OmeVel^® (Capsules) Instructions for Use

Marketing Authorization Holder

Velpharm, LLC (Russia)

Manufactured By

Velpharm, LLC (Russia)

Or

Velpharm-M, LLC (Russia)

ATC Code

A02BC01 (Omeprazole)

Active Substance

Omeprazole (Rec.INN WHO registered)

Dosage Form

OmeVel®

Enteric-coated capsules 20 mg: 7, 10, 14, 20, 21, 28, 30, 35, 40, 42, 50, 56, 60, 70, or 84 pcs.

Dosage Form, Packaging, and Composition

Enteric-coated capsules hard gelatin size 2, with a white body and a yellow cap; capsule contents – white or almost white pellets.

Excipients of pellets acrylic coating L30D, calcium carbonate, potassium dihydrogen phosphate, hypromellose (hydroxypropyl methylcellulose), mannitol, sugar pellets (sucrose), sugar syrup (sucrose), macrogol-6000, povidone K-30, sodium hydroxide, sodium lauryl sulfate, talc, titanium dioxide, polysorbate-80.

Composition of gelatin capsule gelatin; body titanium dioxide; cap dye sunset yellow, dye quinoline yellow, titanium dioxide.

7 pcs. – blister packs (1) – cardboard packs.
7 pcs. – blister packs (2) – cardboard packs.
7 pcs. – blister packs (3) – cardboard packs.
7 pcs. – blister packs (4) – cardboard packs.
7 pcs. – blister packs (5) – cardboard packs.
7 pcs. – blister packs (6) – cardboard packs.
10 pcs. – blister packs (1) – cardboard packs.
10 pcs. – blister packs (2) – cardboard packs.
10 pcs. – blister packs (3) – cardboard packs.
10 pcs. – blister packs (4) – cardboard packs.
10 pcs. – blister packs (5) – cardboard packs.
10 pcs. – blister packs (6) – cardboard packs.
14 pcs. – blister packs (1) – cardboard packs.
14 pcs. – blister packs (2) – cardboard packs.
14 pcs. – blister packs (3) – cardboard packs.
14 pcs. – blister packs (4) – cardboard packs.
14 pcs. – blister packs (5) – cardboard packs.
14 pcs. – blister packs (6) – cardboard packs.
10 pcs. – polymer jars (1) – cardboard packs.
20 pcs. – polymer jars (1) – cardboard packs.
30 pcs. – polymer jars (1) – cardboard packs.
40 pcs. – polymer jars (1) – cardboard packs.
50 pcs. – polymer jars (1) – cardboard packs.
60 pcs. – polymer jars (1) – cardboard packs.

Clinical-Pharmacological Group

H⁺-K⁺-ATPase inhibitor. Antiulcer drug

Pharmacotherapeutic Group

Acid-related disorder treatment agents; antiulcer agents and agents for the treatment of gastroesophageal reflux disease (GERD); proton pump inhibitors

Pharmacological Action

An H⁺-K⁺-ATPase inhibitor, it is a weak base. It inhibits the activity of H⁺-K⁺-ATPase in the parietal cells of the stomach and thereby blocks the final stage of hydrochloric acid secretion. This leads to a decrease in the level of basal and stimulated secretion, regardless of the nature of the stimulus. Due to the decrease in acid secretion, it reduces or normalizes the effect of acid on the esophagus in patients with reflux esophagitis.

Omeprazole has a bactericidal effect on Helicobacter pylori. Eradication of H. pylori with the simultaneous use of omeprazole and antibiotics allows for rapid relief of disease symptoms, achievement of a high degree of healing of the damaged mucosa and sustained long-term remission, and reduces the likelihood of gastrointestinal bleeding.

Pharmacokinetics

When taken orally, it is rapidly absorbed from the gastrointestinal tract. Penetrates into the parietal cells of the gastric mucosa. Plasma protein binding is about 95%, mainly with albumin. Biotransformed in the liver. Excreted by the kidneys – 72-80%, with feces – about 20%. T_1/2 0.5-1 h. T_1/2 after IV administration is 40 min and does not change with long-term treatment.

In patients with chronic liver diseases, T_1/2 increases to 3 h. In patients with impaired liver function, an increase in the bioavailability of omeprazole and a significant decrease in plasma clearance are noted.

Indications

For oral administration

Gastric and duodenal ulcer in the acute phase (including associated with Helicobacter pylori), reflux esophagitis, Zollinger-Ellison syndrome, erosive and ulcerative lesions of the stomach and duodenum associated with NSAID use.

Gastroesophageal reflux disease in children over 2 years of age, duodenal ulcer associated with Helicobacter pylori (as part of combination therapy) in children over 4 years of age.

For IV administration

Omeprazole for IV administration is indicated as an alternative to oral administration.

