The tablets are enteric-soluble, film-coated from light green to green with a bluish tinge, round, biconvex; On a cross-section from almost white to light yellow color.
1 tab.
esomeprazole magnesium dihydrate 21.8 mg,
which corresponds to the content of esomeprazole 20 mg
Excipients: low-substituted giprolose (hydroxypropylcellulose) 14 mg, corn pregelatinised corn starch 37.2 mg, colloidal dioxide 2 mg, mannitol 23 mg, sodium stearyl fumarate 2 mg, microcrystalline cellulose 140 mg.
The composition of the film shell: opadray transparent - 8 mg (hypromellose (hydroxypropylmethylcellulose) - 6.4 mg, macrogol (polyethylene glycol) - 1.6 mg);Acrylic-From green-22 mg (methacrylic acid-ethacrylate copolymer (1: 1) - 14.52 mg, silicon colloidal dioxide 0.22 mg, sodium hydrogen carbonate 0.22 mg, sodium lauryl sulfate 0.11 mg, iron oxide yellow 0.154 mg, dye indigo carmine - 0.176 mg, brilliant blue dye - 0.066 mg, talc - 3.63 mg, titanium dioxide - 2.904 mg); triethyl citrate - 2 mg.
7 pcs. - Packings contour mesh (1) - packs cardboard.
7 pcs. - packings contour mesh (2) - packs cardboard.
7 pcs. - packings contour mesh (4) - packs cardboard.
10 pieces. - Packings contour mesh (1) - packs cardboard.
10 pieces. - packings contour mesh (2) - packs cardboard.
10 pieces. - packings contour mesh (4) - packs cardboard.
14 pcs. - Packings contour mesh (1) - packs cardboard.
14 pcs. - packings contour mesh (2) - packs cardboard.
14 pcs. - packings contour mesh (4) - packs cardboard.
The tablets are enteric-soluble, film-coated from light green to green with a bluish tinge, round, biconvex; On a cross-section from almost white to light yellow color.
1 tab.
esomeprazole magnesium dihydrate 43.6 mg,
which corresponds to the content of esomeprazole 40 mg
Excipients: low-substituted giprolose (hydroxypropylcellulose) 28 mg, corn pregelatinised corn starch 74.4 mg, colloidal colloidal 4 mg, mannitol 46 mg, sodium stearyl fumarate 4 mg, microcrystalline cellulose 280 mg.
The composition of the film shell: opadray transparent - 16 mg (hypromellose (hydroxypropylmethylcellulose) - 12.8 mg, macrogol (polyethylene glycol) - 3.2 mg);Acryl-From green - 44 mg (methacrylic acid-ethacrylate copolymer (1: 1) - 29.04 mg, silicon colloidal dioxide 0.44 mg, sodium hydrogen carbonate 0.44 mg, sodium lauryl sulfate 0.22 mg, iron oxide yellow 0.308 mg, dye indigo carmine - 0.352 mg, brilliant blue dye - 0.132 mg, talc - 7.26 mg, titanium dioxide - 5.808 mg); triethyl citrate - 4 mg.
7 pcs. - Packings contour mesh (1) - packs cardboard.
7 pcs. - packings contour mesh (2) - packs cardboard.
7 pcs. - packings contour mesh (4) - packs cardboard.
10 pieces. - Packings contour mesh (1) - packs cardboard.
10 pieces. - packings contour mesh (2) - packs cardboard.
10 pieces. - packings contour mesh (4) - packs cardboard.
14 pcs. - Packings contour mesh (1) - packs cardboard.
14 pcs. - packings contour mesh (2) - packs cardboard.
14 pcs. - packings contour mesh (4) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
PHARMACHOLOGIC EFFECT
Pharmacodynamics
Esomeprazole is the S-isomer of omeprazole and reduces the secretion of hydrochloric acid in the stomach by specifically inhibiting the proton pump in parietal cells of the stomach. S- and R-isomers of omeprazole have similar pharmacodynamic activity.
