Pariet pills 20mg №28

Mechanism of action

Anti-ulcer drug. H inhibitor⁺-TO⁺-ATP-ase (proton pump). The active substance of the drug - Rabeprazole sodium - is a weak base, which, when used in any doses, quickly accumulates in the acidic environment of the parietal cells and, turning into the active sulfenamide group, interacts with proton pump cysteines.
The mechanism of action is associated with inhibition of the enzyme H⁺-TO⁺-ATP-ases in the parietal cells of the stomach, which leads to blocking of the final stage of formation of hydrochloric acid. This action is dose-dependent and leads to inhibition of both basal and stimulated secretion of hydrochloric acid, regardless of the nature of the stimulus.
After ingestion in a dose of 20 mg, the effect of the drug develops within 1 hour and reaches a maximum after 2-4 hours. The depression of basal and food-stimulated acid secretion 23 hours after the first dose is 62% and 82%, respectively, and the duration of action reaches 48 h. The inhibitory effect is somewhat enhanced by the daily intake of the drug; stable depression of secretion is achieved 3 days after the start of administration. After discontinuation of the drug, secretory activity is restored in 2-3 days.
When taking the drug in a dose of 10 mg or 20 mg 1 time / day in the first 4-8 weeks there is an increase in the concentration of gastrin in the blood serum, which returns to its initial level within 1-2 weeks after stopping the treatment.
Taking the drug at a dose of 20 mg / day for 2 weeks has no effect on thyroid function, carbohydrate metabolism, blood concentrations of parathyroid hormone, cortisol, estrogen, testosterone, prolactin, cholecystokinin, secretin, glucagon, FSH, LH, STG, renin, aldosterone.

Suction
Thanks to a special dosage form, the absorption of rabeprazole sodium occurs in the intestine. After taking a dose of 20 mg C_maxreached in 3.5 hours. Changes C_max and AUC are linear (in the dose range from 10 to 40 mg). Absolute bioavailability after a 20 mg dose is about 52% due to the “first pass” effect through the liver. The bioavailability of rabeprazole does not increase with repeated use.
Eating and taking the drug during the day do not affect the absorption of rabeprazole.
Distribution
Plasma protein binding is 97%.
Metabolism
Rabeprazole sodium is subject to the "first pass" effect. Metabolized in the liver by cytochrome P₄₅₀.
Rabeprazole sodium is biotransformed to form the major metabolites — thioether and carboxylic acid, and minor metabolites (sulfone, dimethyl thioether, and mercaptopuric acid conjugate), which are present in low concentrations.
Removal
In healthy volunteers T_1/2 makes about 1 h (0.7-1.5 h), the total clearance makes 283 ± 98 ml / min.
After a single ingestion of 20 mg of labeled¹⁴C rabeprazole sodium was not observed excretion of the active substance in unchanged form.
Approximately 90% of the indicated dose is excreted in the urine mainly in the form of two metabolites: a mercaptopuric acid conjugate and a carboxylic acid. In addition, another 2 unidentified metabolites were found in toxicological studies in laboratory animals. The rest is excreted with feces.
Pharmacokinetics in special clinical situations
No significant differences in pharmacokinetic parameters, depending on gender, were noted.
In patients with stable terminal stage of chronic renal failure in need of hemodialysis (QA less than 5 ml / min / 1.73 m²), the distribution of rabeprazole sodium is close to that of healthy volunteers. AUC and C_max in this category of patients were 35% lower than in healthy volunteers. Average t_1/2rabeprazole was 0.82 hours in healthy volunteers, 0.95 hours in patients during hemodialysis, and 3.6 hours after hemodialysis. In renal diseases, clearance of rabeprazole in patients on hemodialysis was approximately 2 times higher than in healthy volunteers.
In patients with chronic or moderate hepatic insufficiency, after a single dose of rabeprazole, AUC increased 2 times, T_1/2- 2-3 times in comparison with healthy volunteers. However, after taking rabeprazole at 20 mg / day for 7 days, the AUC increased only 1.5 times, C_max - 1.2 times. T_1/2 in patients with hepatic impairment was 12.3 h compared with 2.1 h in healthy volunteers.The pharmacodynamic response (control of the pH of the stomach contents) in both groups was clinically comparable.
In elderly patients, the clearance of rabeprazole is somewhat slow. 7 days after taking rabeprazole sodium at 20 mg / day for this category of patients, the AUC was about 2 times higher, and C_max 60% higher compared to young healthy volunteers. However, the accumulation of rabeprazole was not observed.
In the case of a slow metabolism of CYP2C19 after taking rabeprazole at 20 mg / day for 7 days AUC and T_1/2 were 1.9 and 1.6, respectively, with extensive metabolism, while C_maxincreased only by 40%.

