Geerdin

General characteristics. Structure:

Active ingredient: 20 mg of a rabeprazol of sodium in 1 bottle.

Excipients: mannitol (E421), sodium carbonate.

The most bystry, strong and quality safe IPP which is quickly reducing acidity after the first use.

Pharmacological properties:

Pharmacodynamics. Action mechanism. Sodium рабепразол belongs to a class of anti-secretory connections, the replaced benzimidazoles, has no anticholinergic properties and H2 receptors are not an antagonist histamine, but suppress secretion of gastric acid by specific oppression of H+/K enzyme +-ATF-azy on the secretory surface of covering cells of a stomach (the acid or proton pump). The effect is dozozavisimy and leads to suppression of both basal, and stimulated release of acid irrespective of an irritant.

Sodium рабепразол has alkalescent properties, in all doses quickly is absorbed and concentrates in covering cells. Sodium рабепразол turns into an active sulfenamidny form by protonation and, thus, reacts with the available remains of cysteine of the proton pump.

Anti-secretory activity. After oral administration of 20 mg of sodium of a rabeprazol the anti-secretory effect is observed in 1 hour and reaches a maximum in 2-4 hours. The effect of suppression of basal function and stimulation by food of secretion of acid in 23 h after reception of the first dose of a rabeprazol of sodium made 69 and 82% respectively, and duration of this effect reached 48 hours. Efficiency of a rabeprazol of sodium on acid secretion oppression amplifies a little in the course of daily reception of one tablet, but stable oppression of secretion is reached in 3 days after the beginning of reception of this drug. After completion of reception of a rabeprazol of sodium secretory activity is normalized within 2-3 days.

Decrease in acidity of a stomach irrespective of any factors, including inhibitors of a proton pomp, such as рабепразол, increases quantity of bacteria in digestive tract. Treatment by inhibitors of a proton pomp can increase risk of gastrointestinal infections, such as Salmonella, Campylobacter and Clostridium difficile.

Influence on concentration of gastrin in serum. Concentration of gastrin in serum within the first weeks of therapy can increase, but it is returned to initial levels, as a rule, within 1-2 weeks after the treatment termination.

Other effects. There are no data on system effects from TsNS, the cardiovascular and respiratory system caused by reception of a rabeprazol of sodium for today. Oral administration of 20 mg of a rabeprazol of sodium in days within 2 weeks did not exert impact on function of a thyroid gland, metabolism of carbohydrates, and also on concentration in blood of parathyroid hormone, cortisol, estrogen, testosterone, prolactin, cholecystokinin, secretin, a glucagon, follicle-stimulating hormone (FSH), the luteinizing hormone (LH), a renin, Aldosteronum and somatotropic hormone.

Rabeprazol does not exert a negative impact on levels in a blood plasma of amoxicillin and a klaritromitsin at simultaneous use for the purpose of an eradikation of an infection of H. pylori in an upper part of digestive tract.

Pharmacokinetics. Absorption. Absorption of sodium of a rabeprazol begins only after the tablet passes a stomach. Sodium рабепразол it is quickly absorbed from intestines. Peak concentration of a rabeprazol in plasma are reached approximately in 3,5 h after reception of a dose of 20 mg. Peak concentration in plasma (Cmax) and AUC of a rabeprazol have linear character in the range of doses from 10 to 40 mg. Absolute bioavailability after oral administration of 20 mg (in comparison with intravenous administration) makes about 52%, generally for metabolism of the first passing. Besides, bioavailability does not increase at multiple dose of a rabeprazol of sodium.

Distribution. At the person extent of linkng of a rabeprazol of sodium with proteins of plasma makes about 97%.

Metabolism and excretion. As well as other representatives of a class of inhibitors of a proton pomp, рабепразол it is metabolized by P450 (CYP450) cytochrome of hepatic system of metabolism of drugs.