Mechanism of action
Esomeprazole is a weak base that transforms into an active form in a highly acidic environment of the secretory tubules of the parietal cells of the gastric mucosa and inhibits the proton pump - the enzyme H + / K + -ATPase, with both basal and stimulated hydrochloric acid being inhibited.
Effect on the secretion of hydrochloric acid in the stomach
After oral administration of 20 mg or 40 mg, the effect of esomeprazole develops within 1 hour. With daily intake of the drug for 5 days at a dose of 20 mg 1 time / day, the average Cmax of hydrochloric acid decreases by 90% after pentagastrin stimulation (when measuring the acid concentration through 6-7 hours after taking the drug on the 5th day of therapy).
In patients with GORD and the presence of clinical symptoms after 5 days of daily oral esomeprazole 20 mg or 40 mg, the intragastric pH above 4.0 was maintained for an average of 13 and 17 hours of 24 hours. Against the background of taking esomeprazole at a dose of 20 mg / day, the value of intragastric pH above 4.0 was maintained at least 8, 12 and 16 hours in 76%, 54% and 24% of patients, respectively.
A correlation was found between plasma concentration in the plasma and inhibition of hydrochloric acid secretion (AUC parameter was used to estimate the concentration).
The therapeutic effect achieved by inhibiting the secretion of hydrochloric acid
When taking the drug at a dose of 40 mg, the healing of reflux esophagitis occurs in approximately 78% of patients after 4 weeks of therapy and in 93% of patients after 8 weeks of therapy.
Treatment with esomeprazole at a dose of 20 mg 2 times / day in combination with appropriate antibiotics for one week leads to successful eradication of Helicobacter pylori in approximately 90% of patients.
Patients with uncomplicated peptic ulcer after a weekly eradication course do not need subsequent monotherapy with drugs that reduce the secretion of the glands of the stomach, to treat ulcers and eliminate symptoms.
The efficacy of esomeprazole in bleeding from peptic ulcers confirmed endoscopically is shown.
Other effects associated with inhibition of hydrochloric acid secretion
During treatment with drugs that reduce the secretion of the gland of the stomach, the concentration of gastrin in the plasma increases as a result of a decrease in the secretion of hydrochloric acid. Due to a decrease in the secretion of hydrochloric acid, the concentration of chromogranin A (CgA) increases. An increase in CgA concentration may influence the results of the examinations to identify neuroendocrine tumors. To prevent this effect, it is necessary to temporarily stop taking esomeprazole 5 days before the study of the concentration of CgA.
In patients who received esomeprazole for a long time, there was an increase in the number of enterochromaffin-like cells, probably due to an increase in the concentration of gastrin in the plasma.
In patients taking drugs that reduce the secretion of the glands of the stomach, for a long period of time, the formation of glandular cysts in the stomach is more often noted. These phenomena are caused by physiological changes as a result of pronounced inhibition of the secretion of hydrochloric acid. Cysts are benign and undergo reverse development.
The use of drugs that suppress the secretion of hydrochloric acid in the stomach, incl. inhibitors of the proton pump, accompanied by an increase in the content of the stomach microbial flora, normally present in the gastrointestinal tract. The use of proton pump inhibitors can lead to a slight increase in the risk of infectious diseases of the gastrointestinal tract caused by bacteria of the genus Salmonella spp. and Campylibacter spp. and probably Clostridium difficile in hospitalized patients.
In two comparative studies with ranitidine, esomeprazole showed better efficacy in treating gastric ulcers in patients receiving NSAIDs, including selective COX-2 inhibitors.
PHARMACOKINETICS
Absorption and distribution
Esomeprazole is unstable in an acidic environment, so for oral use, tablets are coated with enteric-coated membranes. In vivo, only a small fraction of esomeprazole is converted to the R-isomer.
Eating slows and reduces absorption of esomeprazole in the stomach, but this does not have a significant effect on the inhibition of hydrochloric acid secretion.
