Esomeprazole Canon (Tablets) Instructions for Use

Marketing Authorization Holder

Canonpharma Production, CJS (Russia)

ATC Code

A02BC05 (Esomeprazole)

Active Substance

Esomeprazole (Rec.INN registered by WHO)

Dosage Forms

	Esomeprazole Canon	Gastro-resistant film-coated tablets, 20 mg: 7, 10, 14, 20, 28, 40 or 56 pcs.
		Gastro-resistant film-coated tablets, 40 mg: 7, 10, 14, 20, 28, 40 or 56 pcs.

Dosage Form, Packaging, and Composition

Gastro-resistant film-coated tablets from light green to green with a bluish tint, round, biconvex; the cross-section is from almost white to light yellow.

Excipients: low-substituted hypromellose (hydroxypropylcellulose) – 14 mg, corn starch pregelatinized – 37.2 mg, colloidal silicon dioxide – 2 mg, mannitol – 23 mg, sodium stearyl fumarate – 2 mg, microcrystalline cellulose – 140 mg.

Film coating composition opadry clear – 8 mg (hypromellose (hydroxypropylmethylcellulose) – 6.4 mg, macrogol (polyethylene glycol) – 1.6 mg); Acryl-Ease green – 22 mg (methacrylic acid and ethyl acrylate copolymer (1:1) – 14.52 mg, colloidal silicon dioxide – 0.22 mg, sodium bicarbonate – 0.22 mg, sodium lauryl sulfate – 0.11 mg, yellow iron oxide – 0.154 mg, indigo carmine dye – 0.176 mg, brilliant blue dye – 0.066 mg, talc – 3.63 mg, titanium dioxide – 2.904 mg); triethyl citrate – 2 mg.

7 pcs. – contour cell packaging (1) – cardboard packs.
7 pcs. – contour cell packaging (2) – cardboard packs.
7 pcs. – contour cell packaging (4) – cardboard packs.
10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (4) – cardboard packs.
14 pcs. – contour cell packaging (1) – cardboard packs.
14 pcs. – contour cell packaging (2) – cardboard packs.
14 pcs. – contour cell packaging (4) – cardboard packs.

Gastro-resistant film-coated tablets from light green to green with a bluish tint, round, biconvex; the cross-section is from almost white to light yellow.

Excipients: low-substituted hypromellose (hydroxypropylcellulose) – 28 mg, corn starch pregelatinized – 74.4 mg, colloidal silicon dioxide – 4 mg, mannitol – 46 mg, sodium stearyl fumarate – 4 mg, microcrystalline cellulose – 280 mg.

Film coating composition opadry clear – 16 mg (hypromellose (hydroxypropylmethylcellulose) – 12.8 mg, macrogol (polyethylene glycol) – 3.2 mg); Acryl-Ease green – 44 mg (methacrylic acid and ethyl acrylate copolymer (1:1) – 29.04 mg, colloidal silicon dioxide – 0.44 mg, sodium bicarbonate – 0.44 mg, sodium lauryl sulfate – 0.22 mg, yellow iron oxide – 0.308 mg, indigo carmine dye – 0.352 mg, brilliant blue dye – 0.132 mg, talc – 7.26 mg, titanium dioxide – 5.808 mg); triethyl citrate – 4 mg.

7 pcs. – contour cell packaging (1) – cardboard packs.
7 pcs. – contour cell packaging (2) – cardboard packs.
7 pcs. – contour cell packaging (4) – cardboard packs.
10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (4) – cardboard packs.
14 pcs. – contour cell packaging (1) – cardboard packs.
14 pcs. – contour cell packaging (2) – cardboard packs.
14 pcs. – contour cell packaging (4) – cardboard packs.

Clinical-Pharmacological Group

H⁺-K⁺-ATPase inhibitor

Pharmacotherapeutic Group

Gastric secretion reducing agent – proton pump inhibitor

Pharmacological Action

Pharmacodynamics

Esomeprazole is the S-isomer of omeprazole and reduces gastric acid secretion by specifically inhibiting the proton pump in the parietal cells of the stomach. The S- and R-isomers of omeprazole have similar pharmacodynamic activity.

Mechanism of action

Esomeprazole is a weak base that is converted to the active form in the highly acidic environment of the secretory canaliculi of the gastric parietal cells and inhibits the proton pump – the enzyme H⁺/K⁺-ATPase, thereby inhibiting both basal and stimulated gastric acid secretion.

