Pariet: instructions for using the medicine, structure, Contraindications

Active material: Rabeprazole
When ATH: A02BC04
CCF: Inhibitor N⁺-K⁺-ATPase. Anti-ulcer drug
ICD-10 codes (testimony): E16.8, K21, K21.0, K25, K26, K27
When CSF: 11.01.03
Manufacturer: JOHNSON & JOHNSON LTD (Russia)

Pariet: dosage form, composition and packaging

Pills, enteric coated Pink colour, round shape, lenticular, on one side of the marking ink “∈241”.

Excipients: mannyt (mannitol), magnesium oxide, giproloza low substituted (low substituted hydroxypropyl cellulose), giproloza (hydroksypropyltsellyuloza), magnesium stearate, ethyl cellulose, gipromellozы phthalate, diacetylated monoglyceride, talc, Titanium dioxide, iron oxide red, Anhydrous ethanol (evaporates during manufacture), Purified water (evaporates during manufacture), carnauba wax, edible ink gray F6, Butanol (evaporates during manufacture).

7 PC. – blisters (1) – packs cardboard.
7 PC. – blisters (2) – packs cardboard.
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.

Pills, enteric coated light yellow, round shape, lenticular, on one side of the marking ink “∈243”.

Excipients: mannyt (mannitol), magnesium oxide, giproloza low substituted (low substituted hydroxypropyl cellulose), giproloza (hydroksypropyltsellyuloza), magnesium stearate, ethyl cellulose, gipromellozы phthalate, diacetylated monoglyceride, talc, Titanium oxide, iron oxide yellow, Anhydrous ethanol (evaporates during manufacture), Purified water (evaporates during manufacture), carnauba wax, edible red ink A1, Butanol (evaporates during manufacture).

7 PC. – blisters (1) – packs cardboard.
7 PC. – blisters (2) – packs cardboard.
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.

Pariet: pharmachologic effect

Anti-ulcer drug. Inhibitor N⁺-K⁺-ATPase (proton pump).

Mechanism of action. Rabeprazole sodium belongs to a class of antisecretory compounds, which chemically are substituted benzimidazoles. The drug inhibits the activity of the enzyme N⁺-K⁺-ATPase, thereby blocking the final step of the synthesis of hydrochloric acid. This effect is dose-dependent and leads to inhibition of both basal, and stimulated acid secretion irrespective of stimulus. As a weak base in any dose rabeprazole is rapidly absorbed and concentrated in the acidic environment of the parietal cells.

Antisecretory Activity. After oral administration at a dose of rabeprazole 20 mg antisecretory effect occurs for 1 hours and reaches a maximum after 2-4 no. Inhibition of basal and stimulated acid secretion through food 23 hours after the first dose of rabeprazole sodium was 62 and 82% respectively, and the duration of action is achieved 48 no. The inhibitory effect on the secretion of rabeprazole sodium acid slightly increased during daily administration of 1 tab., stable inhibition of secretion is achieved through 3 day after the beginning of drug administration. After receiving rabeprazole secretory activity recovered through 2-3 day.

It notes the role of Helicobacter pylori in the development of peptic ulcer disease, including gastric ulcer and duodenal ulcer. Helicobacter pylori is a major factor in the development of gastritis and ulcers in these patients. Recent studies suggest a causal relationship between Helicobacter pylori and gastric carcinoma.

In vitro it was found, that rabeprazole has a bactericidal effect on Helicobacter pylori. Helicobacter pylori eradication with Pariet^® and antimicrobials leads to a high degree of healing of mucosal lesions. According to the results of controlled randomized clinical trials found, that taking rabeprazole 20 mg 2 times / day in combination with two antibiotics, eg, klaritromiцinom amoksiцillinom or klaritromiцinom metronidazolom tecenie 1 a week can achieve the level of Helicobacter pylori eradication more 80% in patients with gastro-duodenalʹnymi âzvami. As expected, tendency to low eradication was observed in patients with a baseline resistance to metronidazole. When selecting a suitable combination for Helicobacter pylori eradication should be guided by the approved standards of treatment. In patients with persistent infection (if there is originally sensitive strains of microorganisms) must take into account the possibility of the development of secondary resistance to antibiotics when selecting treatment.

