Emezol (Tablets) Instructions for Use

Marketing Authorization Holder

Actavis Group PTC ehf. (Iceland)

Manufactured By

Balkanpharma-Dupnitsa, AD (Bulgaria)

ATC Code

A02BC05 (Esomeprazole)

Active Substance

Esomeprazole (Rec.INN registered by WHO)

Dosage Forms

	Emezol	Gastro-resistant film-coated tablets, 20 mg: 7, 10, 14, 28, 30, 56, 60, 90 or 100 pcs.
		Gastro-resistant film-coated tablets, 40 mg: 7, 10, 14, 28, 30, 56, 60, 90 or 100 pcs.

Dosage Form, Packaging, and Composition

Gastro-resistant film-coated tablets light pink in color, oblong, biconvex.

Excipients : methacrylic acid and ethyl acrylate copolymer [1:1], 30% dispersion – 25.7 mg, talc – 13.73 mg, triethyl citrate – 8.23 mg, hypromellose – 6.85 mg, sugar spheres – 6.14 mg, magnesium stearate – 0.59 mg, hyprolose – 2.17 mg, glyceryl monostearate 40-55 – 1.32 mg, polysorbate 80 – 0.33 mg, microcrystalline cellulose – 182.59 mg, povidone K-29/32 – 15 mg, macrogol 6000 – 9 mg, crospovidone – 6 mg, sodium stearyl fumarate – 0.6 mg; film coating: Opadry Pink 03B34284 (hypromellose – 5.625 mg, titanium dioxide – 2.75 mg, macrogol 400 – 0.563 mg, iron oxide red dye – 0.034 mg, iron oxide yellow dye – 0.028 mg) – 3% (2-4%).

7 pcs. – Al/Al blisters (1) – cardboard packs.
7 pcs. – Al/Al blisters (2) – cardboard packs.
7 pcs. – Al/Al blisters (4) – cardboard packs.
7 pcs. – Al/Al blisters (8) – cardboard packs.
10 pcs. – Al/Al blisters (1) – cardboard packs.
10 pcs. – Al/Al blisters (3) – cardboard packs.
10 pcs. – Al/Al blisters (6) – cardboard packs.
10 pcs. – Al/Al blisters (9) – cardboard packs.
10 pcs. – Al/Al blisters (10) – cardboard packs.

Gastro-resistant film-coated tablets pink in color, oblong, biconvex.

Excipients : methacrylic acid and ethyl acrylate copolymer [1:1], 30% dispersion – 51.4 mg, talc – 27.46 mg, triethyl citrate – 16.46 mg, hypromellose – 13.7 mg, sugar spheres – 12.28 mg, magnesium stearate – 1.18 mg, hyprolose – 4.34 mg, glyceryl monostearate 40-55 – 2.64 mg, polysorbate 80 – 0.66 mg, microcrystalline cellulose – 365.18 mg, povidone K-29/32 – 30 mg, macrogol 6000 – 18 mg, crospovidone – 12 mg, sodium stearyl fumarate – 1.2 mg; film coating: Opadry Pink 03B34285 (hypromellose – 11.25 mg, titanium dioxide – 5.171 mg, macrogol 400 – 1.125 mg, iron oxide red dye – 0.45 mg, iron oxide yellow dye – 0.004 mg) – 3 % (2-4 %).

7 pcs. – Al/Al blisters (1) – cardboard packs.
7 pcs. – Al/Al blisters (2) – cardboard packs.
7 pcs. – Al/Al blisters (4) – cardboard packs.
7 pcs. – Al/Al blisters (8) – cardboard packs.
10 pcs. – Al/Al blisters (1) – cardboard packs.
10 pcs. – Al/Al blisters (3) – cardboard packs.
10 pcs. – Al/Al blisters (6) – cardboard packs.
10 pcs. – Al/Al blisters (9) – cardboard packs.
10 pcs. – Al/Al blisters (10) – cardboard packs.

Clinical-Pharmacological Group

H⁺-K⁺-ATPase inhibitor

Pharmacotherapeutic Group

Gastric secretion reducing agent – proton pump inhibitor

Pharmacological Action

An H⁺-K⁺-ATPase inhibitor, the dextrorotatory isomer of omeprazole. It reduces the secretion of hydrochloric acid in the stomach by specifically inhibiting the proton pump in parietal cells. Being a weak base and converting to the active form in the acidic environment of the secretory tubules of the gastric mucosal parietal cells, it is activated and inhibits the proton pump – the enzyme H⁺-K⁺-ATPase.

It inhibits both basal and stimulated secretion of hydrochloric acid. The effect occurs 1 hour after oral administration of 20 mg or 40 mg. With daily use for 5 days at a dose of 20 mg once a day, the average maximum concentration of hydrochloric acid after stimulation with pentagastrin decreases by 90%.