The drug is rapidly absorbed: C max in the plasma is achieved 1-2 hours after ingestion. Absolute bioavailability of esomeprazole after a single dose of 40 mg is 64% and increases to 89% against a daily intake of 1 time / day. For a dose of 20 mg of esomeprazole, these values ​​are 50% and 68%, respectively. V d at an equilibrium concentration in healthy people is approximately 0.22 l / kg body weight. Esomeprazole binds to plasma proteins by 97%.
Metabolism and excretion
Esomeprazole undergoes a metabolism involving isoenzymes of the cytochrome P450 system. The main part is metabolized with the participation of a specific polymorphic isoenzyme CYP2C19,
hydroxylated and demethylated metabolites of esomeprazole. The metabolism of the remaining part is carried out by the isoenzyme CYP3A4, thus forming the sulfo derivative of esomeprazole, which is the main metabolite, determined in plasma.
The parameters given below mainly reflect the nature of pharmacokinetics in patients with increased activity of the isoenzyme CYP2C19.
The total clearance is approximately 17 l / h after a single dose and 9 l / h - after repeated administration. T 1/2 is 1.3 hours with a systematic intake 1 time / day. AUC increases with repeated administration of esomeprazole. A dose-dependent increase in AUC with repeated admission of esomeprazole is non-linear, which is a consequence of a decrease in metabolism during the "first passage" through the liver, and a decrease in systemic clearance, probably caused by inhibition of the isofermite CYP2C19 with esomeprazole and / or its sulfo derivative.
With a daily intake of 1 time / day esomeprazole completely removed from the blood plasma during a break between doses and does not cumulate.
The main metabolites of esomeprazole do not affect the secretion of hydrochloric acid in the stomach. When administered orally, up to 80% of the dose is excreted as metabolites by the kidneys, the other part by the intestine. In urine, less than 1% of unchanged esomeprazole is found.
Peculiarities of pharmacokinetics in some groups of patients
Approximately 2.9 ± 1.5% of the population decreased the activity of the isoenzyme CYP2C19. In such patients, the metabolism of esomeprazole is mainly carried out with the help of the CYP3A4 isoenzyme. With the systematic administration of 40 mg of esomeprazole, once a day, the mean AUC value is 100% higher than the value of this parameter in patients with increased activity of the isoenzyme CYP2C19. Mean plasma C max values ​​in patients with reduced isoenzyme activity were increased by approximately 60%. These features do not affect the dose and method of use of esomeprazole.
In elderly patients (71-80 years) undergoes significant changes.
After a single dose of 40 mg esomeprazole, the average AUC in women is 30% higher than that of men. With daily administration of the drug 1 time / day, there are no differences in pharmacokinetics in men and women. These features do not affect the dose and method of use of esomeprazole.
In patients with hepatic insufficiency of mild to moderate severity, esomeprazole metabolism may be impaired. In patients with severe hepatic insufficiency the metabolic rate is reduced, which leads to an increase in the value of AUC for esomeprazole by a factor of 2.
The study of pharmacokinetics in patients with renal insufficiency was not carried out.
Because the kidneys exclude not the most esomeprazole, but its metabolite, it can be assumed that the metabolism of esomeprazole in patients with renal insufficiency does not change.
In children aged 12-18 years after repeated administration of 20 mg and 40 mg of esomeprazole, the AUC and Tmax values ​​in blood plasma were similar to the values ​​of AUC and T max in adults.
INDICATIONS
Gastroesophageal reflux disease (GERD)
Treatment of erosive reflux esophagitis:
- prolonged maintenance treatment after healing of erosive reflux esophagitis, prevention of relapses;
- symptomatic treatment of GERD.
Stomach ulcer and duodenal ulcer in combination therapy:
- treatment of duodenal ulcer associated with Helicobacter pylori;
- prevention of recurrences of peptic ulcer associated with Helicobacter pylori.