Effect on gastric acid secretion

After oral administration of 20 mg or 40 mg, the effect of esomeprazole develops within 1 hour. With daily administration of the drug at a dose of 20 mg once a day for 5 days, the mean maximum concentration of gastric acid after pentagastrin stimulation is reduced by 90% (when measuring acid concentration 6-7 hours after taking the drug on the 5th day of therapy).

In patients with GERD and clinical symptoms, after 5 days of daily oral administration of esomeprazole at a dose of 20 mg or 40 mg, the intragastric pH value above 4.0 was maintained for an average of 13 and 17 hours out of 24 hours. Against the background of esomeprazole at a dose of 20 mg/day, intragastric pH above 4.0 was maintained for at least 8, 12, and 16 hours in 76%, 54%, and 24% of patients, respectively.

A correlation has been identified between the plasma concentration of the drug and the inhibition of acid secretion (AUC parameter was used to assess the concentration).

Therapeutic effect achieved as a result of acid secretion inhibition

When taking the drug at a dose of 40 mg, 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 twice a 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 disease do not require subsequent monotherapy with gastric secretion-reducing drugs to treat the ulcer and relieve symptoms after a week of eradication course.

The effectiveness of esomeprazole in endoscopically confirmed bleeding from a peptic ulcer has been shown.

Other effects associated with inhibition of acid secretion

During treatment with gastric secretion-reducing drugs, the concentration of gastrin in plasma increases as a result of reduced acid secretion. Due to the decrease in acid secretion, the concentration of chromogranin A (CgA) increases. An increase in CgA concentration may affect the results of examinations for the detection of neuroendocrine tumors. To prevent this effect, it is necessary to temporarily stop taking esomeprazole 5 days before the CgA concentration test.

In patients who received Esomeprazole for a long time, an increase in the number of enterochromaffin-like cells was noted, probably associated with an increase in plasma gastrin concentration.

In patients taking gastric secretion-reducing drugs for a long period of time, the formation of glandular cysts in the stomach is more often observed. These phenomena are due to physiological changes resulting from pronounced inhibition of acid secretion. The cysts are benign and undergo reverse development.

The use of drugs that suppress gastric acid secretion, including proton pump inhibitors, is accompanied by an increase in the content of microbial flora normally present in the gastrointestinal tract in the stomach. The use of proton pump inhibitors may lead to a slight increase in the risk of gastrointestinal infectious diseases caused by bacteria of the genus Salmonella spp. and Campylobacter spp. and, probably, Clostridium difficile in hospitalized patients.

In two comparative studies with ranitidine, Esomeprazole showed better efficacy in the treatment of gastric ulcers in patients taking NSAIDs, including selective COX-2 inhibitors.

Pharmacokinetics

Absorption and distribution

Esomeprazole is unstable in an acidic environment, so gastro-resistant tablets are used for oral administration. In vivo, only a small part of esomeprazole is converted to the R-isomer.

Food intake slows down and reduces the absorption of esomeprazole in the stomach, but this does not have a significant effect on the effectiveness of acid secretion inhibition.

The drug is rapidly absorbed: maximum plasma concentration is reached 1-2 hours after administration. The absolute bioavailability of esomeprazole after a single 40 mg dose is 64% and increases to 89% with daily once-daily administration. For a 20 mg dose of esomeprazole, these figures are 50% and 68%, respectively. The volume of distribution at steady state in healthy people is approximately 0.22 l/kg body weight. Esomeprazole is 97% bound to plasma proteins.

Metabolism and excretion

Esomeprazole is metabolized by cytochrome P450 isoenzymes. The main part is metabolized with the participation of the specific polymorphic isoenzyme CYP2C19, resulting in the formation of hydroxylated and demethylated metabolites of esomeprazole. The metabolism of the remaining part is carried out by the isoenzyme CYP3A4, resulting in the formation of the sulfo derivative of esomeprazole, which is the main metabolite determined in plasma.

The parameters given below mainly reflect the pharmacokinetic profile in patients with increased activity of the CYP2C19 isoenzyme.

Total clearance is approximately 17 l/h after a single dose and 9 l/h after multiple doses. The half-life is 1.3 hours with systematic once-daily administration. AUC increases with repeated administration of esomeprazole. The dose-dependent increase in AUC with repeated administration of esomeprazole is nonlinear, which is a consequence of reduced first-pass metabolism through the liver, as well as a decrease in systemic clearance, probably caused by inhibition of the CYP2C19 isoenzyme by esomeprazole and/or its sulfo derivative.