Pharmacokinetics

After oral administration, Esomeprazole is rapidly absorbed. C_max in plasma is reached in 1-2 hours. The absolute bioavailability of esomeprazole after a single 40 mg dose is 64% and increases to 89% with daily once-daily administration. For the 20 mg dose of esomeprazole, these figures are 50% and 68%, respectively. Plasma protein binding is 97%.

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

The total clearance is approximately 17 L/h after a single dose of esomeprazole and 9 L/h after multiple doses. T_1/2 is 1.3 hours with systematic administration in a once-daily dosing regimen. AUC increases with multiple doses (non-linear dose and AUC relationship with systematic administration, which is a consequence of reduced first-pass metabolism and reduced systemic clearance caused by inhibition of the CYP2C19 enzyme by esomeprazole and/or its sulfonated metabolite). Does not accumulate. Up to 80% of the dose is excreted by the kidneys as metabolites (less than 1% unchanged), the rest is excreted in the bile.

With daily IV administration once a day, Esomeprazole is completely eliminated from the plasma in the interval between administrations, and no tendency for esomeprazole accumulation is noted. With repeated IV administration of esomeprazole at a dose of 40 mg, the average C_max in plasma is approximately 13.6 µmol/L. The overall exposure increases somewhat less (by approximately 30%) with IV administration of esomeprazole compared to oral administration.

When esomeprazole was administered IV at doses of 40 mg, 80 mg, and 120 mg over 30 minutes followed by IV administration at a dose of 4 mg/h or 8 mg/h for 23.5 hours, a linear dependence of AUC on the administered dose was shown.

Indications

Gastroesophageal reflux disease: erosive reflux esophagitis (treatment), prevention of relapses in patients with healed esophagitis, symptomatic treatment of GERD.

As part of combination therapy: eradication of Helicobacter pylori, duodenal ulcer associated with Helicobacter pylori, prevention of recurrence of peptic ulcers in patients with peptic ulcer disease associated with Helicobacter pylori.

Long-term acid-suppressive therapy in patients who have had bleeding from a peptic ulcer (after IV use of drugs that reduce gastric gland secretion, to prevent recurrence).

For healing of gastric ulcers associated with NSAID use.

Prevention of gastric and duodenal ulcers associated with NSAID use in patients at risk.

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

For the prevention of recurrent bleeding from a peptic ulcer after endoscopic hemostasis (for IV administration).

In children (aged 1 to 18 years) as an alternative to oral therapy when it is not possible – for gastroesophageal reflux disease in patients with erosive reflux esophagitis and/or severe symptoms of reflux disease (for IV administration).

ICD codes

Dosage Regimen

Administer orally or intravenously; set the regimen individually based on indication, clinical condition, and patient age.

For erosive reflux esophagitis treatment, take 40 mg once daily for 4 weeks; for unhealed cases, continue for an additional 4 weeks.

For long-term management of healed esophagitis, take 20 mg once daily.

For symptomatic GERD without esophagitis, take 20 mg once daily for 4 weeks; if symptoms persist, perform further investigation.

For Helicobacter pylori eradication, use esomeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg, all taken twice daily for 7 days.

For healing of gastric ulcers associated with NSAIDs, take 20 mg to 40 mg once daily for 4 to 8 weeks.

For prevention of gastric and duodenal ulcers with NSAID use in at-risk patients, take 20 mg once daily.

For Zollinger-Ellison syndrome, start with 40 mg twice daily; adjust dose individually, with most patients requiring 80 mg to 160 mg daily; continue as long as clinically indicated.

For patients with severe liver impairment, a maximum daily dose of 20 mg is recommended.

For oral administration, swallow tablets whole with water; do not chew or crush; take at least 1 hour before food.

For patients with dysphagia, place the tablet in half a glass of still water; stir until the tablets disintegrate; drink the liquid within 30 minutes; always administer the mixture immediately after preparation; do not use other liquids or store for later use.

For intravenous administration in patients where oral therapy is not appropriate, administer as an intravenous infusion over 10 to 30 minutes; do not administer concomitantly with other medications through the same IV line.

In adolescents aged 12 to 18 years for GERD, the oral dose is 20 mg or 40 mg once daily; duration depends on indication and response.

In children aged 1 to 11 years for GERD (IV only when oral not possible), the recommended dose is 10 mg for body weight less than 20 kg or 20 mg for body weight 20 kg or more, once daily.

For the prevention of recurrent peptic ulcer bleeding after endoscopic hemostasis, administer an 80 mg IV bolus over 30 minutes, followed by a continuous infusion of 8 mg per hour for 72 hours.

Adverse Reactions

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

Musculoskeletal and connective tissue disorders rare – arthralgia, myalgia; very rare – muscle weakness.

Nervous system disorders common – headache; uncommon – dizziness, paresthesia, somnolence, disorientation; rare – taste disturbance.

Psychiatric disorders uncommon – insomnia; rare – depression, agitation, confusion; very rare – hallucinations, aggressive behavior.

Gastrointestinal disorders common – abdominal pain, constipation, diarrhea, flatulence, nausea, vomiting; uncommon – dry mouth; rare – stomatitis, gastrointestinal candidiasis; very rare – microscopic colitis (histologically confirmed).