Prolonged acid-suppressing therapy in patients who underwent bleeding from peptic ulcer (after intravenous administration of drugs that reduce the secretion of the glands of the stomach, for the prevention of recurrence)
Patients taking long-term NSAIDs:
- Treatment of gastric ulcer caused by the intake of NSAIDs;
- prophylaxis of gastric and duodenal ulcers caused by the intake of NSAIDs in patients at risk.
Zollinger-Ellison syndrome or other conditions characterized by pathological hypersecretion of the glands of the stomach, incl. idiatic hypersecretion
DOSING MODE
Inside. The tablet should be swallowed whole, not liquid, squeezed with enough water.
Adults and children from the age of 12
Gastroesophageal reflux disease
Treatment of erosive reflux esophagitis: 40 mg 1 time / day for 4 weeks.
An additional 4-week course of treatment is recommended in cases when, after the first course, the healing of esophagitis does not occur or the symptoms persist.
Long-term maintenance treatment after healing of erosive reflux esophagitis, prevention of relapses: 20 mg 1 time / day.
Symptomatic treatment of GERD: 20 mg 1 time / day for patients without esophagitis. If after 4 weeks of treatment the symptoms do not disappear, an additional examination of the patient should be carried out. After eliminating the symptoms, you can go to the regimen of the drug "if necessary" - 20 mg 1 time / day with the resumption of symptoms. For patients taking NSAIDs and those at risk of developing gastric or duodenal ulcers, treatment is not recommended if necessary.
Adults
Stomach ulcer and squamous cell
In the combination therapy for eradication of Helicobacter pylori:
- Treatment of duodenal ulcer associated with Helicobacter pylori: Esomeprazole Canon 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg. All drugs are taken 2 times / day for 1 week;
- prophylaxis of recurrences of peptic ulcer associated with Helicobacter pylori: Esomeprazole Canon 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg. All drugs are taken 2 times / day for 1 week.
Long-acting suppressive therapy in patients after bleeding from peptic ulcer (after IV application of drugs that reduce the secretion of the glands of the stomach, for the prevention of recurrence): Esomeprazole Canon 40 mg 1 time / day for 4 weeks after intravenous administration of drugs that reduce secretion glands of the stomach.
Patients taking long-term NSAIDs
Treatment of stomach ulcers caused by the intake of NSAIDs: Esomeprazole Canon 20 mg 1 time / day; duration of treatment 4-8 weeks.
Prevention of gastric ulcer and duodenal ulcer caused by the intake of NSAIDs: Esomeprazole Canon 20 mg 1 time / day.
Conditions characterized by pathological hypersecretion of the glands of the stomach, incl. Zollinger-Ellison syndrome and idiopathic hypersecretion: therecommended initial dose of the drug Esomeprazole Canon 40 mg 2 times / day. Then the dose is selected individually, the duration of treatment is determined by the clinical picture of the disease. There is an experience of using 80 to 160 mg of esomeprazole per day, when taking the drug more than 80 mg / day, it is recommended to divide the necessary dose into 2 doses.
Kidney failure: dose adjustment of the drug Esomeprazole Canon is not required. However, experience with esomeprazole in patients with severe renal insufficiency is limited, therefore, caution should be exercised when prescribing this patient.
Hepatic failure: with liver failure of mild to moderate severity, dose adjustment is not required. For patients with severe hepatic insufficiency, the maximum daily dose should not exceed 20 mg.
Elderly patients: dosage adjustment is not required.
SIDE EFFECT
Classification of the incidence of adverse events WHO: very often -? 1/10 appointments (> 10%); often - from? 1/100 to <1/10 of appointments (> 1% and <10%);infrequently - from? 1/1000 to <1/100 of prescriptions (> 0.1% and <1%); rarely - from? 1/10000 to <1/1000 appointments (> 0.01% and <0.1%); very rarely - <1/10000 prescriptions (<0.01%); frequency is unknown - can not be estimated from the available data. In each group, undesirable effects are presented in order of decreasing severity.
