Omeprazole capsules 20 mg

Instructions for use for Omeprazole capsules 20 mg

Brand Name: Omeprazole

International Nonproprietary Name: Omeprazole

Dosage Form: capsules

Composition per one capsule:

Active ingredient: Omeprazole pellets – 235 mg, containing omeprazole – 20 mg.

Inactive ingredients in the pellets:

Copolymer of methacrylic acid and ethyl acrylate [1:1] (acrylic coating L30D) – 18.90 %, Calcium carbonate – 2.975 %, Potassium phosphate, dibasic – 1.275 %, Hypromellose – 6.25 %, Mannitol – 17.0 %, Sugar spheres (sucrose) – 8.0 %, Sugar syrup (sucrose) – 30.25 %, Polyethylene glycol 6000 – 2.45 %, Povidone K30 – 0.075 %, Sodium hydroxide – 0.125 %, Sodium lauryl sulfate – 0.45 %, Talc – 2.45 %, Titanium dioxide – 0.80 %, Polysorbate 80 – 0.50 %.

Capsule shell (body): Gelatin up to 100 %, water 14-15 %; (cap): Gelatin up to 100 %, water – 14-15 %, Ponceau 4R – 0.6666 %, Quinoline yellow – 0.1000 %, Patent blue V – 0.0200 %, Titanium dioxide – 1.2999 %.

Description: Hard gelatin capsules size No. 2 with a transparent body and a brown cap, containing white or almost white spherical pellets.

Pharmacotherapeutic group: Gastric secretion inhibitor - proton pump inhibitor.

ATC Code: A02BC01.

Pharmacological properties

Pharmacodynamics

Omeprazole inhibits the H+/K+ ATPase enzyme ("proton pump") in the parietal cells of the stomach and thus blocks the final stage of hydrochloric acid synthesis. This leads to a decrease in basal and stimulated secretion levels, regardless of the stimulating factor. After a single oral dose, the effect of omeprazole begins within the first hour and lasts for 24 hours, with the maximum effect reached after 2 hours. Secretory activity fully recovers within 3–5 days after discontinuation. Due to decreased acid secretion, the concentration of chromogranin A (CgA) increases. Elevated plasma CgA levels may affect the results of examinations for neuroendocrine tumors.

Pharmacokinetics

Distribution

Omeprazole is absorbed in the small intestine, usually within 3-6 hours. Oral bioavailability is approximately 60 %. Food intake does not affect the bioavailability of omeprazole.

Plasma protein binding is about 95 %, the volume of distribution is 0.3 l/kg.

Metabolism

Omeprazole is completely metabolized in the liver. The main enzymes involved in its metabolism are CYP2C19 and CYP3A4. The resulting metabolites - omeprazole sulfone, sulfide, and hydroxy-omeprazole do not have a significant effect on acid secretion.

Total plasma clearance is 0.3-0.6 l/min. The bioavailability of omeprazole increases by approximately 50 % upon repeated administration compared to a single dose.

Elimination

The elimination half-life is about 40 minutes (30-90 minutes). About 80 % is excreted by the kidneys as metabolites, and the rest via the intestines.

Special patient groups

No significant changes in omeprazole bioavailability were noted in elderly patients or patients with impaired renal function. In patients with impaired liver function, an increase in bioavailability and a significant decrease in plasma clearance were observed.

Indications for use

Adults

• Gastric and duodenal ulcer (in the acute phase and for relapse prevention), including cases associated with Helicobacter pylori (as part of combination therapy);
• Erosive and ulcerative lesions of the stomach and duodenum associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs);
• Reflux esophagitis;
• Symptomatic gastroesophageal reflux disease (GERD);
• Dyspepsia associated with hypersecretion;
• Zollinger-Ellison syndrome.

Children and adolescents

Children over 2 years of age with a body weight of at least 20 kg:

• Reflux esophagitis;
• Symptomatic gastroesophageal reflux disease.

Children over 4 years of age and adolescents:

• Duodenal ulcer caused by Helicobacter pylori.

Contraindications

• Sucrase/isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption;
• Hypersensitivity to omeprazole or any other component of the drug;
• Concurrent use with nelfinavir, erlotinib, and posaconazole, or preparations of St. John's wort (Hypericum perforatum);
• Concurrent use with clarithromycin in patients with hepatic impairment;
• Children under 2 years of age;
• Children over 2 years of age for indications other than reflux esophagitis and symptomatic gastroesophageal reflux disease;
• Children over 4 years of age for indications other than reflux esophagitis, symptomatic gastroesophageal reflux disease and Helicobacter pylori-induced duodenal ulcer.