At the person the main metabolites which are present at plasma is monothioester (M1) and carboxylic acid (M6), and the minor metabolites which are present at low concentration are presented by sulphone (Sq.m), dimethylmonothioester (M4) and a conjugant of mercapturic acid (M5). Only the dimethyl metabolite (MZ) has insignificant anti-secretory activity, however it is not present at plasma.

After a single dose of 20 mg of a marked 14C-rabeprazol of sodium of not changed rabeprazol in urine did not find. About 90% of the specified dose eliminirutsya with urine preferential in the form of two metabolites: conjugant меркаптурово ї acid (M5) and carboxylic acid (M6).

Renal failure. The patients with a terminal chronic renal failure who are on the supporting hemodialysis (clearance of creatinine less than 5 ml/min. / 1,73 sq.m), distribution of a rabeprazol of sodium had very similar to it at healthy volunteers. AUC of a rabeprazol of sodium and Cmax for such patients almost for 35% are raised in comparison with those at healthy volunteers. Average value of an elimination half-life makes 0,82 hours at healthy volunteers, 0,95 hours at the patients who are on a hemodialysis and 3,6 hours in post-dialysis patients. The patients with a renal failure who are on a hemodialysis had a clearance of medicine approximately twice more, than at healthy volunteers.

Liver failure. After a single dose of 20 mg of a rabeprazol of sodium at patients with moderate chronic damage of a liver of AUC it is doubled and 2-3 discontinuous increase of an elimination half-life of a rabeprazol in comparison with those at healthy volunteers were observed. Thus, at daily administration of drug in a dose of 20 mg within 7 days of AUC change of peak concentration in Cmax plasma – to 1,2 has to increase not less than by 1,5 times, and. The elimination half-life of sodium of a rabeprazol at patients with damage of a liver made 12,3 hours in comparison with 2,1 hours at healthy volunteers. Pharmakodinamicheskoye the answer (a rn-metriya of gastric contents) for two groups of patients was similar on therapeutic indicators.

Patients of advanced age. At patients of advanced age elimination of a rabeprazol of sodium is a little reduced. After 7 days of reception of a rabeprazol of sodium on 20 mg a day at elderly people of AUC was approximately twice bigger, Cmax increased by 60%, and T1/2 increased by 30% in comparison with those at young healthy volunteers. However it should be noted lack of signs of cumulation of a rabeprazol of sodium.

Polymorphism of CYP2C19. At appointment within 7 days of a dose of 20 mg of a rabeprazol of sodium a day at patients who have the slowed-down metabolism CYP2C19 the AUC levels (the areas under a curve) and T1/2 (semi-removal time) were higher approximately in 1,9 and 1,6 times respectively in comparison with those at patients with bystry metabolism, at the same time Cmax increased only by 40%.

Indications to use:

Rabeprazol in the form of the lyophilized powder for preparation of solution for injections appoint in cases when use of a peroral form is impossible, namely:

• an aggravation of a peptic ulcer of a stomach or duodenum with bleeding and heavy erosion;

• short-term treatment of a gastroesophageal reflux disease with erosion and ulcers;

• aspiration prevention to acid contents of a stomach;

• Zollingera-Ellison's syndrome.

Route of administration and doses:

Intravenous administration is only recommended to a rabeprozol when oral administration is impossible. As soon as there is possible a purpose of a peroral form to a rabeprozol, intravenous administration should be cancelled.

The recommended dose - 20 mg to a rabeprozol of 1 times a day.

The prepared solution should be entered only intravenously.

For introduction in the form of an injection contents of a bottle to dissolve in 5 ml of solvent (water for injections, 0,9% chloride sodium solution) and to enter into a vein slowly - within 5-15 min.

