Emanera - instructions for use, dose, side effects, contraindications

Opadry II White 85F28751 ** 23,440 mg, magnesium hydroxycarbonate (magnesium carbonate heavy) 3,000 mg, methacrylic acid and ethyl acrylate copolymer [1: 1], dispersion 30% *** 127,490 mg, talc 11,925 mg, macrogol 6,000 3,825 mg, titanium dioxide (E 171) 3,825 mg, polysorbate - 80 1,720 mg

Gelatin capsule 48,000 mg Composition of empty gelatin capsules: Body capsules:

Pig iron red oxide (E 172) 0.014 mg, titanium dioxide (E 171) 0.406 mg, gelatin **** 28.380 mg Cover capsules:

Pig iron red oxide (E 172) 0.010 mg, titanium dioxide (E 171) 0.271 mg, gelatin **** 18.920 mg

* Sugar loaves contain sucrose and

molasses starch.

** Opadrai II White 85F28751 represents

a mixture of:

Polyvinyl alcohol 9.376 mg, titanium

dioxide (E 171) 5.860 mg, macrogol - 3000

4.735 mg, talc 3.469 mg

***Dispersion Eudragit L30D contains

in addition to methacrylic acid,

ethyl acrylate copolymer and water, also

sodium lauryl sulfate (0.7% of

solid in the dispersion) and

polysorbate-80 (2.3 % for the solid

substance in dispersion) as

emulsifiers.

**** Contains an average of 14.5% water

(loss in mass when dried).

1 capsule, enteric, 40 mg

contains:

Pellet core:

Active substance: 40 mg

Esomeprazole magnesium 41.290 mg (which

is equivalent to esomeprazole 40,000 mg)

Excipients:

Sugar flour * 71,160 mg, povidone K30

15,000 mg, sodium lauryl sulfate 1,800 mg

Pellet shell:

** Opadrai II White 85F28751 ** 46.880 mg,

magnesium hydroxycarbonate (magnesium carbonate

heavy) 6,000 mg, methacrylic

acid and ethyl acrylate copolymer [1: 1],

dispersion 30% *** 254.980 mg, talc 23.850

mg, macrogol - 6000 7.650 mg, titanium 6.938 mg *** Dispersion

gelatin capsules: Body capsules:

Iron coloring red oxide (E 172) 0.114 mg, titanium dioxide (E 171) 0.458 mg, gelatin **** 45.028 mg Cover capsules:

The iron dye red oxide (E 172) 0.076 mg, titanium dioxide (E 171) 0.305 mg, gelatin **** 30.019 mg

Sugars contain sucrose and starch treacle.

** Opadrai II White 85F28751 is a mixture of:

Polyvinyl alcohol 18.752 mg, titanium dioxide (E 171) 11.720 mg, macrogol - 3000

9,470 mg, talc 6.938 mg

*** Dispersion Eudragit L30D contains besides methacrylic acid, ethyl acrylate copolymer and water, also sodium lauryl sulfate (0.7% for the solid in the dispersion) and polysorbate-80 (2.3% for the solid in the dispersion) as emulsifiers.

**** Contains an average of 14.5% water (loss in mass when dried).

Description:

Capsules 20 mg:

Capsules No. 3. Housing and cap light pink color. Contents of the capsule: pellets from white to almost white.

Capsules 40 mg:

Capsule number 1. Case and cap capsule pink. Contents of the capsule: pellets Capsules of light pink color. Contents of the capsule: pellets from white to almost white.

Capsules 40 mg:

Capsules № 1. Body and cap

capsules from pink to pink with a slightish gray tinge colors.Contents of the capsule: pellets from white to almost white.

Pharmacotherapeutic group:glands of the stomach secretion-lowering agent - proton pump inhibitor

ATX: & nbsp

Esomeprazole

Pharmacodynamics:

Esomeprazole is S-isomer of omeprazole and suppresses the secretion of hydrochloric acid in the stomach due to a specific and directed mechanism of action. Specifically inhibits the proton pump of parietal cells. Both isomers of omeprazole, R- and S-, have similar pharmacodynamic activity. Mechanism of action

Esomeprazole is a weak base, so it accumulates and becomes active in conditions of a highly acidic environment of the secretory tubules of the parietal cells of the gastric mucosa, where it suppresses the activity of the enzyme H⁺/TO⁺-ATPase. Suppresses both basal and stimulated secretion of hydrochloric acid.

