7 days:
Barol 20 mg 2 times a day clarithromycin 500 mg 2 times daily and amoxicillin 1 g 2 times per day.
According to indications requiring admission only once a day, tablets should be taken in the morning before meals. Although there is no reception in the first half of the day, no food has demonstrated the effect on the action of rabeprazole, this mode of application is more favorable for treatment. The tablets should not be chewed or crushed they should be swallowed whole.
Impaired renal and liver function. Patients with impaired renal function or liver is not required correction doses of the drug. For information on the use of the drug for the treatment of patients with severe liver dysfunction, see "Features of application".
Barol is not prescribed to children, because there is no experience in the use of this category of patients.
The experience of intentional or accidental overdose is limited. No symptoms associated with overdose were found. The maximum dose studied did not exceed 180 mg of rabeprazole 1 time per day during treatment of the syndrome of zollingerellison.
Specific antidote for Barolo unknown. Rabeprazole well bound with blood plasma proteins and is not excreted during dialysis. In case of overdose, symptomatic and supportive therapy should be carried out.
The most common adverse reactions reported were headache, diarrhea, abdominal pain, asthenia, flatulence, rash and dry mouth. The side effects observed were mostly minor, moderate and rapid.
Infections and infestations: infection.
From the blood: anemia, eosinophilia, erythrocytopenia, lymphopenia, neutropenia, leukopenia, thrombocytopenia and leukocytosis.
The immune system: hypersensitivity (including urticaria, facial swelling, hypotension and dyspnoea erythema, acute systemic allergic reaction usually disappear after cessation of treatment).
From the metabolic: anorexia, hypomagnesemia, hyponatremia.
From the psyche: insomnia, nervousness, depression, confusion.
From the nervous system: headache, drowsiness, dizziness, weakness in the limbs, numbness of the limbs, hypesthesia, decreased hand compression force, speech disturbance, disorientation, Delery, coma.
On the part of the organ of vision: blurred vision, increased intraocular pressure.
From the side of cardiovascular system: peripheral edema, hypertension, palpitation.
From the respiratory system: cough, pharyngitis, rhinitis, bronchitis, sinusitis, glossitis.
From the digestive tract: diarrhea, nausea, vomiting, abdominal pain, constipation, flatulence, feeling of fullness and heaviness in the stomach, candidiasis, dyspepsia, dry mouth, eructation, gastritis, stomatitis, taste disorders, enteritis, esophagitis, cheilitis, heartburn , hemorrhoids.
From the digestive system: hepatitis, jaundice, hepatic encephalopathy (in rare cases, hepatic encephalopathy was observed in patients with liver cirrhosis).
The skin and subcutaneous tissue: rash, erythema (acute systemic allergic reaction usually disappear after cessation of treatment), pruritus, sweating, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, bullous reactions.
From the musculoskeletal system: non-specific pain, back pain, myalgia, leg cramps, arthralgia, fracture of the femoral neck, wrist or spine.
From the urinary system: urinary tract infections: interstitial nephritis.
From the reproductive system: gynecomastia, increased erection.
General disorders: asthenia, flu-like syndrome, malaise, chest pain, chills, fever, thirst, alopecia.
Laboratory parameters: elevated liver enzymes (Alat, aspartoacylase), lactate dehydrogenase, gamma-glutamyltransferase, alkaline phosphatase, total bilirubin, weight gain, proteinuria, increased levels of total cholesterol, triglycerides, urea nitrogen, increased levels of traxesuales globulin, CPK, uric acid, glucose urine, hyperammonemia.
Caution should be exercised when prescribing the treatment of rabeprazole patients with severe hepatic dysfunction.
Adverse reactions that have clinical significance: shock and anaphylactic reactions; pancytopenia, leukopenia, agranulocytosis, hemolytic anemia, fulminant form of hepatitis, abnormal liver function, jaundice, interstitial pneumonia, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, acute renal failure, interstitial nephritis, hyponatraemia rhabdomyolysis.
Adverse reactions that have clinical significance and typical of proton pump inhibitors: blurred vision, angioedema, bronchial spasm, mental confusion.
Store at a temperature not exceeding 25 ° C.
Keep out of reach of children.
10 capsules in a strip, 3 strips in a carton box.
For 14 capsules per strip; 1 strip in a carton box.
Category home away from home
Inventia helskea PVT Ltd, India.
Manufacturer's location and address of the place of business
F1-F1/1, Edicinal Ambernath Eat.Aw.Dee.Si. Ambernath (East) 421506, district Thane, state Maharashtra, India.
Mega Lipsiensis (Australia) PTY Ltd.
The location of the applicant
Fect.2/No. 9 Monterey Road, Dandenong, Victoria, Australia, 3175.
CAPSULES ENTERIC COATED BAROL 10
Barol-a drug that is a blocker of proton pump to reduce the production of hydrochloric acid by the stomach.
The active ingredient of the drug is rabeprazole. The absorption of the substance is carried out directly in the intestine, not in the stomach. The ingredient is bioavailable, after taking the drug is characterized by achieving a maximum level of concentration after less than 60 minutes.
Indications for appointment
Barol is used for:
The treatment of patients diagnosed with lazy stomach (activity disorder). The disease is accompanied by a functional disorder of the entire digestive system with the formation of discomfort and pain in the upper digestive tract.
In combination with antibacterial drugs in the treatment of Helicobacter pуlоri.
Treatment of mucous membranes from ulcerative lesions in the stomach or duodenum.
How to apply
The rate of the drug and the course of use are established taking into account previously used medicines, as well as on the basis of the severity of the symptoms. Standard therapy lasts no more than 6 weeks at a dosage of 10-20 mg once a day before meals.
In the absence of the desired result during the use of the drug for a duration of more than 4 weeks, it is necessary to review the feasibility of treating the patient with the use of Barol.