For introduction in the form of infusion at first to dissolve bottle contents in 5 ml of water of injections, the received solution transfer to a bottle 0,9% of solution of sodium of chloride of 100 ml or to 5% solution of glucose of 100 ml. Before introduction it is necessary to estimate visually completeness of dissolution and to exclude discolorations, existence of a deposit and change of transparency of solution. To enter solution of 100 ml within 15-30 min. and to use within 4 hours. Unused solution is not recommended to be stored

Features of use:

Researches of safety of use of a rabeprazol to pregnant women were not conducted therefore use of a rabeprazol is contraindicated during pregnancy. It is unknown whether gets sodium рабепразол into breast milk. The corresponding researches were not conducted therefore women should not appoint during feeding a breast.

There is no sufficient experience of use of drug Geerdin to children therefore do not apply at patients of this age group.

It is necessary to be careful at purpose of a rabeprazol to patients with the known hypersensitivity to drugs. Risk of cross hypersensitivity with other inhibitors of a proton pomp (IPP) or are replaced benzimidazole it is not excluded.

At use of drug for patients of advanced age it is necessary to remember what рабепразол is metabolized only in a liver. As with age physiological function of a liver can be weakened, patients of advanced age can have side reactions. Therefore patients of advanced age it is necessary to observe and follow recommendations about a dosage and duration of treatment.

Before an initiation of treatment Geerdin it is necessary to exclude malignant new growths of a stomach and gullet as administration of drug can mask symptoms and delay detection of a tumor.

Patients with a long course of treatment rabeprazoly should be inspected regularly.

The risk of cross hypersensitivity with other inhibitors of a proton pomp or replaced benzimidazole is not excluded.

It was reported about pathological changes of blood (thrombocytopenia and a neutropenia) at use of a rabeprazol. In most cases other etiology was not found; cases were uncomplicated and disappeared after cancellation of a rabeprazol.

During treatment rabeprazoly it is recommended to hold hematologic and biochemical testings periodically.

At use of inhibitors of a proton pomp within three months and more patients can have a hypomagnesiemia (symptomatic and symptomless), and also such symptoms as arrhythmia, spasms, a tetany are shown. Treatment of a hypomagnesiemia demanded the termination of administration of drugs of inhibitors of a proton pomp and purpose of the replacement adjusting therapy from most of patients magnesium drugs. To patients, possibly will it is long to take medicine (for example digoxin), or drugs which can lead to a hypomagnesiemia (for example diuretics) it is necessary to monitor magnesium level in blood prior to the beginning of and during treatment.

Cases of an aberration of liver enzymes were observed. In most cases other etiology was not found; cases were uncomplicated and disappeared after cancellation of a rabeprazol.

At patients with easy or moderate abnormal liver functions considerable cancellation of frequency of side effects at reception of a rabeprazol in comparison with control group of the corresponding gender and age was not observed. The research on patients with a heavy liver failure was not conducted therefore it is necessary to apply with care рабепразол patients with a heavy liver failure. The dose at a liver failure needs to be lowered.

Owing to the insufficient number of clinical data on intravenous use of a rabeprazol for patients with essential disturbances of functions of a liver рабепразол such patient it is appointed in urgent cases in a half dose (10 mg) under observation of the doctor.

There are no clinical data on use of a rabeprazol to patients with heavy renal failures therefore Geerdin to patients with a heavy renal failure is not recommended to appoint.

Function of a thyroid gland. It is recommended to control function of a thyroid gland at treatment rabeprazoly.

Features of carrying out respiratory tests.  Results S-ureaznikh of respiratory tests can be false-negative during reception of inhibitors of a proton pomp, such as рабепразол, and antibiotics, such as amoxicillin, кларитромицин and metronidazole. Therefore for Helicobacter pylori existence definition it is necessary to carry out respiratory tests not earlier than in 4 weeks upon termination of treatment by such drugs.

At use of drug there is a risk of changes. Some observatsiyn a research assume that inhibitors of a proton pomp can increase risk osteoporosis-zavisimymykh of fractures of hip, to a wrist and vertebrae. The risk of changes grew at patients who lasted (more than 1 year) received high doses of IPP.  

Carefully patients should use drug with respiratory insufficiency.