Effect on secretion of acid in the stomach The effect develops within 1 hour after ingestion of 20 mg or 40 mg

esomeprazole. At repeated admission of 20 mg of esomeprazole once a day for 5 days, the average peak concentration of hydrochloric acid after pentagastrin stimulation is reduced by 90% (on day 5 of therapy 6-7 hours after taking the drug).

In patients with gastroesophageal reflux disease (GERD) and the presence of clinical symptoms after a daily intake of esomeprazole at a dose of 20 mg or 40 mg in for 5 days, the pH level of stomach contents above 4.0 was maintained, on average, for 13 and 17 hours, respectively. The proportion of patients taking esomeprazole in a dose of 20 mg / day, in which the pH of the gastric contents exceeded 4.0 for 8, 12 and 16 hours, respectively, were 76%, 54% and 24%, and for esomeprazole 40 mg / day 97%, 92 % and 56%.

The degree of suppression of acid secretion with esomeprazole is directly proportional to the area under the concentration-time curve.

The therapeutic effect achieved by suppressing acid secretion The healing of reflux esophagitis, when taking esomeprazole at a dose of 40 mg, occurs in approximately 78% of patients after 4 weeks and in 93% of patients after 8 weeks of therapy.

Treatment with esomeprazole at a dose of 20 mg twice a day for 1 week in combination with

leads to successful eradication

Helicobacter pylori 90% of patients.

With an uncomplicated peptic ulcer after eradication therapy

(duration from 7 to 10-14 days) does not require continuation of monotherapy with antisecretory drugs for ulcer healing and elimination of symptoms. Other effects associated with the suppression of acid secretion

Against the background of therapy with antisecretory drugs, the level of gastrin in blood serum increases in response to a decrease in acid secretion.

In some patients, after prolonged therapy with esomeprazole, an increase in the number

enterochromaffin-like (ELC) cells, probably associated with an increase in the level gastrin in the blood plasma.

With prolonged intake of antisecretory drugs, there was a slight increase in the frequency of formation of the glandular cysts of the stomach. These changes are due to physiological changes in

the result of prolonged suppression

acid secretion. Cysts

They are benign and of a reversible nature.

Reduction of the acidity of gastric contents against the background of antisecretory medication is accompanied in the stomach present in the gastrointestinal tract (GIT) in the norm. Therapy with proton pump inhibitors can lead to an insignificant increase in the risk of infectious diseases of the gastrointestinal tract, for example caused by bacteria of the genus Salmonella and Campylobacter spp.

Esomeprazole is more effective in healing gastric ulcers in patients who have used nonsteroidal anti-inflammatory drugs

(NSAIDs), including selective inhibitors of COX-2 in comparison with ranitidine.

High efficacy of esomeprazole in the prevention of gastric and duodenal ulcers in patients taking NSAIDs has been noted (for patients older than

60 years old and / or with a peptic ulcer in anamnesis), in including selective inhibitors of COX-2.

Pharmacokinetics:

Suction and distribution Esomeprazole is unstable in an acidic medium, therefore it is taken orally in the form of enteric capsules containing pellets of the preparation, the shell of which is also resistant to the action of gastric juice. In conditions in vivo a small fraction of esomeprazole passes into Risomer. Esomeprazole quickly absorbed, reaching blood approximately 1-2 hours after ingestion. Absolute bioavailability is 64% after taking a single dose of 40 mg, which rises to 89% with daily esomeprazole taking once daily. Bioavailability for esomeprazole at a dose of 20 mg is 50% and 68%, respectively. The volume of distribution in the equilibrium state in healthy volunteers is approximately 0.22 l / kg body weight. Connection with blood plasma proteins - 97%.

Eating slows and reduces absorption of esomeprazole, while not having a significant clinical

values.

Metabolism and excretion Esomeprazole is completely metabolized with the participation of the cytochrome P450 isoenzyme system in the liver. The most part is metabolized with participation

polymorphic isoenzyme CYP2C19, which is responsible for the formation of hydroxy- and demethylated metabolites.

The remainder of esomeprazole

is metabolized by isoenzyme CYP3A4, responsible for the formation of sulfone esomeprazole, the main metabolite in plasma blood.