Hepatobiliary disorders uncommon – increased liver enzyme activity; rare – hepatitis; very rare – hepatic failure, encephalopathy in patients with liver disease.

Reproductive system and breast disorders very rare – gynecomastia.

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

Immune system disorders rare – hypersensitivity reactions (including fever, angioedema, anaphylactic reactions/anaphylactic shock).

Respiratory, thoracic and mediastinal disorders rare – bronchospasm.

Renal and urinary disorders very rare – interstitial nephritis.

Eye disorders rare – blurred vision.

Metabolism and nutrition disorders uncommon – peripheral edema; rare – hyponatremia; very rare – hypomagnesemia; hypocalcemia due to severe hypomagnesemia, hypokalemia due to hypomagnesemia.

General disorders and administration site conditions rare – malaise, sweating.

Contraindications

Hypersensitivity to esomeprazole; children under 12 years of age and children over 12 years of age for indications other than gastroesophageal reflux disease (for oral administration); children under 1 year of age and children under 18 years of age for indications other than gastroesophageal reflux disease (for IV administration); breastfeeding period.

Concomitant use of esomeprazole with atazanavir and nelfinavir is contraindicated.

With caution

Severe renal impairment.

Use in Pregnancy and Lactation

Use during pregnancy is possible only if the expected benefit of therapy for the mother outweighs the potential risk to the fetus. Contraindicated for use during breastfeeding.

Use in Hepatic Impairment

Should be used with caution in severe hepatic impairment. Dose adjustment may be required.

Use in Renal Impairment

Should be used with caution in severe renal impairment. Dose adjustment may be required.

Pediatric Use

Contraindicated in children under 12 years of age and children over 12 years of age for indications other than gastroesophageal reflux disease (for oral administration); in children under 1 year of age and children under 18 years of age for indications other than gastroesophageal reflux disease (for IV administration).

Geriatric Use

When using proton pump inhibitors, especially when used in high doses and for a prolonged period (>1 year), the risk of fractures of the hip, wrist, and vertebrae increases, especially in elderly patients.

Special Precautions

In the presence of symptoms such as significant spontaneous weight loss, frequent vomiting, dysphagia, vomiting blood or melena, as well as in the presence (or suspicion) of a gastric ulcer, the possibility of a malignant neoplasm should be excluded, since treatment with esomeprazole may alleviate symptoms and thus delay the correct diagnosis.

During long-term therapy, the patient’s condition should be regularly monitored.

During treatment with proton pump inhibitors, plasma gastrin levels increase 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 resulting from the inhibition of hydrochloric acid secretion.

Esomeprazole, like all acid-reducing drugs, may lead to reduced absorption of vitamin B₁₂ due to hypo- or achlorhydria. This should be considered in patients with risk factors for reduced vitamin B₁₂ absorption during long-term therapy.

When using proton pump inhibitors, especially when used in high doses and for a prolonged period (>1 year), the risk of fractures of the hip, wrist, and vertebrae increases (especially in elderly patients).

Esomeprazole can cause an increase in chromogranin A levels, which may distort the results of examinations for neuroendocrine tumors. Treatment with esomeprazole should be temporarily discontinued at least 5 days before determining chromogranin A.

Effect on ability to drive vehicles and operate machinery

During the use of esomeprazole, patients should exercise caution when driving vehicles and operating machinery, as well as when engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

It is believed that concomitant use may increase plasma concentrations and enhance the effects of imipramine, clomipramine, citalopram.

It is believed that concomitant use may decrease plasma concentrations and clinical efficacy of itraconazole and ketoconazole.

When used concomitantly with clarithromycin, a case of significant increase in the AUC of esomeprazole due to inhibition of its metabolism under the influence of clarithromycin has been described.

Concomitant use may increase plasma concentrations of diazepam and phenytoin, which apparently has no clinical significance.

Reduced secretion of hydrochloric acid in the stomach during treatment with esomeprazole and other proton pump inhibitors may lead to decreased or increased absorption of drugs whose absorption depends on environmental acidity.

When omeprazole and saquinavir were used concomitantly, an increase in the plasma concentration of saquinavir was noted.

When esomeprazole and tacrolimus were used concomitantly, an increase in the plasma concentration of tacrolimus was noted.

In some patients, an increase in methotrexate concentration was noted with concomitant use with proton pump inhibitors. When using high doses of methotrexate, the possibility of temporary discontinuation of esomeprazole should be considered.

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

There is evidence that concomitant use of esomeprazole with clarithromycin, which inhibits the CYP3A4 isoenzyme, leads to a 2-fold increase in the AUC of esomeprazole. Concomitant use of esomeprazole and a combined inhibitor of CYP3A4 and CYP2C19 isoenzymes, such as voriconazole, may lead to more than a 2-fold increase in the AUC for esomeprazole.

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 the plasma concentration of esomeprazole due to accelerated metabolism.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.