Disturbances from the nervous system : often - headache; infrequently - drowsiness, insomnia, dizziness, paresthesia; rarely - agitation, confusion, depression; very rarely - aggressive behavior, hallucinations.
Disturbances from the respiratory system: rarely - bronchospasm.
Disorders from the digestive system: often - abdominal pain, diarrhea, flatulence, nausea, vomiting, constipation; infrequent - dry mouth, increased activity of "liver" enzymes; rarely - stomatitis, candidiasis GIT, hepatitis (with-jaundice or without); very rarely liver failure, hepatic encephalopathy in patients with a history of liver disease, microscopic colitis.
Disorders from the kidneys and urinary tract: very rarely - interstitial nephritis; frequency unknown - renal failure.
Disorders from the reproductive system: very rarely - gynecomastia.
Disorders from the musculoskeletal system: rarely - arthralgia, myalgia; very rarely - muscle weakness; frequency is unknown - fractures of the neck of the thigh, bones of the wrist, vertebrae.
Disturbances from the skin: infrequent - itching, rashes, hives, dermatitis, peripheral edema; rarely - alopecia, photosensitivity, malaise, increased sweating; very rarely - Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.
Disorders from the hematopoiesis: rarely - leukopenia, thrombocytopenia; very rarely - agranulocytosis, pancytopenia.
Disorders from the sensory organ: infrequently - blurred vision; rarely - a taste disorder.
Allergic reactions: rarely - hypersensitivity reactions (eg, fever, angioedema, anaphylactic reaction / anaphylactic shock).
Laboratory and instrumental data: rarely - hyponatremia; very rarely - hypomagnesemia, hypocalcemia due to severe hypomagnesemia, hypokalemia due to severe hypomagnesemia.
CONTRAINDICATIONS
- hypersensitivity to esomeprazole, substituted benzimidazoles or other components of the drug;
- Children under 12 years of age (due to the lack of data on the effectiveness and safety of the drug in this group of patients);
- Children's age from 12 to 18 years for all indications, except for GERD;
- simultaneous reception with atazanavir and nelfinavir.
Carefully
Severe renal failure (application experience is limited).
PREGNANCY AND LACTATION
At present, there is insufficient data on the use of esomeprazole during pregnancy. Epidemiological studies esomeprazole constituting ratsematicheskuyu mixture showed absence foetotoxic actions or fetal developmental disorders. In animal studies did not reveal any direct or indirect adverse effects on the developing embryo or fetus, as in the introduction of esomeprazole and when administered ratsematicheskoy mixture. Prescribed the drug to pregnant women should only if the expected benefit to the mother outweighs the potential risk to the fetus.
It is not known whether esomeprazole with breast milk, so the drug should not be used during breastfeeding is highlighted.
APPLICATION FOR FUNCTIONS OF THE LIVER
Precautions apply to patients with severe renal failure (application experience limited) correction dose is not required Canon esomeprazole.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Patients with liver failure mild or moderate dose adjustment is required.
Patients with severe hepatic insufficiency maximum daily dose should not exceed 20 mg.
APPLICATION FOR CHILDREN
Do not use this drug to children under the age of 12 years (due to lack of data on efficacy and safety of the drug in this patient group).
Do not use this drug to children between the ages of 12 to 18 years for all indications other than GERD.
APPLICATION IN ELDERLY PATIENTS
elderly patients correction dose is not required.
SPECIAL INSTRUCTIONS
If any alarming symptoms (e.g., such as a significant spontaneous loss of body weight, repeated vomiting, dysphagia, vomiting with blood or melena), and in the presence of gastric ulcers (or suspected stomach ulcer) should exclude the presence of malignancy because esomeprazole treatment can lead to smoothing of symptoms and delay diagnosis. The patients taking the drug for a long period (more particularly years) should be under regular supervision. Patients taking esomeprazole "if necessary" should be instructed to contact their physician if symptoms change in character. Taking into account the fluctuations in the concentration of esomeprazole in the plasma in the appointment of therapy "if necessary",should take into account the interaction of the drug with other drugs (see. the section "Interaction with other drugs and other types of drug interactions").