The total plasma clearance after taking a single dose is approximately 17 l / h and 9 l / h - after multiple intake. The half-life (T_1/2 ) is 1.3

maximum concentrations in the blood plasma approximately 1-2 hours after ingestion. Absolute bioavailability is 64% after taking a single dose of 40 mg, which rises to 89% with daily esomeprazole taking once daily. Bioavailability for esomeprazole at a dose of 20 mg is 50% and 68%, respectively. Size

distribution in the equilibrium state in healthy volunteers is approximately 0.22 l / kg body weight.Connection with blood plasma proteins - 97%.

Eating slows and reduces absorption of esomeprazole, while not having a significant clinical

values.

Metabolism and excretion Esomeprazole is completely metabolized with the participation of the system of isoenzymes

cytochrome P450 in the liver. Most of

metabolized with

polymorphic isoenzyme CYP2C19,

which is responsible for the formation of hydroxy- and demethylated metabolites.

The remainder of esomeprazole

is metabolized by isoenzyme CYP3A4, responsible for the formation of sulfone esomeprazole, the main metabolite in blood plasma. The half-life (T_1/2) is 1.3 hours with prolonged intake of the drug once a day. The area under the concentration-time curve (AUC) increases upon repeated admission. Dose-dependent increase AUC with repeated application is non-linear due to a decrease in metabolism during the "first passage" through the liver, a decrease in clearance, probably caused by inhibition of the isoenzyme CYP2C19 with esomeprazole and / or him

sulfo-containing metabolite. With a single daily intake

Esomeprazole is completely excreted from the blood plasma during a break between doses. Esomeprazole Do not cumulate.

The main metabolites of esomeprazole do not affect the secretion of hydrochloric acid in the stomach. Almost 80% of the ingested dose of esomeprazole is excreted by the kidneys in the form of metabolites, and the rest - through the intestine. In urine, less than 1% of unchanged esomeprazole is found. Pharmacokinetics in selected patient groups

Approximately 2.9 ± 1.5% of the population, isoenzyme activity is reduced CYP2C19. In such patients, the metabolism of esomeprazole is mainly

isoenzyme CYP3A4. After

a multiple dose of esomeprazole 40 mg once a day, the mean AUC reduced activity CYP2C19. Mean values of the maximum plasma concentrations (C_max) while increasing by about 60%.Have elderly patients (71-80 years) metabolism of esomeprazole does not change significantly.

After a single dose of 40 mg esomeprazole, the mean AUC women are about 30% higher than men. In the future, with a systematic daily intake of esomeprazole once-daily differences in pharmacokinetics in patients both sexes was not observed. These features do not affect the dose and method of administration.

Metabolism of esomeprazole can be disrupted in people with slight or moderate violations of the liver. The rate of metabolism is reduced with severe violations of liver function, which is accompanied by a twofold increase AUC. Therefore, the maximum daily dose of esomeprazole in these patients is 20 mg.

The study of y patients with reduced renal function not carried out. Since the excretion of not esomeprazole itself, but its metabolites through the kidneys, the metabolism of esomeprazole in these patients does not change.

After a second dose of 20 mg and 40 mg

esomeprazole levels AUC and time

achieve maximum concentration

(TC_max) in children aged 12-18 years and adults were the same.

Indications:

- Gastroesophageal reflux disease (GERD):

- treatment of erosive reflux esophagitis;

- long-term maintenance treatment after healing of erosive reflux-esophagitis in order to prevent relapses;

- symptomatic treatment of GERD.

- Stomach ulcer and duodenal ulcer.

- As part of combined antibiotic therapy for eradication Helicobacter pylori:

- duodenal ulcer associated with Helicobacter pylori,

- prevention of recurrences of peptic ulcers associated with Helicobacter pylori.

- Patients taking long-term non-steroidal anti-inflammatory drugs (NSAIDs):

- healing of gastric ulcer associated with the intake of NSAIDs;

- prevention of gastric ulcer and duodenal ulcer associated with the administration of NSAIDs in patients at risk.

- Long-term prophylaxis of recurrent bleeding recurrences from peptic ulcers (after intravenous administration of drugs that reduce the secretion of the gastric glands);

- The Zollinger-Ellison syndrome and other conditions characterized byyshgastric secretion, including idiopathic hypersecretion.

Contraindications:

Hypersensitivity to esomeprazole, substituted benzimidazoles or other components of the drug, children under 12 years of age (no evidence of efficacy and safety) and children over 12 years of age on other indications other than gastroesophageal reflux disease (GERD), concomitant use with atazanavir and nelfinavir (cm section "Interaction with other drugs"), hereditary intolerance to fructose,glucose-galactose malabsorption syndrome or a deficiency of sucrose-isomaltase.