Precautions

• Renal and/or hepatic impairment;
• Patients with osteoporosis;
• Pregnancy;
• Concurrent use with atazanavir (omeprazole dose should not exceed 20 mg per day), clopidogrel, itraconazole, warfarin, cilostazol, diazepam, phenytoin, saquinavir, tacrolimus, clarithromycin, voriconazole, rifampicin;
• Presence of "alarm" symptoms: significant unintentional weight loss, recurrent vomiting, vomiting with blood, dysphagia, melena (black tarry stools);
• Vitamin B12 (cyanocobalamin) deficiency.

Use in pregnancy and lactation

The drug is approved for use during pregnancy and breastfeeding.

Dosage and administration

Orally, with a small amount of water (the capsule contents must not be chewed).

Duodenal ulcer (acute phase) – 20 mg once daily for 2-4 weeks (in resistant cases, up to 40 mg daily).

Gastric ulcer (acute phase) and erosive-ulcerative esophagitis – 20-40 mg once daily for 4-8 weeks.

NSAID-induced erosive-ulcerative gastrointestinal lesions – 20 mg once daily for 4-8 weeks.

Helicobacter pylori eradication – 20 mg twice daily for 7 or 14 days (depending on the regimen) in combination with antibiotics.

Relapse prevention for gastric and duodenal ulcer – 20 mg once daily.

Relapse prevention for reflux esophagitis – 20 mg once daily for a long period (up to 6 months). For on-demand (symptomatic) treatment.

Symptomatic gastroesophageal reflux disease - 20 mg once daily for 4 weeks.

Dyspepsia associated with hypersecretion - 20 mg once daily for 4 weeks.

Zollinger-Ellison syndrome – The dose is selected individually, usually starting from 60 mg daily. If necessary, the dose may be increased to 80-120 mg daily, divided into two doses.

Children and adolescents

Reflux esophagitis and gastroesophageal reflux disease

Children over 2 years weighing more than 20 kg: 20 mg once daily. If necessary, the dose can be increased to 40 mg once daily. The recommended duration of treatment is 4-8 weeks for reflux esophagitis and 2-4 weeks for symptomatic GERD. If symptoms do not resolve after 2-4 weeks, further investigation of the patient is recommended.

Duodenal ulcer caused by Helicobacter pylori - 20 mg once or twice daily for 7-14 days (depending on the regimen) in combination with antibiotics.

Special patient groups

No dose adjustment is required for patients with renal impairment.

No dose adjustment is required for elderly patients.

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

Adverse reactions

Frequency classification: Very common (>1/10), Common (>1/100 to <1/10), Uncommon (>1/1,000 to <1/100), Rare (>1/10,000 to <1/1,000), Very rare (<1/10,000), Frequency not known.

Gastrointestinal disorders: Common – diarrhea, constipation, nausea, vomiting, flatulence, abdominal pain; Uncommon – increased activity of "hepatic" enzymes and alkaline phosphatase (reversible); Rare – dry mouth, taste disturbance, stomatitis, microscopic colitis, gastrointestinal candidiasis; in patients with pre-existing severe liver disease – hepatitis (including with jaundice), impaired liver function, hepatic failure.

Nervous system disorders: In patients with severe comorbidities: Common – headache; Uncommon – dizziness, vertigo, insomnia; Rare – agitation, somnolence, paresthesia, depression, hallucinations; Very rare – aggression; in patients with pre-existing severe liver disease Very rare – encephalopathy.

Musculoskeletal and connective tissue disorders: Uncommon – hip, wrist, or vertebral fractures; Rare – muscle weakness, myalgia, arthralgia.

Blood and lymphatic system disorders: Rare – leukopenia, thrombocytopenia, hypochromic microcytic anemia (in children); Very rare – agranulocytosis, pancytopenia, eosinophilia.

Skin and subcutaneous tissue disorders: Uncommon – pruritus, skin rash, urticaria, dermatitis; Rare – photosensitivity; Very rare – erythema multiforme, alopecia, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Immune system disorders: Rare – angioedema, bronchospasm, interstitial nephritis, anaphylactic reactions, anaphylactic shock, fever.

General disorders and administration site conditions: Uncommon – malaise; Rare – anorexia, blurred vision, peripheral edema, hyponatremia, increased sweating, gynecomastia, benign, reversible gastric glandular cysts during long-term treatment; Frequency not known – hypomagnesemia.

The following are adverse effects, independent of the dosing regimen, observed in clinical trials and post-marketing experience.