With daily once-daily administration, Esomeprazole is completely eliminated from the blood plasma between doses and does not accumulate.

The main metabolites of esomeprazole do not affect gastric acid secretion. When taken orally, up to 80% of the dose is excreted by the kidneys as metabolites, the other part by the intestines. Less than 1% of unchanged esomeprazole is found in the urine.

Pharmacokinetic features in some patient groups

Approximately 2.9±1.5% of the population has reduced activity of the CYP2C19 isoenzyme. In such patients, the metabolism of esomeprazole is mainly carried out using the CYP3A4 isoenzyme. With systematic administration of 40 mg of esomeprazole once a day, the mean AUC value is 100% higher than this parameter in patients with increased activity of the CYP2C19 isoenzyme. The mean maximum plasma concentrations in patients with reduced isoenzyme activity are increased by approximately 60%. These features do not affect the dose and method of use of esomeprazole.

In elderly patients (71-80 years), it undergoes significant changes.

After a single dose of 40 mg of esomeprazole, the mean AUC value in women is 30% higher than in men. With daily once-daily administration of the drug, no differences in pharmacokinetics between men and women are noted. These features do not affect the dose and method of use of esomeprazole.

In patients with mild to moderate hepatic impairment, the metabolism of esomeprazole may be impaired. In patients with severe hepatic impairment, the metabolic rate is reduced, leading to a doubling of the AUC value for esomeprazole.

Pharmacokinetic studies in patients with renal impairment have not been conducted.

Since it is not esomeprazole itself that is excreted by the kidneys, but its metabolite, it can be assumed that the metabolism of esomeprazole in patients with renal impairment does not change.

In children aged 12-18 years, after repeated administration of 20 mg and 40 mg of esomeprazole, the AUC and time to maximum concentration values in blood plasma were similar to the AUC and time to maximum concentration values in adults.

Indications

Gastroesophageal reflux disease (GERD)

Treatment of erosive reflux esophagitis

• Long-term maintenance treatment after healing of erosive reflux esophagitis, prevention of relapses;
• Symptomatic treatment of GERD.

Peptic ulcer of the stomach and duodenum as part of combination therapy

• Treatment of duodenal ulcer associated with Helicobacter pylori;
• Prevention of relapses of peptic ulcer associated with Helicobacter pylori.

Long-term acid-suppressive therapy in patients who have experienced peptic ulcer bleeding (after intravenous use of gastric secretion-reducing drugs to prevent recurrence)

Patients taking NSAIDs long-term

• Treatment of gastric ulcer caused by NSAID use;
• Prevention of gastric and duodenal ulcers caused by NSAID use in patients at risk.

Zollinger-Ellison syndrome or other conditions characterized by pathological hypersecretion of gastric glands, including idiopathic hypersecretion

ICD codes

Dosage Regimen

Orally. The tablet should be swallowed whole, without chewing, with a sufficient amount of water.

Adults and children from 12 years old

Gastroesophageal reflux disease

Treatment of erosive reflux esophagitis 40 mg once a day for 4 weeks.

An additional 4-week course of treatment is recommended in cases where healing of esophagitis does not occur after the first course or symptoms persist.

Long-term maintenance treatment after healing of erosive reflux esophagitis, prevention of relapses 20 mg once a day.

Symptomatic treatment of GERD 20 mg once a day for patients without esophagitis. If symptoms do not disappear after 4 weeks of treatment, an additional examination of the patient should be performed. After symptoms are eliminated, you can switch to an “as needed” regimen – 20 mg once a day when symptoms recur. For patients taking NSAIDs and at risk of developing gastric or duodenal ulcers, treatment on an “as needed” basis is not recommended.

Adults

Peptic ulcer of the stomach and duodenum

As part of combination therapy for Helicobacter pylori eradication

• Treatment of duodenal ulcer associated with Helicobacter pylori: Esomeprazole Canon 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg. All drugs are taken twice a day for 1 week;
• Prevention of relapses of peptic ulcer associated with Helicobacter pylori: Esomeprazole Canon 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg. All drugs are taken twice a day for 1 week.