Carefully:

severe renal failure (experience with use is limited).

Pregnancy and lactation:

The use of the drug Emanera is possible only if the expected benefit for the mother exceeds the possible risk to the fetus, because There is insufficient data on the use of esomeprazole in pregnant women.

In epidemiological studies, during the application of the racemic mixture of omeprazole, no fetotoxic effects or fetal developmental disorders were detected.

In studies with esomeprazole, no direct or indirect adverse effects on the development of the embryo or fetus have been detected in animals; Also, there was no direct or indirect adverse effect on the course of pregnancy, childbirth and the postnatal period of the newborn. Pregnant women should prescribe the drug only if the expected benefit to the mother exceeds the possible risk to the fetus.

At present, it is not known whether esomeprazole with breast milk, so do not use Emanera during breastfeeding.

Dosing and Administration:

Inside, not liquid, squeezed a small amount of liquid.

For patients with difficulty swallowing, pour the contents of the capsules into half a glass of still water, stir and drink immediately or within 30 minutes. Then again fill the glass with water halfway, rinse the walls of the glass and drink.

Do not mix the drug with other liquids, t. this can lead to the dissolution of the protective coating of pellets. Pellets should not be chewed or crushed.

Patients who can not swallow independently, the contents of the capsules should be dissolved in still water and enter esomeprazole through a nasogastric tube. It is necessary to check the conformity of the syringe for the administration of the preparation and the probe. Instructions for the preparation and administration of the drug through the nasogastric tube are given in the subsection "Administration of the drug through the nasogastric tube."

Adults and teenagers over 12 years of age

- Gastroesophageal reflux disease (GERD):

- Erosive reflux esophagitis (treatment): 40 mg once a day for 4 weeks. If, after the first course of therapy, esophagitis does not heal or symptoms persist, an additional 4-week course of treatment with esomeprazole is recommended.

- Long-term maintenance treatment after healing of erosive reflux esophagitis to prevent relapse: 20 mg once a day.

- Symptomatic treatment of GERD: 20 mg once a day - patients without esophagitis. If after 4 weeks of therapy the symptoms can not be controlled, a second examination of the patient is necessary. After eliminating the symptoms, you can continue taking Emaner's drug "on demand", i.e. Take 20 mg of the drug once a day if symptoms occur. Patients taking NSAIDs that are at risk for developing gastric or duodenal ulcers are not recommended on-demand treatment.

Adult patients

- Stomach ulcer and duodenal ulcer.

- As part of combined antibiotic therapy for eradication Helicobacter pylori

- Duodenal ulcer associated with Helicobacter pylori and prevention of recurrence of peptic ulcers associated with Helicobacter pylori:

in the composition of combined eradication therapy Helicobacter pylori Included are: Emanera 20 mg, amoxicillin 1 g and clarithromycin 500 mg. All drugs are taken 2 times a day for 7-14 days.

- Patients taking long-term non-steroidal anti-inflammatory drugs (NSAIDs):

- Healing of gastric ulcer associated with the intake of NSAIDs: 20 mg or 40 mg once a day for 4-8 weeks.

- Prevention of gastric ulcer and duodenal ulcer associated with the administration of NSAIDs in patients at risk: the drug Emanera 20 mg or 40 mg 1 per day.

- Long-term prophylaxis of recurrent bleeding recurrences from peptic ulcers (after intravenous administration of drugs that reduce the secretion of the gastric glands): preparation Emanera 40 mg 1 time per

day within 4 weeks after intravenous prophylaxis of repeated bleeding.

- Zollinger-Ellison syndrome and other conditions characterized by increased gastric secretion, including idiopathic hypersecretion: the initial dose of the drug Emanera 40 mg 2 times a day. The dose of the drug and the duration of treatment are selected individually depending on the clinical picture of the disease. The disease in most patients is controlled by taking the drug at a dose of 80 mg to 160 mg per day. If you need to use the drug Emanera more than 80 mg per day, the daily dose is divided into two doses.

Impaired renal function

Patients with impaired renal function do not need to change the dose. The experience with esomeprazole in patients with severe renal insufficiency is limited; In this regard, when prescribing the drug, such patients should be careful. Impaired liver function

Patients with mild or moderate impairment of liver function are not required to change the dose. In severe hepatic insufficiency, the maximum daily dose should not exceed 20 mg.