Common (>1/100, <1/10)	Headache, abdominal pain, diarrhea, flatulence, nausea/vomiting, constipation
Uncommon (>1/1,000, <1/100)	Dermatitis, pruritus, rash, urticaria, somnolence, insomnia, dizziness, paresthesia, malaise, increased activity of "hepatic" enzymes
Rare (>1/10,000, <1/1,000)	Hypersensitivity reactions (e.g., fever, angioedema, anaphylactic reaction/shock), bronchospasm, hepatitis (with or without jaundice), hepatic failure, encephalopathy in patients with liver disease, arthralgia, myalgia, muscle weakness, leukopenia, thrombocytopenia, agranulocytosis, pancytopenia, depression, hyponatremia, agitation, aggression, confusion, hallucinations, taste disturbance, blurred vision, dry mouth, stomatitis, gastrointestinal candidiasis, alopecia, photosensitivity, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, interstitial nephritis, gynecomastia, sweating, peripheral edema, microscopic colitis.
Frequency not known	Hypomagnesemia, hypocalcemia due to severe hypomagnesemia, hypokalemia due to hypomagnesemia

Cases of gastric glandular cysts have been reported in patients taking gastric secretion inhibitors over a long period; the cysts are benign and resolve spontaneously with continued therapy.

Overdose

Symptoms of overdose include blurred vision, drowsiness, agitation, confusion, headache, increased sweating, dry mouth, nausea, arrhythmia.

There is no specific antidote. Treatment is symptomatic. Hemodialysis is not sufficiently effective.

Drug interactions

Long-term use of omeprazole 20 mg once daily in combination with caffeine, theophylline, piroxicam, diclofenac, naproxen, metoprolol, propranolol, ethanol, cyclosporine, lidocaine, quinidine, and estradiol did not lead to changes in their plasma concentrations.

Concurrent use with omeprazole may increase or decrease the absorption of drugs whose bioavailability is largely determined by gastric acidity (including erlotinib, ketoconazole, itraconazole, posaconazole, iron salts, and cyanocobalamin).

Concurrent use with omeprazole may lead to a significant decrease in the plasma concentration of atazanavir and nelfinavir.

Concurrent use with omeprazole increases the plasma concentration of saquinavir/ritonavir by up to 70 %, without worsening treatment tolerance in HIV-infected patients.

The bioavailability of digoxin increases by 10% when used concomitantly with 20 mg omeprazole. Caution should be exercised when using these drugs together in elderly patients.

Concurrent use with omeprazole may increase plasma concentration and half-life of warfarin (R-warfarin) or other vitamin K antagonists, cilostazol, diazepam, phenytoin, and other drugs metabolized in the liver via the CYP2C19 isoenzyme (dose reduction of these drugs may be required). Concomitant treatment with omeprazole 20 mg daily leads to changes in coagulation time in patients on long-term warfarin; therefore, when omeprazole is used by patients taking warfarin or other vitamin K antagonists, the International Normalized Ratio (INR) should be monitored; in some cases, a reduction in the dose of warfarin or another vitamin K antagonist may be necessary.

Use of omeprazole 40 mg once daily led to an increase in the maximum plasma concentration and AUC of cilostazol by 18% and 26%, respectively; for one of the active metabolites of cilostazol, the increase was 29% and 69%, respectively.

Omeprazole increases the plasma concentration of tacrolimus upon concurrent use, which may require dose adjustment. During combination therapy, plasma tacrolimus concentration and renal function (creatinine clearance) should be carefully monitored.

Inducers of the CYP2C19 and CYP3A4 isoenzymes (e.g., rifampicin, St. John's wort (Hypericum perforatum) may increase the metabolism of omeprazole when used concomitantly, thereby reducing its plasma concentration.

No interaction was noted with concurrently taken antacids. May reduce the absorption of ampicillin esters, iron salts, itraconazole, and ketoconazole (omeprazole increases gastric pH). As a cytochrome P450 inhibitor, it may increase the concentration and reduce the elimination of diazepam, indirect anticoagulants, phenytoin (drugs that are metabolized in the liver via cytochrome CYP2C19), which in some cases may require a reduction in the doses of these drugs. Potentiates the myelosuppressive effect of other drugs.

When methotrexate was used concomitantly with proton pump inhibitors, a slight increase in methotrexate blood concentration was observed in some patients. When treating with high doses of methotrexate, omeprazole should be temporarily discontinued.

Concomitant administration of omeprazole with clarithromycin or erythromycin increases the plasma concentration of omeprazole.

