Rabeprazol-Mick

General characteristics. Structure:

Active ingredient: 20 mg of a rabeprazol of sodium.

Excipients: calcium a carbonate, Mannitolum, the sucrose, water purified, sugar pellets, a gidroksipropilmetiltsellyuloza 5 спз, gidroksipropilmetiltsellyuloza phthalate, cetyl alcohol, titanium dioxide, talc.

Structure of a cover of the capsule: gelatin, глицерол, sodium lauryl sulfate, the water purified dye carmoisin (E122).

Antiulcerous means.

Pharmacological properties:

Pharmacodynamics. Antiulcerous means from group of inhibitors of the protonew pump (N + / To +-ATF-azy). Is pro-medicine – in acid medium of covering cells turns into the active sulfenamidny form interacting with H+ cysteine - K+ - Atfaza (the proton pump). Inhibits (partially reversibly) H+ - K+ - to ATFAZ of obkladochny cells of a stomach and дозозависимо oppresses basal and stimulated secretion of hydrochloric acid. The anti-secretory effect is shown during 1 h after intake of a dose of 20 mg. The maximum reduction рН environments of a stomach is registered in 2-4 h after use of the first dose. In the first days reduces an average daily indicator of acidity by 61% (it makes about 88% of the decrease in secretion reached for the 8th day of treatment). Average value рН during 24 h makes 3,4; and time during which рН remains at the level of more than 3 - 55,8%. Partial dissociation of a complex with H+ - K+ - Atfaza causes smaller, than at irreversible inhibitors of the proton pump action duration. Duration of oppression of basal and stimulated secretion reaches 48 h, the stable anti-secretory effect develops in 3 days of treatment. Cancellation is not followed by a ricochet phenomenon, recovery of secretory activity happens within 2-3 days in process of synthesis of new molecules of enzyme.

Has antikhelikobakterny activity: MPK of 4-16 mkg/ml. Accelerates manifestation of antikhelikobakterny activity of a number of antibiotics. When performing triple eradikatsionny therapy (рабепразол sodium on 20 mg 2 times a day in combination with klaritromitsiny and amoxicillin) 90% of an eradikation of Helicobacter pylori are reached within 4 days. Eradikation of a helikobakter upon termination of a 7-day course of therapy is marked out respectively in 100, 95, 90 and 63% at treatment rabeprazoly sodium in combination with klaritromitsiny + metronidazole, klaritromitsiny + amoxicillin, amoxicillin + metronidazole only with klaritromitsiny. At an erosive or ulcer gastroesophageal reflux disease from the first day of treatment (10-20 mg) reduces heartburn as in day, and at night. It is effective at 8 weeks treatment of an erosive reflyuksezofagit at 84% of patients. Efficiency at morbid hyper secretory conditions is shown, including Zollinger's syndrome – Ellisona. In the first 2-8 weeks of long reception concentration of gastrin in blood serum (at a histologic research increase in number of ECL cells, frequencies of a metaplasia of intestines, colonization of H. рylori is not noted) temporarily increases.

Influence on concentration of gastrin in serum. During clinical tests patients accepted 10 mg or 20 mg of a rabeprazol of sodium of 1 times/days lasting treatment up to 43 months. In the first 2-8 weeks of therapy concentration of gastrin in serum increased that was reflection of the inhibiting effect on acid secretion. Concentration of gastrin was returned to initial level usually within 1-2 weeks after the treatment termination.

Studying of bioptat of a bottom and antral department of a stomach at more than 500 patients receiving a course of treatment rabeprazoly sodium lasting up to 8 weeks did not reveal changes of histology of enterokhromafinnopodobny cells, expressiveness of gastritis, frequency of atrophic gastritis, an intestinal metaplasia and prevalence of an infection of Helicobacter pylori. At inspection of 250 patients accepting рабепразол sodium for 36 months, significant deviations of indicators from initial level it was revealed not.

Other effects. There are no data that рабепразол sodium causes system effects from TsNS, cardiovascular and respiratory systems now. Oral administration of a rabeprazol of sodium in a dose of 20 mg/days for 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, a renin, Aldosteronum and somatotropic hormone.

Pharmacokinetics. Absorption. Rabeprazol sodium is quickly absorbed from intestines. After reception of a dose of 20 mg of Cmax of a rabeprazol in plasma it is reached approximately in 3,5 h. Changes of Cmax and AUC have linear character in the range of doses from 10 to 40 mg. Absolute bioavailability after intake of 20 mg makes about 52% in many respects because of metabolism at the first passing through a liver. Besides, bioavailability does not change at multiple dose of a rabeprazol of sodium. Meal and time of administration of drug within a day do not exert impact on absorption of a rabeprazol.

Distribution. Extent of linkng with proteins of plasma makes about 97%.