Influence on concentrations of serum gastrin. During clinical trials, patients were 10 mg or 20 mg rabeprazole 1 time / day when the duration of treatment up 43 Months. First 2-8 weeks of treatment serum gastrin concentration increased, a reflection-inhibiting effect on acid secretion. The concentration of gastrin returned to baseline generally within 1-2 weeks after cessation of treatment.

The study of biopsies bottom and antrum more than 500 patients, receiving treatment for up to rabeprazole 8 weeks, Histology revealed no changes in cell enterohromafinnopodobnyh, severity of gastritis, frequency of atrophic gastritis, intestinal metaplasia and the prevalence of Helicobacter pylori infection. The examination 250 patients, taking rabeprazole for 36 Months, significant deviations from the baseline indicators were found.

Other effects. Currently, there is no evidence, rabeprazole that causes systemic effects of CNS, cardiovascular and respiratory systems. Rabeprazole when administered in a dose 20 mg / day for 2 weeks had no effect on thyroid function, glycometabolism, and also on the blood concentration of the parathyroid hormone, Cortisol, Estrogen, Testosterone, prolactin, cholecystokinin, secretin, glucagon, FSH, LG, Renin, Aldosterone and MES.

Pariet: pharmacokinetics

Absorption

Rabeprazole is rapidly absorbed from the intestine. Upon receiving a dose 20 mg C_max rabeprazole in plasma is reached after about 3.5 no. C Changes_max and AUC are linear over a dose range from 10 to 40 mg. The absolute bioavailability after oral administration 20 mg (compared to / in the introduction) is about 52% largely due to metabolism in “first pass” through the liver. Besides, bioavailability does not change during multiple dose rabeprazole. Ingestion time and dosing during a day have no effect on the absorption of rabeprazole.

Distribution

The man rabeprazole binding to plasma proteins is approximately 97%.

Metabolism

The main metabolites, present in human plasma, They are thioester (M1) and carboxylic acid (M6), and secondary metabolites, present in low concentrations, presented sulfone (M2), demetiltioefirom (M4) and the conjugate acid mercapturic (M5). Minor antisecretory activity has only dimethyl metabolite (M3), however it is not detected in the plasma.

Deduction

In healthy volunteers T_1/2 is about 1 no (0.7-1.5 no), total clearance is 283 ± 98 mL / min.

About 90% excreted in the urine primarily as metabolites two: M5 and M6. About 10% excreted in the feces.

Pharmacokinetics in special clinical situations

After receiving a single dose of rabeprazole 20 mg with similar weight and height are no significant differences in pharmacokinetic parameters based on gender is not marked.

In patients with stable renal disease, requiring maintenance hemodialysis (KK≤5 ml / min / 1.73 m²) distribution of rabeprazole was very close to that in healthy volunteers. AUC and C_max these patients were approximately 35% below, than in healthy volunteers. The average T_1/2 rabeprazole was 0.82 hours in healthy volunteers, 0.95 no – patients during hemodialysis and 3.6 no – after hemodialysis. The clearance of the drug in patients with kidney disease, requiring hemodialysis, It was approximately 2 times higher, than in healthy volunteers.

After receiving a single dose of rabeprazole 20 mg in patients with chronic liver disease in increased AUC 2 times, and T_1/2 increased in 2-3 fold compared with healthy volunteers. However, after taking a dose of rabeprazole 20 mg / day for 7 AUC increased days only 1.5 times, and C_max – in 1.2 times. T_1/2 in patients with hepatic insufficiency was 12.3 h compared with 2.1 hours in healthy volunteers. Pharmacodynamic response (control gastric pH) in both groups was clinically comparable.

Elderly patients excretion rabeprazole slowed somewhat. Through 7 days after administration of rabeprazole sodium 20 mg / day in these patients AUC was about 2 times, a C_max – on 60% higher as compared with young healthy volunteers. However, signs of accumulation of rabeprazole were noted.

