Description of the active substance:
This information is a reference and it is not enough that the drug has been prescribed by a doctor ..
PHARMACHOLOGIC EFFECT
H + -K + -ATPase inhibitor, dextrorotatory isomer of omeprazole. Reduces the secretion of hydrochloric acid in the stomach by specifically inhibiting the proton pump in parietal cells. Being a weak base and passing into the active form in the acidic environment of the secretory tubules of parietal cells of the gastric mucosa, it activates and inhibits the proton pump - the enzyme H + -K + -ATP-ase. Inhibits both basal and stimulated secretion of hydrochloric (hydrochloric) acid. The action occurs 1 hour after oral administration of 20 mg or 40 mg. With daily use for 5 days at a dose of 20 mg 1 time / day, the average maximum concentration of hydrochloric acid after stimulation with pentagastrin is reduced by 90%.
PHARMACOKINETICS
Unstable in an acidic environment. In vivo, only a small fraction of esomeprazole is converted to the R-isomer. After oral administration, it is rapidly absorbed from the digestive tract. C max in blood plasma is achieved after 1-2 hours. Absolute bioavailability with repeated admission in a dose of 20 mg 1 time / day - 89%. V d - 0.22 l / kg. Binding to plasma proteins - 97%. It is completely metabolized with the participation of cytochrome P450 isoenzymes. The main part is metabolized with the participation of CYP2C19 with the formation of hydroxy- and demethylated metabolites of esomeprazole. The metabolism of the remainder is carried out by another isoenzyme CYP3A4; This produces a sulfo derivative of esomeprazole, which is the main metabolite, determined in plasma. All metabolites are pharmacologically inactive. In patients with active isozyme CYP2C19 (patients with active metabolism), the systemic clearance is 17 l / h after a single dose and 9 l / h after repeated administration. T 1/2 - 1.3 hours with a systematic intake in the dosing regimen 1 time / day. AUC increases with the background of repeated administration (non-linear dose dependence and AUC in a systematic admission, which is a consequence of reduced metabolism during the "first passage" through the liver, and a decrease in systemic clearance caused by inhibition of the enzyme CYP2C19 with esomeprazole and / or its sulfo-containing metabolite). Do not cumulate. Output up to 80% of the dose in the form of metabolites by the kidneys (less than 1% - unchanged), the rest - with bile.
In patients with inactive metabolism (1-2%), esomeprazole metabolism is mainly carried out with the participation of the CYP3A4 isoenzyme. When administered systematically at a dose of 40 mg 1 time / day, the mean AUC is 100% greater than the value of this parameter in patients with active metabolism. Mean C max values ​​in plasma in patients with inactive metabolism were increased by approximately 60%.
With severe hepatic insufficiency, the metabolic rate is reduced, which is accompanied by an increase in AUC by 2 times.
INDICATIONS
Gastroesophageal reflux disease: erosive reflux-esophagitis (treatment), prevention of relapses in patients with cured esophagitis, symptomatic treatment of GERD.
In the combination therapy: Helicobacter pylori eradication, duodenal ulcer associated with Helicobacter pylori, prevention of recurrence of peptic ulcers in patients with peptic ulcer associated with Helicobacter pylori.
DOSING MODE
Is taken internally. The dose is 20-40 mg 1 time / day. Duration of admission depends on the indications, treatment regimen, effectiveness.
In severe hepatic insufficiency, the maximum dose is 20 mg / day.
SIDE EFFECT
Often: headache, abdominal pain, diarrhea, flatulence, nausea, vomiting, constipation.
Rarely: dermatitis, itching, hives, dizziness, dry mouth.
CONTRAINDICATIONS
Lactation period, hypersensitivity to esomepromazole.
PREGNANCY AND LACTATION
Data on the safety of esomeprazole in pregnancy are absent. The use is possible in cases where the expected benefit of therapy for the mother exceeds the possible risk to the fetus.
In experimental animal studies, there was no direct or indirect adverse effect on the development of the embryo or fetus. The introduction of racemic substance also did not have any negative impact on animals during pregnancy, during childbirth, and also during postnatal development.
Contraindicated during lactation.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
In severe hepatic insufficiency, the maximum dose is 20 mg / day.
SPECIAL INSTRUCTIONS
In the presence of such symptoms as significant spontaneous weight loss, frequent vomiting, dysphagia, vomiting with blood or melena, and if there are (or suspected) gastric ulcers, the possibility of malignant growth should be excluded, since the treatment with esomeprazole may lead to a smoothing of the symptoms and, thus , delay the setting of the correct diagnosis.
With prolonged therapy, the patient should be monitored regularly.
During treatment with proton pump inhibitors, the level of gastrin in the plasma is increased as a result of reduced intragastric secretion of hydrochloric acid. In patients taking proton pump inhibitors for a long time, the formation of glandular cysts in the stomach is more often noted. These phenomena are due to physiological changes due to inhibition of the secretion of hydrochloric acid.
DRUG INTERACTION
It is believed that with simultaneous use, it is possible to increase concentrations in the blood plasma and enhance the effects of imipramine, clomipramine, citalopram.
It is believed that with simultaneous use, it is possible to reduce the concentrations in the blood plasma and the clinical efficacy of itraconazole and ketoconazole.
With simultaneous use with clarithromycin, the case of a significant increase in AUC of esomeprazole has been described due to the inhibition of its metabolism under the influence of clarithromycin.
With simultaneous use, it is possible to increase the concentrations in the blood plasma of diazepam and phenytoin, which, apparently, has no clinical significance.