Elderly patients

Older patients do not need a dose adjustment.

Administration of the drug through a nasogastric tube

When prescribing the drug through a nasogastric tube:

1. Open the capsule and pour the contents of the capsule into a special syringe. Add 25 ml of drinking water and about 5 ml of air into the syringe. For some probes, it may be necessary to dilute the preparation in 50 ml of drinking water in order to prevent the probe from clogging the pellets contained in the capsule.

2. After adding water, immediately shake the syringe until a suspension is obtained.

3. Make sure that the tip is not clogged (pushing slightly on the piston, holding the syringe in position with the tip up).

4. Insert the tip of the syringe into the probe, continuing to hold it pointed upwards.

5. Shake the syringe and flip it down with a tip. Immediately, inject 5-10 ml of the dissolved drug into the probe. After the injection of the solution, return the syringe to its previous position and shake (the syringe should be held up by the tip to avoid clogging the tip).

6. Again, lower the syringe with the tip down and insert another 5-10 ml of solution into the probe. Repeat the procedure until the syringe is empty.

7. If the remainder of the preparation is in the form of a sludge in the syringe: Fill the syringe with 25 ml of water and 5 ml of air and repeat the procedures described in paragraphs 5 and 6. For some probes, 50 ml of drinking water may be needed for this purpose.

Side effects:

Classification of the incidence of adverse events

effects of the World

Health (WHO):

very often> 1/10

often from> 1/100 to <1/10

infrequently from >1/1000 to <1/100

rarely from> 1/10000 to <1/1000

very rarely from <1/10000

frequency is unknown can not be

estimated on the basis of available data.

In each group, undesirable effects

are presented in decreasing order of their

seriousness.

From the nervous system:

often: headache;

infrequently: insomnia, dizziness,

paresthesia, drowsiness;

rarely: depression, agitation,

confusion;

very rarely: hallucinations, aggressive

behavior.

From the respiratory system:

rarely: bronchospasm;

From the digestive system:

often: abdominal pain, constipation, diarrhea,

flatulence, nausea, vomiting;infrequently: dryness mucous membrane

oral cavity, poresyshactivity of "hepatic" enzymes; rarely: stomatitis, candida of the gastro-

intestinal tract, hepatitis (with jaundice or without);

very rarely, hepatic insufficiency, hepatic encephalopathy patients with a history of liver disease;

From the urinary system: very rarely: interstitial nephritis;

On the part of the reproductive system: very rarely: gynecomastia;

From the musculoskeletal system:

rarely: arthralgia, myalgia; very rarely: muscle weakness;

From the skin:

infrequently: dermatitis, skin rash, dermal

itching, urticaria;

rarely: alopecia, photosensitization; very rarely: erythema multiforme,

Stevens-Johnson syndrome, toxic epidermal necrolysis;

From the hematopoiesis: rarely: leukopenia, thrombocytopenia; very rarely: agranulocytosis, pancytopenia; From the sense organs: infrequently: blurred vision; rarely: a change in taste;

Allergic reactions:

rarely: hypersensitivity reactions

(eg, fever, angioedema

swelling, anaphylactic

reaction / anaphylactic shock); Laboratory data: rarely:hyponatremia; very rarely: hypomagnesemia,

hypocalcemia due to severe hypomagnesemia, hypokalemia

due to severe hypomagnesemia. Other:

infrequent: peripheral edema;

rarely: sweating;

very rarely: weakness (malaise).

Overdose:

To date, cases of overdose with the drug Emanera are not described.

Ingestion of esomeprazole at a dose of 280 mg was accompanied by general weakness and symptoms from the gastrointestinal tract. A single intake of 80 mg of esomeprazole was not accompanied by any symptoms. There is no specific antidote.

Esomeprazole actively binds to blood plasma proteins, so hemodialysis is ineffective.

In case of an overdose, symptomatic therapy should be given.

Interaction:

Medications, suction which depends on the pH level Decrease secretion of hydrochloric acid in the stomach on the background of treatment with esomeprazole and other proton

the pump may lead to a change

absorption of drugs, the absorption of which depends on the acidity of the medium. Like antacids and other drugs that reduce gastric acidity

juice, use of esomeprazole can lead to reduced absorption

ketoconazole, itraconazole and

erlotinib, and an increase in the absorption of such drugs as digoxin. Simultaneous reception of omeprazole in a dose

atazanavir (AUC, FROM_max and the minimum concentration in the blood plasma (C_min) decreased by about 75%). An increase in the dose of atazanavir to 400 mg did not compensate for this decrease in exposure. Inhibitors of the proton pump, incl. esomeprazole, should not be taken concomitantly with atazanavir. 20 mg once daily and digoxin increases bioavailability digoxin on 10 % (bioavailability digoxin

increased by up to 30% in two out of ten patients).