In the case of slow metabolism CYP2C19 after taking rabeprazole 20 mg / day for 7 days increases AUC 1.9 times, a T_1/2 – in 1.6 times compared to the same parameters in “fast” metabolizers, while C_max increases by 40%.

Pariet: testimony

- Duodenal ulcer in the acute phase;

- A stomach ulcer in the acute phase;

- Gastroesophageal reflux disease (GERD): erosive reflux esophagitis (treatment), symptomatic treatment of GERD (ie. NERD - non-erosive reflux disease);

- Zollinger-Ellison Syndrome or other condition, characterized by pathological hypersecretion.

In combination with antibacterial agents:

- For Helicobacter pylori eradication in patients with peptic ulcer or chronic gastritis;

- For the treatment and prevention of recurrence of ulcers in patients with peptic ulcer disease, associated with Helicobacter pylori.

Pariet: dosing regimen

At duodenal ulcer and gastric ulcer in the acute phase It is recommended to take 1 tab. (20 mg) 1 times / day in the morning for 4-6 weeks.

Some patients with acute exacerbation of duodenal ulcer good effect reception 1 time / day 1 tab. by 10 mg.

The majority of patients with duodenal ulcer healing ulcers occur within 4 weeks, but some patients for healing ulcers may require an additional 4-week course of treatment with Pariet^®.

The majority of patients with gastric ulcer healing occurs within 6 weeks, but some patients for healing ulcers may require an additional 6-week course of treatment with Pariet^®.

At treatment of GERD it is recommended to take Pariet^® by 1 tab. (20 mg) 1 times / day for 4-8 weeks.

To maintenance treatment of GERD Pariet^® administered at a dose of 10 mg or 20 mg 1 time / day depending on response to therapy.

To symptomatic treatment of GERD patients without esophagitis Pariet^® administered at a dose of 10 mg 1 times / day for 4 weeks. If the 4 weeks of treatment, the symptoms do not disappear, should conduct an additional examination of the patient.

To treatment of Zollinger-Ellison syndrome and other conditions, characterized by pathological hypersecretion, Dose picked individually. The initial dose is 60 mg / day, then increase the dose, and the drug is prescribed at a dose of 100 mg / day in single or reception 60 mg 2 times / day. For some patients, the fractional drug dosing is preferred. Treatment should continue as clinically necessary. Some patients with Zollinger-Ellison syndrome treatment duration was up to rabeprazole 1 year.

To treatment duodenal ulcer or chronic gastritis, associated with Helicobacter pylori infection, some variants of eradication with appropriate combinations of antibiotics. Recommended treatment duration 7 day of one of the following combinations of drugs:

Pariet^® by 20 mg 2 times / day + Clarithromycin 500 mg 2 times / day and amoxicillin 1 g 2 times / day.

Pariet^® by 20 mg 2 times / day + Clarithromycin 500 mg 2 times / day, and metronidazole 400 mg 2 times / day.

The best results of eradication, exceeding 90%, observed with the combination of the drug Pariet^® with clarithromycin, and amoxicillin.

According to the testimony, requiring dosing 1 time / day, Pariet^® should be taken in the morning before a meal. Established, that any time of the day, audio meal does not affect the activity of the drug. But recommended while taking Pariet Tablets^® It contributes to a better patient compliance.

The tablets should be swallowed whole, without chewing or crushing.

Pariet: side effects

From the digestive system: diarrhea, abdominal pain, flatulence, dry mouth, nausea, vomiting, constipation; rarely – anorexia; in a few cases – increase in liver transaminases.

CNS: headache, asthenia, insomnia, drowsiness, dizziness.

From the hematopoietic system: rarely – thrombocytopenia, neutropenia, leukopenia.

Dermatological reactions: skin rash.

Allergic reactions: rarely – swelling of the face, breathlessness, эritema, bullous rash (reactions disappear after drug withdrawal).