In the application of esomeprazole for eradication of Helicobacter pylori should be considered the possibility of drug interactions for all components of the triple therapy. Clarithromycin is a potent inhibitor of isozyme CYP3A4, so when applying eradication therapy for patients taking other drugs metabolized with isoenzyme CYP3A4 (e.g., cisapride), must take into account possible interactions and contraindications clarithromycin with these drugs.
In the application of the proton pump inhibitor, especially when used in high doses and for prolonged periods (over 1 year) possible risk of hip fracture, vertebral and wrist bones (especially in the elderly). It is also noted the formation of cysts in the glandular stomach, decrease absorption of vitamin B12, hypomagnesemia development.
Impact on the ability to drive vehicles and mechanisms
In the period of treatment can be dizziness, blurred vision and drowsiness, so use caution when driving and occupation of other potentially hazardous activities that require high concentration and psychomotor speed reactions.
OVERDOSE
Currently, cases of overdose of the drug esomeprazole are described very rarely. Oral administration of a dose of esomeprazole 280 mg accompanied by general weakness and symptoms of the digestive tract. Single dose of 80 mg of esomeprazole did not cause any adverse effects.
Treatment: a specific antidote is unknown. Hemodialysis is ineffective. In case of overdose, it is recommended the holding of symptomatic and general supportive therapy.
DRUG INTERACTION
Effect of esomeprazole on the pharmacokinetics of other drugs
hydrochloric acid Reduced secretion in the stomach during the treatment with esomeprazole and other proton pump inhibitors can cause a change in the absorption of drugs, absorption of which depends on the acidity of the medium. Like other drugs and antacids, reducing gastric acidity, esomeprazole use can lead to decreased absorption of ketoconazole, itraconazole and erlotinib, and enhance absorption of drugs such as digoxin.
Simultaneous treatment with esomeprazole 20 mg 1 time / day and digoxin increases the bioavailability of digoxin in 10% (bioavailability of digoxin was increased by up to 30% in two of 10 patients).
It is known about the interaction of esomeprazole with some antiretroviral drugs. Mechanisms and clinical implications of these interactions are not always known. The increase in the pH value during therapy with esomeprazole may interfere with the absorption of antiretroviral drugs. It is also possible for the interaction CUR2S19 isoenzyme level.
The joint appointment of esomeprazole and some antiretroviral drugs, such as atazanavir and nelfinavir, against the background of esomeprazole therapy, there is a decrease in their serum concentrations. Therefore, their simultaneous use is not recommended.
The combined use of esomeprazole 40 mg 1 time / day, and 300 mg of atazanavir / ritonavir 100 mg to healthy volunteers resulted in a significant reduction of atazanavir bioavailability (AUC, and C max and Cmin decreased by approximately 75%). Increasing the dose of atazanavir to 400 mg of an offset impact the bioavailability of esomeprazole atazanavir.
With simultaneous application of esomeprazole saquinavir and saquinavir increase was observed serum concentration; when used with certain other anti-retroviral drugs, their concentration was not changed. Given similar pharmacokinetic and pharmacodynamic properties of omeprazole and esomeprazole, combined use of esomeprazole with antiretroviral drugs such as nelfinavir and atazanavir is not recommended.
Esomeprazole inhibits isozyme CYP2C19 - primary enzyme involved in its metabolism. Accordingly, the combined use of esomeprazole with other drugs, in which metabolism is involved isoenzyme CYP2C19, such as diazepam, citalopram, imipramine, clomipramine, phenytoin et al., May lead to increased concentrations of these drugs in the plasma, which in turn may require dose reduction. This cooperation is especially important to remember when administering the drug esomeprazole Canon in the "if necessary". When co-administered 30 mg of esomeprazole and diazepam which is a substrate for the isoenzyme CYP2C19, there is a decrease in clearance of 45% of diazepam.