Gastric and duodenal ulcer; erosive and ulcerative lesions of the stomach associated with NSAID use; erosive and ulcerative lesions of the duodenum associated with NSAID use; stress ulcers; symptomatic gastroesophageal reflux disease; reflux esophagitis; Zollinger-Ellison syndrome; prevention of aspiration of gastric contents into the airways during general anesthesia (Mendelson’s syndrome).

ICD codes

Dosage Regimen

Individual.

When taken orally, a single dose is 20-40 mg. The daily dose is 20-80 mg; frequency of application is 1-2 times/day. Duration of treatment is 2-8 weeks.

Omeprazole can be administered intragastrically through a nasogastric tube in the appropriate dosage form according to the method described in the instructions for the drug used.

IV drip at a dose of 40-120 mg/day. The frequency of administration depends on the indications and the treatment regimen used.

Adverse Reactions

From the digestive system often — diarrhea, constipation, abdominal pain, nausea, vomiting, flatulence; rarely – dry mouth, stomatitis, gastrointestinal candidiasis, microscopic colitis. Cases of glandular cyst formation in the stomach have been reported in patients taking gastric secretion-reducing drugs for a long period of time; they resolve spontaneously with continued therapy.

From the liver and biliary tract: infrequently – increased activity of ‘liver’ enzymes; rarely – hepatitis (with or without jaundice), liver failure, encephalopathy in patients with liver diseases.

From the hematopoietic system rarely – leukopenia, thrombocytopenia, agranulocytosis, pancytopenia, hypochromic microcytic anemia in children.

From the nervous system often – headache; infrequently – vertigo, paresthesia, drowsiness; rarely – taste disturbance.

From the musculoskeletal system: infrequently – fractures of the hip, wrist and vertebrae; rarely – arthralgia, myalgia, muscle weakness.

From the skin and subcutaneous tissues infrequently – dermatitis, rash, itching, urticaria; rarely – alopecia, photosensitivity, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

From the immune system rarely – hypersensitivity reactions (e.g., angioedema, fever, anaphylactic reaction/anaphylactic shock).

From metabolism rarely – hyponatremia; very rarely – hypocalcemia due to severe hypomagnesemia, hypokalemia due to hypomagnesemia; unspecified frequency – hypomagnesemia.

From the psyche infrequently – insomnia; rarely – agitation, aggression, confusion, hallucinations, depression.

From the organ of vision rarely – blurred vision.

From the respiratory system rarely – bronchospasm.

From the kidneys and urinary tract rarely – interstitial nephritis.

From the genital organs and mammary gland: rarely – gynecomastia.

General reactions infrequently – malaise; rarely – sweating, peripheral edema.

Contraindications

For oral administration

Hypersensitivity to omeprazole, substituted benzimidazoles; concomitant use with erlotinib, posaconazole, clarithromycin in patients with hepatic insufficiency, St. John’s wort preparations; breastfeeding period.

Children under 18 years of age, except for: gastroesophageal reflux disease in children over 2 years of age and weighing more than 20 kg; duodenal ulcer associated with Helicobacter pylori – in children over 4 years of age and weighing more than 31 kg.

With caution: osteoporosis, significant spontaneous weight loss, frequent vomiting, dysphagia, vomiting blood or melena, as well as in the presence of a gastric ulcer (or suspicion of a gastric ulcer), pregnancy.

For IV administration

Hypersensitivity to omeprazole, other substituted benzimidazoles; children and adolescents under 18 years of age; simultaneous use with erlotinib, posaconazole, nelfinavir, atazanavir and St. John’s wort preparations; simultaneous use with clarithromycin in patients with hepatic insufficiency.

With caution osteoporosis, hepatic insufficiency, vitamin B₁₂ deficiency, pregnancy, breastfeeding period. Simultaneous use with clopidogrel, itraconazole, warfarin, cilostazol, diazepam, phenytoin, saquinavir, tacrolimus, clarithromycin, voriconazole, rifampicin. Presence of the following ‘alarm’ symptoms; significant weight loss, recurrent vomiting, vomiting blood (hematemesis), swallowing disorder, change in stool color (tarry stool – melena

Use in Pregnancy and Lactation

Use during pregnancy and breastfeeding is possible depending on the dosage form used.

Use in Hepatic Impairment

In patients with impaired liver function, an increase in the bioavailability of omeprazole and a significant decrease in plasma clearance are noted.

Concomitant use with clarithromycin is contraindicated in patients with hepatic insufficiency.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age, except for: gastroesophageal reflux disease in children over 2 years of age and weighing more than 20 kg; duodenal ulcer associated with Helicobacter pylori – in children over 4 years of age and weighing more than 31 kg.

Geriatric Use

The rate of metabolism of omeprazole in elderly patients is somewhat reduced, but dose adjustment is not required.

Special Precautions

Before starting therapy, it is necessary to exclude the possibility of a malignant process (especially with gastric ulcer), because treatment with omeprazole may mask symptoms and delay correct diagnosis.

During the use of omeprazole, distortion of the results of laboratory tests of liver function and plasma gastrin concentration indicators is possible.