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

Other: effects, whose connection with the drug intake is not installed – backache, flu-like symptoms, myalgia, arthralgia, rarely – decreased appetite, weight gain, depression, blurred vision or taste sensations, stomatitis, increased sweating.

Based on the experience of clinical tests, we can conclude, that Pariet^® generally well tolerated. Side effects are generally mild to moderate and transient in nature are.

Pariet: Contraindications

- Pregnancy;

- Lactation (breast-feeding);

- Hypersensitivity to the drug;

- Hypersensitivity to the substituted benzimidazole.

Pariet: Pregnancy and lactation

Pariet^® is contraindicated in pregnancy and lactation (breast-feeding).

Data on the safety of the drug Pariet^® during pregnancy is not.

IN experimental studies fertility in rats and rabbits revealed no evidence of impaired fertility or fetal development defects, due to rabeprazole; However, in rats in small quantities drug crosses the placental barrier.

Unknown, whether rabeprazole is allocated with breast milk in humans. Appropriate studies in lactating women have not been conducted. At the same time, rabeprazole detected in the milk of lactating rats, therefore, if necessary, use during lactation should stop breastfeeding.

Pariet: Special instructions

Before starting therapy with Pariet^® is necessary to exclude the presence of gastric malignancy, tk. the drug may mask the symptoms and delay the correct diagnosis.

In a special study in patients with mild or moderate hepatic impairment there were no significant differences between the frequency of adverse drug Pariet^® from that of matched by sex and age of healthy individuals, but, Despite this, caution is recommended at the first appointment of the drug Pariet^® patients with severe hepatic impairment.

Patients with impaired renal or hepatic function dose adjustment Pariet^® not required.

Use in Pediatrics

Pariet^® not recommended for children, because at present there is no experience of its use in pediatric patients.

Effects on ability to drive vehicles and management mechanisms

Based on the features of the pharmacodynamics of rabeprazole and its side effect profile is unlikely, that Pariet^® It affects the ability to drive vehicles and management mechanisms. However, in case of drowsiness should avoid these activities.

Pariet: overdose

To date, information about cases of deliberate overdose Pariet^® It has been reported. Taking the drug in doses of up to 80 mg / day was well tolerated.

Treatment: the holding of symptomatic and supportive therapy. No specific antidote. Rabeprazole sodium is well bound to plasma proteins, so poorly removed by dialysis.

Pariet: drug interaction

Pariet^® metabolized by hepatic microsomal isoenzymes of cytochrome P450. Studies have shown, In healthy volunteers rabeprazole not become clinically significant drug interactions with amoxicillin and other drugs, are metabolized by this enzyme system (warfarin, phenytoin, theophylline, diazepam).

Pariet^® It is pronounced and prolonged decline in the production of hydrochloric acid. Therefore, while the use of drugs, absorption of which depends on the pH of the stomach contents, mentioned drug interactions.

In healthy volunteers receiving rabeprazole sodium caused a decrease in the concentration of ketoconazole in the plasma of blood 33% and increasing the minimum concentration of digoxin on 22%. Therefore, while the use of the drug Pariet^® with ketoconazole or digoxin dose is necessary to correct past.

And rabeprazole concentrations of the active metabolite of clarithromycin, while the application increases by 24% and 50% respectively. This increases the efficacy of this combination when Helicobacter pylori eradication.

The study found no drug interactions Pariet^® with liquid antacids. Besides, found no clinically significant drug interactions Pariet^® food.

Studies in vitro human liver microsomes showed, that rabeprazole is metabolized by CYP2C19 and CYP3A4 isoenzymes. Detected, that the expected concentration in plasma rabeprazole does not have any incentive, no inhibitory effect on the metabolism of CYP3A4. These studies also give reason to believe, that rabeprazole has no effect on the metabolism of cyclosporine.

Pariet: terms of dispensing from pharmacies

The drug is released under the prescription.

Pariet: terms and conditions of storage

The drug should be stored out of reach of children at or above 25 ° C; Do not freeze. Shelf life – 2 year.