Simultaneous use is contraindicated to an atazanavir and a rabeprazol (see the section "Interaction with Medicines and Other Types of Interactions"). 

Treatment by inhibitors of a proton pomp, including рабепразол, increases risk of developing of the gastrointestinal infections caused by such activators as Salmonella, Campylobacter and Clostridium difficille.

Ability to influence speed of response at control of motor transport or work with other mechanisms. In case of developing of dizziness, drowsiness, it is recommended to avoid driving or work with other mechanisms.

Side effects:

Side effects of a rabeprazol the main insignificant, moderate and quickly pass.

Infections and invasions: infections, intersticial pneumonia.

Blood and lymphatic system: anemia, erythrocytopenia, pancytopenia, leukopenia, agranulocytosis, eosinophilia, lymphopenia, neutropenia, leukopenia, thrombocytopenia, leukocytosis and hemolitic anemia.

From immune system: rash and dryness in a mouth, hypersensitivity reactions, including shock, anaphylactoid reactions, urticaria, a face edema, arterial hypotension and an asthma; acute system allergic reactions, usually disappear after the treatment termination.

From metabolism: anorexia, hypomagnesiemia, hyponatremia.

Mental disorders: sleeplessness, drowsiness, excitement, nervousness, depression, confusion of consciousness, delirium, coma.

From a nervous system: a headache, dizziness, weakness in extremities, numbness of extremities, a hypesthesia, an adynamy, decrease in force of compression, disturbance of the speech, a disorientation.

From organs of sight: vision disorder, increase in intraocular pressure.

Vascular frustration: peripheral hypostases, hypertensia, palpitation.

From respiratory system: cough, pharyngitis, rhinitis, bronchitis, sinusitis, glossitis, Quincke's disease, bronchial spasm.

From a digestive tract: diarrhea, nausea, vomiting, an abdominal pain, a lock, a meteorism, dyspepsia, rash and dryness in a mouth, an eructation, gastritis, stomatitis, disturbances of taste, overflow and weight in a stomach, candidiasis, enteritis, an esophagitis, a cheilitis, heartburn, a meteorism, hemorrhoids.

Disorders of a liver and biliary tract: hepatitis, a fulminantny form of hepatitis, an abnormal liver function, jaundice, hepatic encephalopathy (in rare instances hepatic encephalopathy was observed at patients with cirrhosis).

From skin and hypodermic fabrics: rash, multiformny erythema, erythema, violent reactions and acute system allergic reactions, itch, perspiration, toxic epidermal necrosis (TEN), Stephens-Johnson's syndrome.

From a musculoskeletal system: nonspecific pain / dorsodynia, mialgiya, spasms of legs, arthralgia, рабдомиолиз.

From kidneys and urinary system: acute renal failure, infections of urinary tract, intersticial nephrite.

From reproductive system: gynecomastia, strengthening of an erection.

General disturbances and local reactions: adynamy / weakness, a grippopodobny syndrome, an indisposition, a stethalgia, to back, fever, a fever, heat, thirst, an allopecia, the increased perspiration, changes in an injection site.

Results of researches: increase in level of liver enzymes (ALT, nuclear heating plant), LDG, gamma глутамилтрансферазы, alkaline phosphatase, general bilirubin, increase in body weight, proteinuria, increase in level of the general cholesterol, triglycerides, urea nitrogen, increase in the TSG, KFK level, uric acid, increase in glucose of urine, giperammoniyemiya.

Side reactions which have clinical value:

1) Shock and anaphylactic reactions.

2) Pancytopenia, leukopenia, agranulocytosis and hemolitic anemia.

3) Fulminantny form of hepatitis, abnormal liver function, jaundice.

4) Intersticial pneumonia.

5) Toxic epidermal necrolysis, Stephens-Johnson's syndrome, multiformny erythema.

6) Acute renal failure, intersticial nephrite.

7) Hyponatremia.

8) Rabdomioliz.