Indications and usage

- peptic ulcer of the stomach and duodenum in the acute phase;
- gastric ulcer and duodenal ulcer associated with Helicobacter pylori;
- Gastroesophageal reflux.

atgastric ulcer and duodenal ulcer in the acute phase appoint 20 mg 1 time / day.
Atduodenal ulcer in some cases, appoint 10 mg 1 time / day.
The duration of therapy forduodenal ulceraverages 4 weeks. However, in those patients in whom the ulcer did not completely scar, the treatment should be continued for another 4 weeks.
The duration of therapy forgastric ulcer averages 6 weeks. In cases where complete scarring of the ulcer did not occur, treatment should be continued for another 6 weeks.
Atgastroesophageal reflux the drug is prescribed 20 mg 1 time per day for 4-8 weeks.Maintenance dose is 10 mg or 20 mg 1 time / day.
Fortreatment of gastric ulcer and duodenal ulcer or chronic gastritis associated with Helicobacter pylori, use several options for eradication using a combination of antibiotics. The recommended duration of treatment is 7 days using one of the following regimens.
1) Parite administered 20 mg 2 times / day + Clarithromycin 500 mg 2 times / day + Amoxicillin 1 g 2 times / day;
2) Pariet 20 mg 2 times / day + clarithromycin 500 mg 2 times / day + Metronidazole 400 mg 2 times / day.
It has been established that the eradication of Helicobacter pylori, carried out according to one of these schemes, leads to the healing of a gastric or duodenal ulcer without further anti-ulcer therapy.
According to indications that require taking the drug 1 time / day, Pariet should be taken in the morning before meals.
For eradication of Helicobacter pylori when prescribed in combination with Pariet antibiotics should be taken 2 times / day.
Tablets should be swallowed whole, without chewing.

Adverse reactions

Gastrointestinal:> = 5% - diarrhea, nausea; 2-5% - abdominal pain, vomiting, flatulence, constipation; <= 1% - dry mouth, dyspepsia, belching; in rare cases - anorexia, gastritis, stomatitis, increased activity of hepatic transaminases.
From the side of the central nervous system: > = 5% - headache; 2-5% - asthenia, dizziness, insomnia; <= 1% - nervousness, drowsiness; in rare cases - depression, visual disturbances and taste sensations.
Respiratory: 2-5% - rhinitis, pharyngitis, cough; less than 1% - sinusitis, bronchitis.
Allergic reactions: <= 1% - skin rash; in isolated cases - itching.
Other: 2-5% - back pain, flu-like syndrome; <= 1% - myalgia, chest pain, chills, calf muscle cramps, urinary tract infection, arthralgia, fever; in isolated cases - an increase in body weight, increased sweating, leukocytosis.
In most cases, it was impossible to establish a connection between taking the drug and the appearance of one or another effect, with the exception of headache, diarrhea, abdominal pain, asthenia, flatulence, skin rash, dry mouth.

- pregnancy;
- lactation (breastfeeding);
- hypersensitivity to rabeprazole sodium or substituted benzimidazoles.

Pariet is contraindicated for use in pregnancy, due to the lack of reliable clinical data confirming the safety of the drug during this period.
If necessary, the use of Pariet during lactation should decide on the termination of breastfeeding (due to the lack of data on the allocation of rabeprazole sodium in breast milk).
ATexperimental studiesIt was established that rabeprazole sodium in insignificant amounts penetrates the placental barrier, however, no fertility disorders or fetal developmental defects were noted. It is also established that rabeprazole is excreted in milk of lactating rats.

Before starting Pariet therapy, it is necessary to exclude malignant tumors of the stomach, since taking the drug may mask the symptoms and delay the correct diagnosis of the tumor.
Patients with impaired liver function and / or kidney dose adjustment is not required, but caution is advised when prescribing the first dose of Pariet in patients with severely impaired liver function.
The study of biopsy specimens of the bottom and antrum of the stomach in patients who took rabeprazole for 8 weeks showed no changes in the histology of enterochroma-like cells, increased gastritis, increased frequency of atrophic gastritis, the development of intestinal metaplasia, and the spread of H.pylori infection.
Use in pediatrics
It is not recommended to prescribe pariet to children, because at present there is no experience of its use in pediatric practice.
The results of experimental studies
In studies conducted on laboratory animals, the carcinogenic effect of the drug was not established, while mutagenicity studies revealed ambiguous results. Tests on lymphoma cells in mice were positive, but the in vivo micronucleus test and the in vivo and in vitro DNA repair tests were negative.

Currently, cases of overdose of the drug Pariet were reported. Taking the drug at a dose of 80 mg / day did not lead to the development of any life-threatening symptoms.
Treatment: in case of accidental use of the drug in high doses, symptomatic therapy is carried out. There is no specific antidote. Rabeprazole sodium is highly bound to plasma proteins, and therefore poorly removed during dialysis.

Parite is metabolized by cytochrome P microsomal liver enzymes.₄₅₀ 2C19 and 3A. Studies on healthy volunteers have shown that rabeprazole sodium does not enter into clinically significant drug interactions with other drugs that are metabolized by the same enzymes (warfarin, phenytoin, theophylline, diazepam).
Pariet causes a pronounced and prolonged decrease in the formation of hydrochloric acid. Therefore, with simultaneous use with drugs, the absorption of which depends on the pH of the contents of the stomach, drug interaction was noted. In healthy volunteers, taking rabeprazole sodium caused a decrease in plasma Ketoconazole concentrations by 33% and an increase in the minimum concentrations of Digoxin by 22%. Therefore, while applying Pariet with ketoconazole or digoxin, it is necessary to adjust the dose of the latter.
The studies did not reveal the interaction of Pariet with liquid antacids.
With the simultaneous use of rabeprazole usually does not affect the metabolism of cyclosporine, because at the observed concentrations of rabeprazole sodium did not affect the metabolism of CYP3A4 .

The drug should be stored at a temperature not higher than 25 ° C; Do not refrigerate. Shelf life - 2 years.
Pharmacy sales terms
The drug is available on prescription.