Long-term acid-suppressive therapy in patients who have experienced peptic ulcer bleeding (after intravenous use of gastric secretion-reducing drugs to prevent recurrence) Esomeprazole Canon 40 mg once a day for 4 weeks after intravenous use of gastric secretion-reducing drugs.

Patients taking NSAIDs long-term

Treatment of gastric ulcer caused by NSAID use Esomeprazole Canon 20 mg once a day; duration of treatment is 4-8 weeks.

Prevention of gastric and duodenal ulcers caused by NSAID use Esomeprazole Canon 20 mg once a day.

Conditions characterized by pathological hypersecretion of gastric glands, including Zollinger-Ellison syndrome and idiopathic hypersecretion the recommended initial dose of Esomeprazole Canon is 40 mg twice a day. Then the dose is selected individually, the duration of treatment is determined by the clinical picture of the disease. There is experience with the use of 80 to 160 mg of esomeprazole per day; when taking the drug at a dose of more than 80 mg/day, it is recommended to divide the required dose into 2 doses.

Renal impairment no dose adjustment of Esomeprazole Canon is required. However, experience with esomeprazole in patients with severe renal impairment is limited, therefore, caution should be exercised when prescribing the drug to this category of patients.

Hepatic impairment for mild to moderate hepatic impairment, no dose adjustment is required. For patients with severe hepatic impairment, the maximum daily dose should not exceed 20 mg.

Elderly patients dose adjustment of the drug is not required.

Adverse Reactions

WHO classification of frequency of adverse effects: very common – ≥1/10 administrations (>10%); common – from ≥1/100 to <1/10 administrations (>1% and <10%); uncommon - from ≥1/1000 to <1/100 administrations (>0.1% and <1%); rare - from ≥1/10000 to <1/1000 administrations (>0.01% and <0.1%); very rare - <1/10000 administrations (<0.01%); frequency unknown - cannot be estimated from the available data. Within each group, adverse effects are presented in order of decreasing severity.

Nervous system disorders : common – headache; uncommon – drowsiness, insomnia, dizziness, paresthesia; rare – agitation, confusion, depression; very rare – aggressive behavior, hallucinations.

Respiratory system disorders rare – bronchospasm.

Gastrointestinal system disorders: common – abdominal pain, diarrhea, flatulence, nausea, vomiting, constipation; uncommon – dry mouth, increased activity of “liver” enzymes; rare – stomatitis, gastrointestinal candidiasis, hepatitis (with or without jaundice); very rare – liver failure, hepatic encephalopathy in patients with pre-existing liver disease, microscopic colitis.

Renal and urinary disorders very rare – interstitial nephritis; frequency unknown – renal failure.

Reproductive system disorders very rare – gynecomastia.

Musculoskeletal system disorders rare – arthralgia, myalgia; very rare – muscle weakness; frequency unknown – fractures of the hip, wrist, vertebrae.

Skin and subcutaneous tissue disorders: uncommon – pruritus, rash, urticaria, dermatitis, peripheral edema; rare – alopecia, photosensitivity, malaise, increased sweating; very rare – Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.

Blood and lymphatic system disorders rare – leukopenia, thrombocytopenia; very rare – agranulocytosis, pancytopenia.

Eye and ear disorders uncommon – blurred vision; rare – taste disturbance.

Immune system disorders: rare – hypersensitivity reactions (e.g., fever, angioedema, anaphylactic reaction/anaphylactic shock).

Investigations rare – hyponatremia; very rare – 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 lack of data on efficacy and safety of the drug in this patient group);
• Children aged 12 to 18 years for all indications except GERD;
• Concomitant use with atazanavir and nelfinavir.

With caution

Severe renal impairment (experience is limited).

Use in Pregnancy and Lactation

Currently, there is insufficient data on the use of esomeprazole during pregnancy. Results of epidemiological studies of omeprazole, which is a racemic mixture, showed no fetotoxic effects or impairment of fetal development. Animal studies revealed no direct or indirect adverse effects on embryo-fetal development, either with esomeprazole or the racemic mixture. The drug should be prescribed to pregnant women only if the expected benefit to the mother outweighs the potential risk to the fetus.

It is not known whether Esomeprazole is excreted in breast milk, therefore the drug should not be used during breastfeeding.

Use in Hepatic Impairment

Patients with mild to moderate hepatic impairment do not require dose adjustment.

For patients with severe hepatic impairment, the maximum daily dose should not exceed 20 mg.