Metabolism. The main metabolites which are present at plasma are monothioester (M1) and carboxylic acid (M6), and the minor metabolites which are present at low concentration are presented by sulphone (Sq.m), dimethyl-monothioester (M4) and a conjugate of mercapturic acid (M5). Only the dimethyl metabolite (M3) has insignificant anti-secretory activity, however it is not found in plasma.

Removal. At healthy volunteers of T1/2 makes about 1 h (0,7 – 1,5 h), the total clearance makes 283+98 ml/min. After a single dose in 20 mg marked 14C rabeprazol of sodium removal of active agent in not changed look was not noted. About 90% of the specified dose are removed with urine preferential in the form of two metabolites: M5 and M6. Other part of a dose is removed with a stake.

Pharmacokinetics in special clinical cases. After a single dose of a rabeprazol of sodium in a dose of 20 mg at the similar body weight and growth no significant distinctions in pharmacokinetic parameters depending on a floor are noted.

The patients with a stable terminal renal failure needing the supporting hemodialysis (KK5 ml/min. / 1,73 sq.m) had very close distribution of a rabeprazol to that at healthy volunteers. AUC and Cmax at these patients were about 35% lower, than at healthy volunteers. T1/2 of a rabeprazol averaged 0,82 h at healthy volunteers, 0,95 h – at patients during a hemodialysis and 3,6 h – after a hemodialysis. The clearance of drug at patients with diseases of the kidneys needing a hemodialysis was approximately twice higher, than at healthy volunteers.

After a single dose of a rabeprazol of sodium in a dose of 20 mg at patients with a chronic liver failure of AUC increased twice, and T1/2 increased by 2-3 times in comparison with healthy volunteers. However after reception of a rabeprazol of sodium on 20 mg/days within 7 days of AUC Cmax – by 1,2 times increased only by 1,5 times, and. T1/2 at patients with hepatic insufficiency made 12,3 h in comparison with 2,1 h at healthy volunteers. The Pharmakodinamichesky answer (control рН in a stomach) in both groups was clinically comparable.

At patients of advanced age removal of a rabeprazol is slowed a little down. In 7 days after reception of a rabeprazol of sodium on 20 mg/days at this category of patients of AUC approximately was twice more, and Cmax – is 60% higher in comparison with young healthy volunteers. However signs of cumulation of a rabeprazol were not noted.

In case of the slowed-down metabolism of CYP2C19 after reception of a rabeprazol of sodium on 20 mg/days within 7 days of AUC T1/2 – by 1,6 times in comparison with the same parameters at "bystry" metabolizator while Cmax increases by 40% increases by 1,9 time, and.

Indications to use:

Indications to use Rabeprazola-Mick are:
- a peptic ulcer of a duodenum in an aggravation phase;
- a peptic ulcer of a stomach in an aggravation phase;
- gastroesophageal reflux disease (GERB): erosive reflux esophagitis (treatment), symptomatic treatment of GERB;
- stressful ulcers of a GIT;
- Zollingera-Ellison's syndrome or other states which are characterized by pathological hypersecretion.
Rabeprazol-Mick in a combination with antibacterial agents is used:
- for Helicobacter pylory eradikation at patients with a peptic ulcer of a stomach or chronic gastritis;
- for treatment and the prevention of a recurrence of an ulcer at patients with the peptic ulcer connected with Helicobacter pylory.

Route of administration and doses:

Inside, in the morning, to food; capsules should be swallowed entirely, without chewing.
At a peptic ulcer of a duodenum and a peptic ulcer of a stomach in a phase of an aggravation about 1 capsule (20 mg) of 1 times/days during 4-6 weeks is recommended to accept in the morning.

At most of patients healing of an ulcer happens to a peptic ulcer of a duodenum within 4 weeks. It should be noted however that some patients for healing of ulcers should accept Rabeprazol-Mick within 4 weeks.

At most of patients healing happens to a peptic ulcer of a stomach within 6 weeks, but nekotor the additional 6 weeks course of treatment Rabeprazolom-Mick can be necessary for patients for healing of ulcers.

To patients with GERB Rabeprazol-Mick on 1 capsule (20 mg) for 4-8 weeks is recommended to accept.

For the treatment of a syndrome of Zollingera-Ellison and other states which are characterized by pathological hypersecretion, the dose is selected individually. The initial dose makes 60 mg/days, then the dose is raised and appoint drug in a dose to 100 mg/days at a single dose or on 60 mg of 2 times/days. For some patients the fractional drug dosing is preferable. Treatment has to continue in process of clinical need. Some patients with Zollingera-Ellison's syndrome have treatment duration rabeprazoly made till 1 year.

For the treatment of a peptic ulcer of a duodenum or chronic gastritis connected with Helicobacter pylory infection several options of an eradikation using the corresponding combinations of antibiotics are used.