Concomitant administration of omeprazole with amoxicillin or metronidazole does not affect the plasma concentration of omeprazole.

Special instructions

Before starting therapy, it is necessary to exclude the presence of a malignant process (especially in case of gastric ulcer), because treatment, by masking symptoms, may delay the correct diagnosis.

Concomitant administration with food does not affect its efficacy.

If difficulties arise with swallowing the whole capsule, the contents can be swallowed after opening or sucking the capsule, or the capsule contents can be mixed with a slightly acidic liquid (juice, yogurt) and the resulting suspension used within 30 minutes.

At usual dosages, the drug does not affect the speed of psychomotor reactions or concentration.

Studies have noted a pharmacokinetic/pharmacodynamic interaction between clopidogrel (loading dose 300 mg and maintenance dose 75 mg/day) and omeprazole (80 mg/day orally), which leads to an average 46% reduction in exposure to the active metabolite of clopidogrel and an average 16% reduction in maximum inhibition of ADP-induced platelet aggregation. Therefore, the simultaneous use of omeprazole and clopidogrel should be avoided.

Due to decreased secretion of hydrochloric acid, the concentration of chromogranin A (CgA) increases. Elevated plasma CgA levels may affect the results of examinations for neuroendocrine tumors. To prevent this influence, it is necessary to temporarily stop taking omeprazole 5 days before testing the CgA concentration.

The drug should be used with caution if any of the following symptoms or conditions are present: "alarm" symptoms - significant unintentional weight loss, recurrent vomiting, vomiting with blood, dysphagia, change in stool color (black tarry stools).

Proton pump inhibitors, especially when used in high doses and for long-term use (> 1 year), may moderately increase the risk of fractures of the hip, wrist, and vertebrae, particularly in elderly patients or in the presence of other risk factors.

Randomized, double-blind, controlled clinical trials of omeprazole and esomeprazole, including two open-label studies with therapy duration over 12 years, did not confirm an association between osteoporosis-related fractures and the use of proton pump inhibitors.

Although a causal relationship between the use of omeprazole/esomeprazole and osteoporosis-related fractures has not been established, patients at risk for developing osteoporosis or related fractures should be under appropriate clinical supervision. Severe hypomagnesemia has been registered in patients who received omeprazole for at least three months, manifesting with symptoms such as: fatigue, delirium, seizures, dizziness, and ventricular arrhythmia. In most patients, hypomagnesemia resolved after discontinuation of proton pump inhibitors and administration of magnesium supplements.

In patients planned for long-term therapy or who are prescribed omeprazole with digoxin or other drugs that can cause hypomagnesemia (e.g., diuretics), magnesium levels should be assessed before starting therapy and monitored periodically during treatment.

Omeprazole, like all acid-reducing medicines, may lead to reduced absorption of vitamin B12 (cyanocobalamin). This should be considered in patients with reduced body stores of vitamin B12 or risk factors for impaired vitamin B12 absorption during long-term therapy.

In patients taking gastric secretion inhibitors over a long period, the formation of gastric glandular cysts is more frequently noted; these cysts resolve spontaneously with continued therapy. These phenomena are due to physiological changes resulting from the inhibition of hydrochloric acid secretion.

Decreased secretion of hydrochloric acid in the stomach under the influence of proton pump inhibitors or other acid-inhibiting agents leads to increased growth of normal intestinal flora, which in turn may lead to a slight increase in the risk of intestinal infections caused by bacteria of the genus Salmonella spp. and Campylobacter spp., and possibly Clostridium difficile in hospitalized patients.

Effect on ability to drive and operate machinery

Dizziness, drowsiness, and blurred vision may occur when taking the drug; therefore, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Pharmaceutical form

Capsules 20 mg.

10 capsules in a blister pack made of polyvinyl chloride film and printed lacquered aluminum foil.

1, 2, 3, 4, or 5 blister packs along with the package insert are placed in a cardboard carton.

Storage conditions

Store in a dry place, protected from light and moisture, at a temperature not exceeding 25 ^°C. Keep out of reach of children.

Shelf life

3 years. Do not use after the expiration date printed on the packaging.

Regulatory status

Prescription only.

Marketing Authorization Holder / Organization for claims:

JSC "AVVA RUS", Russia, 121614, Moscow, Krylatskie Kholmy St., 30, building 9.

Tel./Fax: +7 (495) 956-75-54.

Manufacturing address:

JSC "AVVA RUS", Russia, 610044, Kirov Region, Kirov, Luganskaya St., 53a.

Tel.: +7 (8332) 25-12-29; +7 (495) 956-75-54.

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