It is known about the interaction of omeprazole with some antiretroviral

preparations. The mechanism and the clinical significance of these interactions are not always known. Reducing the acidity of gastric juice with omeprazole therapy may affect absorption antiretroviral

preparations. Also possible

interaction at the level of isoenzyme CYP2C19. On the background of therapy with omeprazole, a decrease in serum concentration some

antiretroviral drugs

(atazanavir and nelfinavir). Therefore, simultaneous use is not recommended. Simultaneous

the use of omeprazole (40 mg once daily) from atazanavir 300 mg/ ritonavir 100 mg) in healthy volunteers is accompanied by a marked decrease bioavailability atazanavir (AUC, FROM_max and the minimum concentration in the blood plasma (C_min) decreased by about 75%). Increase in dose atazanavir up to 400 mg did not compensate effects of omeprazole on bioavailability atazanavir.

the beginning of therapy and when it is canceled.

When 40 mg of omeprazole is used, Cmax and AUC voriconazole (substrate CYP2C19) by 15% and 41%, respectively.

Esomeprazole does not cause a clinically significant change in pharmacokinetics amoxicillin and quinidine.

The time of bleeding with simultaneous administration of warfarin and 40 mg of esomeprazole remains within acceptable limits. but With the simultaneous use of omeprazole with saquinavir the concentration increases saquinavir in the blood serum.

Taking into account similar

pharmacokinetic and

pharmacodynamic properties

omeprazole and esomeprazole,

simultaneous use of esomeprazole with antiretroviral drugs, such as atazanavir and nelfinavir, Not recommended.

Medicinal products drugs,

metabolized CYP2C19 Esomeprazole inhibits CYP2C19, the main isoenzyme of the metabolism of esomeprazole. Thus, with simultaneous use of esomeprazole with drugs in the metabolism of which isoenzyme participates CYP2C19, such as diazepam, citalopram, imipramine, clomipramine, phenytoin etc., the concentration of these drugs in the blood plasma can increase and, accordingly, a reduction in their dose is required.

This is especially important when considering the use of Emaner ® in the necessity ". Thus, with simultaneous use with 30 mg of esomeprazole, the clearance of diazepam decreases (substrate isoenzyme CYP2C19) by 45%. Simultaneous application esomeprazole in a dose of 40 mg leads to enhancing the interaction.

Effect of drugs on the pharmacokinetics of esomeprazole.

Esomeprazole is metabolized by enzymes CYP2C19 and CYP3A4.

With simultaneous use of esomeprazole with clarithromycin (500 mg 2 times a day) (inhibitor CYP3A4), the value increases AUC esomeprazole 2 times.

The simultaneous use of esomeprazole and a combined inhibitor CYP2C19 and CYP3A4 may be accompanied by an increase AUC esomeprazole more than 2 times. Inhibitors CYP2C19 and CYP3A4, for example, voriconazole increased AUC esomeprazole by 280%. Usually, in such situations, dose changes in esomeprazole are not required, but in patients with significant violations of the function of the liver or, if necessary, long-term therapy should decide whether to reduce the dose of esomeprazole.

concentrations phenytoin in blood plasma patients with epilepsy on 13%.

It is recommended that

concentration of phenytoin in plasma at the beginning of therapy esomeprazole and when it is canceled.

When using omeprazole in a dose of 40 mg increases with_max and AUC voriconazole (substrate isoenzyme CYP2C19) by 15% and 41%, respectively.

Time coagulation with simultaneous long-term taking warfarin and esomeprazole in a dose of 40 mg remains within acceptable limits. However, several cases of clinically relevant enhancement index

international normalized

relationship (INR).It is recommended to monitor INR at the beginning and after the concomitant use of esomeprazole and warfarin or other coumarin derivatives.

The use of omeprazole in a dose of 40 mg resulted in an increase in C_max and AUC cilostazol on 18% and 26%,

respectively; for one of the active metabolites cilostazol the increase was 29% and 69%, respectively. The simultaneous use of esomeprazole in a dose of 40 mg from cisapride leads to an increase in

pharmacokinetic parameters cisapride in healthy volunteers: AUC

- by 32% and T1/2 - by 31%, however FROM_max at

This does not change significantly.