Side reactions which have clinical value and are inherent to inhibitors of a proton pomp:

1) Vision disorder.

2) Quincke's disease, bronchial spasm.

3) Confusion of consciousness.

Interaction with other medicines:

CYP-450 system. Rabeprazol of sodium is metabolized by system of CYP-450 liver enzymes, namely CYP2C19 and CYP3A4.

Researches showed what рабепразол sodium has no pharmacokinetic or clinically significant interactions with warfarin, Phenytoinum, theophylline or diazepam, each of which is metabolized by CYP-450.

The interactions caused by oppression of secretion of gastric acid. Sodium рабепразол causes strong and long decrease in production of gastric acid. Thus, рабепразол in principle can interact with drugs which absorption depends on an indicator рН gastric contents. Simultaneous use of a rabeprazol of sodium and a ketokonazol or itrakonazol can lead to decrease in concentration of the last in plasma, and use with digoxin can cause increase in concentration of the last. Thus, certain patients who use the specified drugs together with Geerdin should be under observation of the doctor for definition of need of dose adjustment.

Antacids. At clinical tests patients along with Geerdin accepted if necessary antacids, during the special research Geerdin's interaction with antacids, such as aluminum or magnesium hydroxide was not observed.

Atazanavir. Simultaneous use of an atazanavir of 300 mg / ритонавира 100 mg with omeprazoly () or an atazanavira of 400 mg with lanzoprazoly (60 mg of 1 times a day) at healthy volunteers led 40 mg of 1 times a day to considerable decrease in exposure of an atazanavir. Absorption of an atazanavir depends from рН. Though researches were not conducted, expected similar results of use of other inhibitors of a proton pomp. Inhibitors of a proton pomp, including рабепразол, should not be applied in a combination with atazanaviry (see the section "Features of Use").

Food. Researches showed that the use of food with the low content of fats does not influence absorption of a rabeprazol of sodium. Reception of a rabeprazol of sodium with greasy food can detain absorption for 4 hours and more, however the maximum concentration and level of absorption remain not changed.

Cyclosporine. The researches in vitro showed what рабепразол sodium inhibits cyclosporine metabolism. This level of inhibition similar to inhibition level omeprazoly.

Atazanavira sulfate. Therapeutic action of an atazanavir can decrease. Thanks to anti-secretory action Geerdin raises рН a stomach, reduces solubility of sulfate of an atazanavir and by that reduces its concentration in a blood plasma.

Digoxin, methyldigoxin. Level of concentration of digoxin and methyldigoxin in blood can increase. Thanks to the to anti-secretory action Geerdin can increase рН a stomach that leads to the accelerated absorption of digoxin and methyldigoxin.

Itrakonazol, гефитиниб. Level of concentration of an itrakonazol and gefitinib in blood can decrease. Thanks to the anti-secretory action Geerdin is capable to increase рН a stomach that leads to inhibition of absorption of an itrakonazol and gefitinib.

The antacids containing aluminum hydroxide, magnesium hydroxide. Concentration of a rabeprazol can decrease at simultaneous use with antacids.

Contraindications:

Hypersensitivity to a rabeprazol, replaced with benzimidazole or to any other ingredient of drug.

Not to apply together with atazanaviry.

Overdose:

There are no data on overdose by drug. Most established influence did not exceed 180 mg of a rabeprazol during treatment of a syndrome Zollingera-Ellinson once a day. Strengthening of symptoms of side effect is possible.

Treatment: at accidental administration of drug in high doses it is necessary to carry out the supporting and symptomatic therapy. There is no specific antidote. Rabeprazol well contacts proteins of a blood plasma therefore it is badly removed at dialysis.

Storage conditions:

To store at a temperature not over 25 ºС in original packaging in the place, unavailable to children. Period of validity 2 years.

Issue conditions:

According to the recipe

Packaging:

On 20 mg of a rabeprazol of sodium in bottles on 10 ml. On 1 bottle in a cardboard pack.