Use in Renal Impairment

Use the drug with caution in patients with severe renal impairment (experience is limited), dose adjustment of Esomeprazole Canon is not required.

Pediatric Use

The use of the drug is contraindicated in children under 12 years of age (due to lack of data on efficacy and safety of the drug in this patient group).

The use of the drug is contraindicated in children aged 12 to 18 years for all indications except GERD.

Geriatric Use

Elderly patients do not require dose adjustment.

Special Precautions

In the presence of any alarm symptoms (e.g., significant spontaneous weight loss, recurrent vomiting, dysphagia, vomiting blood or melena), as well as in the presence of a gastric ulcer (or suspected gastric ulcer), the possibility of malignancy should be excluded, because treatment with esomeprazole may alleviate symptoms and delay diagnosis. Patients taking the drug for a long period (especially more than one year) should be under regular medical supervision. Patients taking Esomeprazole “as needed” should be instructed to contact their physician if the nature of their symptoms changes. Considering the fluctuations in esomeprazole plasma concentration when prescribed “as needed” therapy, the interaction of the drug with other medicinal products should be taken into account (see section “Drug Interactions”).

When using esomeprazole for Helicobacter pylori eradication, the possibility of drug interactions for all components of the triple therapy should be considered. Clarithromycin is a potent inhibitor of the CYP3A4 isoenzyme, therefore, when using eradication therapy in patients receiving other drugs metabolized by the CYP3A4 isoenzyme (e.g., cisapride), possible contraindications and interactions of clarithromycin with these drugs must be considered.

When using proton pump inhibitors, especially in high doses and for prolonged periods (more than 1 year), there may be a risk of hip, wrist, and vertebral fractures (especially in elderly patients). Also noted are the formation of fundic gland polyps in the stomach, decreased absorption of vitamin B12, and the development of hypomagnesemia.

Effect on ability to drive and operate machinery

During treatment, dizziness, blurred vision, and drowsiness may occur, therefore caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Currently, cases of esomeprazole overdose are extremely rare. Oral intake of esomeprazole at a dose of 280 mg was accompanied by general weakness and gastrointestinal symptoms. A single dose of 80 mg of esomeprazole did not cause any adverse effects.

Treatment specific antidote is unknown. Hemodialysis is not very effective. In case of overdose, symptomatic and general supportive therapy is recommended.

Drug Interactions

Effect of esomeprazole on the pharmacokinetics of other drugs

Reduced gastric acid secretion during treatment with esomeprazole and other proton pump inhibitors may lead to altered absorption of drugs whose absorption is pH-dependent. Like antacids and other drugs that reduce gastric acidity, the use of esomeprazole may lead to decreased absorption of ketoconazole, itraconazole and erlotinib, and increased absorption of drugs such as digoxin.

Concomitant administration of esomeprazole 20 mg once daily and digoxin increased the bioavailability of digoxin by 10% (the bioavailability of digoxin increased by up to 30% in two out of 10 patients).

Interactions between esomeprazole and some antiretroviral drugs are known. The mechanisms and clinical significance of these interactions are not always known. Increased pH during esomeprazole therapy may affect the absorption of antiretroviral drugs. Interaction at the level of the CYP2C19 isoenzyme is also possible.

When esomeprazole and some antiretroviral drugs, such as atazanavir and nelfinavir, are co-administered, a decrease in their serum concentrations is observed during esomeprazole therapy. Therefore, their concomitant use is not recommended.

Concomitant use of esomeprazole 40 mg once daily and atazanavir 300 mg/ritonavir 100 mg in healthy volunteers led to a significant decrease in the bioavailability of atazanavir (AUC, as well as C_max and C_min decreased by approximately 75%). Increasing the atazanavir dose to 400 mg did not compensate for the effect of esomeprazole on the bioavailability of atazanavir.

When esomeprazole and saquinavir were used concomitantly, an increase in serum saquinavir concentration was noted; when used with some other antiretroviral drugs, their concentration did not change. Given the similar pharmacokinetic and pharmacodynamic properties of omeprazole and esomeprazole, concomitant use of esomeprazole with antiretroviral drugs such as atazanavir and nelfinavir is not recommended.