Purpose of esomeprazole 40 mg resulted in increased residual concentration of phenytoin in patients with epilepsy is 13%. In this connection, it is recommended to monitor phenytoin plasma concentration at the beginning of treatment with esomeprazole and its abolition.
Simultaneous application of esomeprazole 40mg increases the phenytoin concentration in the blood plasma of patsentov epilepsy 13%.
It is recommended to monitor fenitonina plasma concentration at the beginning of therapy with esomeprazole and its abolition.
In applying esomeprazole 40mg 1 time / day and increased AUC T max voriconazole (substrate isoenzyme CYP2C19) at the 15% and 41% respectively.
Joint warfarin and 40 mg of esomeprazole does not change the time of coagulation in patients receiving long-term warfarin. However, several reported cases of clinically significant increase in the INR index in the combined use of warfarin and esomeprazole. It is recommended to monitor the INR in the beginning and at the end of the joint use of esomeprazole and warfarin or other coumarin derivatives.
Co-administration of cisapride with 40 mg of esomeprazole leads to increased pharmacokinetic parameters of cisapride in healthy volunteers: AUC - 18% T 1/226% for one of the active metabolites tsitostazola increase was 29% and 69% respectively. Simultaneous application of esomeprazole 40mg with cisapride leads to increased pharmacokinetic parameters of cisapride values in healthy volunteers: AUC by 32% and T 1/2 of 31%, but the C max while not significantly changed.
Slight prolongation of the interval QT, which was observed with monotherapy cisapride, adding esomeprazole not increased.
Some patients mentioned increased serum concentrations of methotrexate on the background of the simultaneous use of proton pump inhibitors. At higher doses of methotrexate should consider temporal cancellation of esomeprazole.
Esomeprazole does not cause clinically significant changes in the pharmacokinetics of amoxicillin and quinidine.
Studies to evaluate the short-term joint use of esomeprazole and naproxen or rofecoxib did not reveal any clinically significant pharmacokinetic interaction.
Simultaneous use of short esomeprazole and naproxen or rofecoxib showed no clinically significant pharmacokinetic interactions.
In a clinical study we investigated the interaction with clopidogrel (300 mg loading dose, followed by 75 mg / day) with esomeprazole (80 mg) in one stage, at the same time for 5 days. Active thiol metabolite (active metabolite) Clopidogrel was reduced by 46% (1 st day of therapy) and 42% (5 th day of therapy), while taking clopidogrel and omeprazole at one time. When receiving clopidogrel and esomeprazole in one time mean inhibition of platelet aggregation (IRA) was reduced by 47% (within 24 hours of therapy) and 30% (5 th day of therapy).
According to the results of another study: the application of esomeprazole with clopidogrel is not simultaneously, at different times, has no inhibitory effect on the isoenzyme CYP2C19. The studies have been reported conflicting data from clinical manifestations of interaction with clopidogrel on cardiovascular system.
While the use of tacrolimus may increase serum concentrations of tacrolimus.
Effect of drugs on the pharmacokinetics of esomeprazole
in the metabolism of esomeprazole participate isozymes CYP2C19 and CYP3A4.
The combined use of esomeprazole with clarithromycin (500 mg, 2 times / day), which inhibits isozyme AUC values esomeprazole 2 times.
The combined use of esomeprazole and a combined inhibitor of isozyme CYP3A4 and CYP2C19, e.g., voriconazole may lead to more than 2-fold increase in the AUC values for esomeprazole. Typically, in such cases is not required correction dose of esomeprazole.
Drugs inducing isozymes CYP2C19 and CYP3A4, such as rifampicin and preparations Hypericum perforatum, while the use of esomeprazole can lead to a decrease in the concentration of esomeprazole in plasma by accelerating the metabolism of esomeprazole.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The preparation should be stored in a dry place, protected from light and the reach of children 25 В° C. Shelf life - 2 years.
Do not use after the expiration date.