Slight lengthening of the interval QT

on the ECG, which is observed when

monotherapy with cisapride, not

increased when adding

esomeprazole.

Some patients reported

increase in concentration

methotrexate in the serum for

A background of simultaneous application with

proton pump inhibitors. When

the use of high doses of methotrexate

should consider

temporary withdrawal of esomeprazole.

Esomeprazole does not cause clinically

significant changes pharmacokinetics

amoxicillin and quinidine.

Simultaneous short

use of esomeprazole and naproxen or

rofecoxib has not revealed clinically

significant pharmacokinetic

interaction.

In the clinical study,

interaction when applying

clopidogrel (300 mg loading dose,

then 75 mg / day) with omeprazole (80 mg)

simultaneously, at the same time in the

for 5 days. The activity of thiol

metabolite (active metabolite)

clopidogrel was reduced by 46% (1 st

day of therapy) and 42% (5th day of therapy),

upon admission clopidogrel and omeprazole in one time. When you receive clopidogrel and omeprazole at one time the mean inhibition of platelet aggregation (IPA) was reduced by 47% (within 24 hours of therapy) and 30% (5th day of therapy). According to the results of another study: omeprazole when used with clopidogrel not simultaneously, at different times, does not have an inhibitory effect on the isoenzyme CYP2C19. In the studies, conflicting evidence of clinical manifestations of interaction with clopidogrel in the main cardiovascular events was recorded. When used simultaneously with tacrolimus it is possible to increase serum concentrations tacrolimus. Effect of drugs on the pharmacokinetics of esomeprazole.

In the metabolism of esomeprazole, isozymes participate CYP2C19 and CYP3A4.

With simultaneous use of esomeprazole with clarithromycin (500 mg 2 times a day) (inhibitor isoenzyme CYP3A4), the value increases AUC esomeprazole 2 times.

The simultaneous use of esomeprazole and a combined inhibitor

isozymes CYP2C19 and CYP3A4, eg, voriconazole can

accompanied by an increase AUC esomeprazole in more than 2 times. Usually by accelerating the metabolism of esomeprazole.

Special instructions:

If you have anxious symptoms (such as a significant, spontaneous loss of body weight, repeated vomiting, dysphagia, vomiting with a trace of blood or melena), and if you suspect or identify a stomach ulcer, you must exclude a malignant tumor, because the use of the drug Emanera can reduce the severity of symptoms and delay the diagnosis.

Patients who have been taking the drug for a long time (especially for more than a year) should be under regular medical supervision.

Patients taking the drug "on demand" should be informed of the need to see a doctor when changing the nature of the symptoms.Taking into account fluctuations in the plasma esomeprazole concentration when the drug is used in the "on demand" mode, interactions with other medicinal products should be considered (see "Interaction with drugs").

When using esomeprazole for the purpose of eradication Helicobacter pylori should take into account the possible interaction between the components of triple therapy. Clarithromycin is a potent inhibitor CYP3A4, therefore, contraindications and drug interactions of clarithromycin should be taken into account in the appointment of triple therapy to patients who simultaneously take drugs metabolized CYP3A4, such as cisapride.

The preparation of Emanera contains sucrose, therefore its use is contraindicated in patients with hereditary intolerance to fructose, glucose-galactose malabsorption syndrome or a deficiency of isomaltase sucrose.

Effect on the ability to drive transp. cf. and fur:

the drug Emanera does not affect the management of vehicles and work with other technical devices that require increased concentration and speed of psychomotor reactions.

Form release / dosage:capsules of 20 and 40 mg.

Packaging:

7 capsules per blister of the combined material OPA / Al / PE + desiccant and aluminum foil + PE (OPA / A1 / PE + dessicant and aluminium foil +PE) or from a combined material OPA / Al / PVC and aluminum foil (OPA/A1/PVC foil and aluminium foil).
For 1, 2, 4 blisters are placed in a pack of cardboard along with instructions for use.

Storage conditions:

At temperatures not higher than 30 ° C, in the original packaging.

Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002047

Date of registration:11.04.2013

Date of cancellation:2018-04-11

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, dd, Novo mesto, AO Slovenia

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp16.10.2013

Illustrated instructions

Instructions

Emanera® (Emanera)