Although a causal relationship between the use of omeprazole/esomeprazole and fractures against the background of osteoporosis has not been established, patients at risk of developing osteoporosis or fracture against its background should be under appropriate clinical supervision.

The possibility of measuring magnesium content before starting proton pump inhibitor therapy and periodic monitoring during treatment should be considered

Effect on ability to drive vehicles and operate machinery

Since dizziness, blurred vision and drowsiness may be observed during therapy, patients should be cautious when driving vehicles or when working with machinery requiring increased concentration and speed of psychomotor reactions.

Drug Interactions

When used concomitantly, cases of symptoms of toxic effects of benzodiazepines have been described, which is associated with inhibition of the activity of CYP3A isoenzymes and, apparently, CYP2C9.

When used concomitantly with atracurium besilate, the effects of atracurium besilate are prolonged.

When used concomitantly with bismuth tripotassium dicitrate, an undesirable increase in bismuth absorption is possible.

When used concomitantly with digoxin, a slight increase in the plasma concentration of omeprazole is possible. At an omeprazole dose of 20 mg/day, the bioavailability of digoxin increases by 10%.

When used concomitantly with disulfiram, a case of impaired consciousness and catatonia has been described; with indinavir – a decrease in the plasma concentration of indinavir is possible; with ketoconazole – a decrease in the absorption of ketoconazole.

With long-term concomitant use with clarithromycin, an increase in the plasma concentrations of omeprazole and clarithromycin occurs.

Decreased absorption of erlotinib was observed.

When used concomitantly with theophylline, a slight increase in the clearance of theophylline is possible.

Cases of increased plasma concentration of cyclosporine have been described with concomitant use with cyclosporine.

When used concomitantly with erythromycin, a case of increased plasma concentration of omeprazole has been described, while the effectiveness of omeprazole decreased.

Omeprazole has been shown to interact with some antiretroviral drugs. The mechanisms and clinical significance of these interactions are not always known. An increase in pH during omeprazole therapy may affect the absorption of antiretroviral drugs. Interaction at the level of the CYP2C19 isoenzyme is also possible. When omeprazole and some antiretroviral drugs, such as atazanavir and nelfinavir, are used concomitantly, a decrease in their serum concentration is observed during omeprazole therapy. Therefore, concomitant use of omeprazole with antiretroviral drugs such as atazanavir and nelfinavir is not recommended.

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

Concomitant use of omeprazole with other drugs metabolized by the CYP2C19 isoenzyme, such as diazepam, warfarin (R-warfarin) or other vitamin K antagonists, phenytoin and cilostazol, may lead to a slowdown in the metabolism of these drugs. Monitoring of patients taking phenytoin and Omeprazole is recommended; a reduction in the phenytoin dose may be required. However, concomitant treatment with omeprazole at a daily dose of 20 mg does not affect the plasma concentration of phenytoin in patients on long-term medication. In patients using omeprazole and receiving warfarin or other vitamin K antagonists, INR monitoring is necessary; in some cases, a reduction in the dose of warfarin or another vitamin K antagonist may be required. At the same time, concomitant treatment with omeprazole at a daily dose of 20 mg does not lead to a change in coagulation time in patients on long-term warfarin. The use of omeprazole at a dose of 40 mg once/day led to an increase in C_max and AUC of cilostazol by 18% and 26%, respectively; for one of the active metabolites of cilostazol, the increase was 29% and 69%, respectively.

Studies have shown 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 a decrease in exposure to the active metabolite of clopidogrel by an average of 46% and a decrease in maximum inhibition of ADP-induced platelet aggregation by an average of 16%. The clinical significance of this interaction is unclear. An increased risk of cardiovascular complications with the combined use of clopidogrel and proton pump inhibitors, including omeprazole, has not been shown in randomized clinical trials. The results of a number of observational studies are contradictory and do not provide a clear answer about the presence or absence of an increased risk of thromboembolic cardiovascular complications with the combined use of clopidogrel and proton pump inhibitors.

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

In some patients, a slight increase in the plasma concentration of methotrexate was reported with its concomitant use with proton pump inhibitors. When using high doses of methotrexate, omeprazole should be temporarily discontinued.

Omeprazole is metabolized by the CYP2C19 and CYP3A4 isoenzymes. Concomitant use of omeprazole and inhibitors of the CYP2C19 and CYP3A4 isoenzymes, such as clarithromycin, erythromycin and voriconazole, may lead to an increase in the plasma concentration of omeprazole due to a slowdown in its metabolism. Concomitant use of omeprazole and voriconazole leads to a more than twofold increase in the AUC of omeprazole. Due to the good tolerability of high doses of omeprazole, no dose adjustment of omeprazole is required with short-term concomitant use of these drugs.

Drugs that induce the CYP2C19 and CYP3A4 isoenzymes, such as rifampicin and St. John’s wort preparations, when used concomitantly with omeprazole, may lead to a decrease in its plasma concentration 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.