The course of treatment lasting 7 days of one of the following combinations of drugs is recommended:
- Rabeprazol-Mick on 20 mg of 2 times/days + кларитромицин on 500 mg of 2 times/days and amoxicillin on 1 g 2 times/days.
- Rabeprazol-Mick on 20 mg of 2 times/days + кларитромицин on 500 mg of 2 times/days and metronidazole on 400 mg of 2 times/days.

The best results of an eradikation exceeding 90% are observed when using a combination Rabeprazola-Mick with klaritromitsiny and amoxicillin.

Features of use:

Before therapy Rabeprazolom-Mick it is necessary to exclude existence of a malignant new growth of a stomach since administration of drug can mask symptoms and delay statement of the correct diagnosis. It is recommended to be careful at the first purpose of a rabeprazol to patients with heavy abnormal liver functions. Drug does not exert impact on function of a thyroid gland, metabolism of carbohydrates, on concentration in blood of parathyroid hormone, cortisol, estrogen, testosterone, prolactin, cholecystokinin, secretin, a glucagon, FSG, LG, renin, Aldosteronum and somatotropic hormone.

Rabeprazol-Mick is not recommended to appoint to children as now there is no experience of its use in pediatric practice.

Influence on a possibility of driving of the car, work with the equipment. Does not influence. However in case of drowsiness it is necessary to avoid these types of activity.

 

Side effects:

From bodies of a GIT: diarrhea, nausea; less often – vomiting, an abdominal pain, a meteorism, a lock; seldom – dryness in a mouth, an eructation, dyspepsia; in isolated cases – disturbance of flavoring feelings, anorexia, stomatitis, gastritis, increase in activity of transaminases.

From a nervous system and sense bodys: headache; less often – dizziness, an adynamy, sleeplessness; very seldom – nervousness, drowsiness; in some cases – a depression, vision disorders.

From a musculoskeletal system: seldom – a mialgiya; very seldom – an arthralgia, spasms of gastrocnemius muscles.

From respiratory system: seldom – an inflammation or an upper respiratory tract infection, a severe cough; very seldom – sinusitis, bronchitis.

Allergic reactions: seldom – rash, a skin itch. Other: seldom – a dorsodynia, breasts, extremities, hypostases, an infection of urinary tract, fever, a fever, a grippopodobny syndrome; in isolated cases – the increased perspiration, increase in body weight, a leukocytosis.

Interaction with other medicines:

Rabeprazol sodium is metabolized by microsomal hepatic isoenzymes of system of P450 cytochrome. Researches on healthy volunteers showed that рабепразол sodium does not enter clinically significant medicinal interaction with amoxicillin and other drugs which are metabolized by the same enzymes (warfarin, Phenytoinum, theophylline, diazepam, indirect anticoagulants).

Rabeprazol sodium causes the expressed and long decrease in production of hydrochloric acid. Therefore at simultaneous use with drugs which absorption depends from рН stomach contents, medicinal interaction was noted. Reception of a rabeprazol of sodium caused decrease in concentration of a ketokonazol in a blood plasma for 33% and increase in the minimum concentration of digoxin for 22% in healthy volunteers. Therefore at simultaneous use of a rabeprazol with ketokonazoly or digoxin it is necessary to adjust doses of the last.

Concentration of a rabeprazol and active metabolite of a klaritromitsin at simultaneous use increase by 24% and 50% respectively. It is considered as useful result of interaction at an eradikation of H. pylory.

In researches interaction of a rabeprazol with liquid antacids was not revealed. Besides, clinically significant interaction of a rabeprazol with food is not revealed.

The researches in vitro showed that рабепразол sodium is metabolized by isoenzymes of system of P450 cytochrome (CYP2C19 and CYP3A4). It is revealed that at the expected concentration in a blood plasma рабепразол sodium sodium does not render neither the stimulating, nor inhibiting influence on metabolism of CYP3A4. These researches also give the grounds to consider that рабепразол sodium does not make impact on cyclosporine metabolism.

Contraindications:

Contraindications to use are:
• pregnancy;
• lactation;
• hypersensitivity to a rabeprazol or the replaced benzimidazoles or to any ingredient of this drug.

Overdose:

Treatment: at accidental administration of drug in a high dose carry out a symptomatic and maintenance therapy. There is no specific antidote. Rabeprazol of sodium is characterized by high extent of linkng with proteins of plasma therefore badly is removed at dialysis.

Storage conditions:

Drug should be stored in the unavailable to children, protected from moisture and light place at a temperature from 15 °C to 25 °C. A period of validity - 18 months.

Issue conditions:

According to the recipe

Packaging:

On 10 capsules in yacheykrvy packagings, on 2 strip packagings in a cardboard box.