Esomeprazole inhibits the CYP2C19 isoenzyme, the main enzyme involved in its metabolism. Accordingly, concomitant use of esomeprazole with other drugs metabolized by the CYP2C19 isoenzyme, such as diazepam, citalopram, imipramine, clomipramine, phenytoin, etc., may lead to increased plasma concentrations of these drugs, which in turn may require a dose reduction. It is especially important to remember this interaction when prescribing Esomeprazole Canon on an “as needed” basis. When 30 mg of esomeprazole and diazepam, a substrate of the CYP2C19 isoenzyme, were taken together, a 45% reduction in the clearance of diazepam was observed.

Administration of esomeprazole 40 mg led to a 13% increase in the residual concentration of phenytoin in epileptic patients. In this regard, it is recommended to monitor plasma phenytoin concentrations at the start of esomeprazole treatment and upon its withdrawal.

Concomitant use of esomeprazole 40 mg leads to a 13% increase in plasma phenytoin concentration in epileptic patients.

It is recommended to monitor plasma phenytoin concentrations at the start of esomeprazole therapy and upon its withdrawal.

When esomeprazole 40 mg once daily is used, the AUC and T_max of voriconazole (a substrate of the CYP2C19 isoenzyme) increase by 15% and 41%, respectively.

Concomitant administration of warfarin and 40 mg esomeprazole does not lead to a change in coagulation time in patients taking warfarin long-term. However, several cases of clinically significant increase in INR have been reported with concomitant use of warfarin and esomeprazole. It is recommended to monitor INR at the beginning and end of concomitant use of esomeprazole and warfarin or other coumarin derivatives.

Concomitant administration of cisapride with 40 mg esomeprazole leads to an increase in the pharmacokinetic parameters of cisapride in healthy volunteers: AUC – by 18% and T_1/2 by 26%, for one of the active metabolites of cilostazol the increase was 29% and 69%, respectively. Concomitant use of esomeprazole 40 mg with cisapride leads to an increase in the pharmacokinetic parameters of cisapride in healthy volunteers: AUC by 32% and T_1/2 by 31%, but C_max did not change significantly.

The slight QT interval prolongation observed with cisapride monotherapy did not increase with the addition of esomeprazole.

Some patients have experienced increased serum methotrexate concentrations during concomitant use with proton pump inhibitors. When high doses of methotrexate are used, temporary discontinuation of esomeprazole should be considered.

Esomeprazole does not cause clinically significant changes in the pharmacokinetics of amoxicillin and quinidine.

Studies evaluating the short-term concomitant use of esomeprazole and naproxen or rofecoxib did not reveal clinically significant pharmacokinetic interaction.

Short-term concomitant use of esomeprazole and naproxen or rofecoxib did not reveal clinically significant pharmacokinetic interaction.

A clinical study investigated the interaction when clopidogrel (300 mg loading dose, then 75 mg/day) was used with esomeprazole (80 mg) simultaneously, at the same time for 5 days. The activity of the thiol metabolite (active metabolite) of clopidogrel was reduced by 46% (day 1 of therapy) and 42% (day 5 of therapy) when clopidogrel and omeprazole were taken at the same time. When clopidogrel and esomeprazole were taken at the same time, the mean inhibition of platelet aggregation (IPA) was reduced by 47% (over 24 hours of therapy) and 30% (day 5 of therapy).

According to another study: Esomeprazole when used with clopidogrel not simultaneously, at different times, does not have an inhibitory effect on the CYP2C19 isoenzyme. Studies have reported conflicting data on the clinical manifestations of cardiovascular interaction with clopidogrel.

Concomitant use with tacrolimus may increase serum tacrolimus concentrations.

Effect of drugs on the pharmacokinetics of esomeprazole

Isoenzymes CYP2C19 and CYP3A4 are involved in the metabolism of esomeprazole.

Concomitant use of esomeprazole with clarithromycin (500 mg twice daily), which inhibits the isoenzyme, doubles the AUC values of esomeprazole.

Concomitant use of esomeprazole and a combined inhibitor of the CYP3A4 and CYP2C19 isoenzymes, for example, voriconazole, may lead to a more than 2-fold increase in the AUC value for esomeprazole. As a rule, in such cases, no dose adjustment of esomeprazole is required.

Drugs that induce CYP2C19 and CYP3A4 isoenzymes, such as rifampicin and St. John’s wort preparations, when used concomitantly with esomeprazole, may lead to a decrease in esomeprazole plasma concentration due to accelerated metabolism of esomeprazole.

Storage Conditions

The drug should be stored in a dry place, protected from light and out of the reach of children at 25°C (77°F).

Shelf Life

Shelf life – 2 years.

Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.