Omeprazole Zentiva (Capsules) Instructions for Use

Marketing Authorization Holder

Zentiva, k.s. (Czech Republic)

Manufactured By

Saneca Pharmaceuticals, a.s. (Slovakia)

ATC Code

A02BC01 (Omeprazole)

Active Substance

Omeprazole (Rec.INN registered by WHO)

Dosage Forms

Omeprazole Zentiva		Enteric-coated capsules 10 mg: 14 or 28 pcs.
		Enteric-coated capsules 20 mg: 14, 28 or 90 pcs.

Dosage Form, Packaging, and Composition

Enteric-coated capsules hard gelatin, size No. 3, with a light brownish-yellow body and a light orange cap; capsule contents – spherical pellets from white to white with a light yellowish-brownish tint.

Excipients: sugar spheres – 83.96 mg (sucrose 80 – 91.5%, corn starch 8.5 – 20%, purified water – 1.5%), anhydrous lactose – 4.09 mg, hypromellose 2910/6 – 8.5 mg, hyprolose – 3.065 mg, sodium lauryl sulfate – 0.255 mg, sodium phosphate dibasic dodecahydrate – 0.41 mg, triethyl citrate – 2.865 mg, talc – 12 mg, methacrylic acid and ethyl acrylate copolymer [1:1] – 24.855 mg.

Capsule shell composition body: iron oxide black (E172) – 0.02%, iron oxide red (E172) – 0.04%, titanium dioxide (E171) – 4%, iron oxide yellow (E172) – 0.22%, gelatin – up to 100%; cap: iron oxide red (E172) – 0.06%, titanium dioxide (E171) – 1.33%, iron oxide yellow (E172) – 0.65%, gelatin – up to 100%.

14 pcs. – dark glass bottles (1) – cardboard packs.
28 pcs. – dark glass bottles (1) – cardboard packs.

Enteric-coated capsules hard gelatin, size No. 2, with a light brownish-yellow body and a light brown cap; capsule contents – spherical pellets from white to white with a light yellowish-brownish tint.

Excipients: sugar spheres – 167.92 mg (sucrose 80 – 91.5%, corn starch 8.5 – 20%, purified water – 1.5%), anhydrous lactose – 8.18 mg, hypromellose 2910/6 – 17 mg, hyprolose – 6.13 mg, sodium lauryl sulfate – 0.51 mg, sodium phosphate dibasic dodecahydrate – 0.82 mg, triethyl citrate – 5.73 mg, talc – 24 mg, methacrylic acid and ethyl acrylate copolymer [1:1] – 49.71 mg.

Capsule shell composition body: iron oxide black (E172) – 0.02%, iron oxide red (E172) – 0.04%, titanium dioxide (E171) – 4%, iron oxide yellow (E172) – 0.22%, gelatin – up to 100%; cap: iron oxide red (E172) – 0.47%, titanium dioxide (E171) – 1%, iron oxide yellow (E172) – 0.45%, gelatin – up to 100%.

14 pcs. – dark glass bottles (1) – cardboard packs.
28 pcs. – dark glass bottles (1) – cardboard packs.
90 pcs. – dark glass bottles (1) – cardboard packs.

Clinical-Pharmacological Group

H⁺-K⁺-ATPase inhibitor. Antiulcer drug

Pharmacotherapeutic Group

Proton pump inhibitor

Pharmacological Action

Antiulcer drug. H⁺-K⁺-ATPase inhibitor.

Omeprazole has a highly selective mechanism of action, resulting in reduced gastric acid secretion. It is a specific inhibitor of the proton pump of gastric parietal cells. The drug’s action is rapid and mediated by reversible inhibition of gastric acid secretion. Omeprazole is a weak base. It concentrates in the acidic environment of the secretory canaliculi of gastric mucosal parietal cells, is activated, and inhibits the proton pump – the enzyme H⁺-K⁺-ATPase.

The effect of omeprazole on the final stage of hydrochloric acid production in the stomach is dose-dependent and provides highly effective inhibition of both basal and stimulated hydrochloric acid secretion, regardless of the stimulating factor.

With daily oral administration, omeprazole provides rapid and effective inhibition of daytime and nighttime hydrochloric acid secretion. The maximum effect is achieved within 4 days of treatment. In patients with duodenal ulcer, omeprazole at a dose of 20 mg causes a sustained reduction in 24-hour gastric acidity by at least 80%. This achieves a reduction in the mean C_max of hydrochloric acid after pentagastrin stimulation by 70% over 24 hours.

In patients with duodenal ulcer, daily administration of omeprazole at a dose of 20 mg maintains an intragastric acidity level of pH >3 for an average of 17 hours.

Inhibition of hydrochloric acid secretion depends on the AUC of omeprazole, not on the plasma concentration of the drug at a given time.

Omeprazole has a bactericidal effect against Helicobacter pylori in vitro. Eradication of Helicobacter pylori when using omeprazole in combination with antibacterial agents is accompanied by rapid symptom relief, a high degree of healing of gastrointestinal mucosal defects, and long-term remission of peptic ulcer disease, which reduces the likelihood of complications such as bleeding as effectively as continuous maintenance therapy.

Pharmacokinetics

Absorption

Omeprazole is rapidly absorbed from the gastrointestinal tract, C_max in plasma is reached in 0.5-1 hour. Omeprazole is absorbed in the small intestine, usually within 3-6 hours. Bioavailability after a single oral dose is approximately 30-40%; after continuous once-daily administration, bioavailability increases to 60%. Food intake does not affect the bioavailability of omeprazole.

Distribution

The plasma protein binding of omeprazole is about 95%, V_d is 0.3 l/kg. Omeprazole does not have a cumulative effect.

Metabolism

Omeprazole is completely metabolized in the liver. The main isoenzymes involved in the metabolism process are CYP2C19 and CYP3A4. Given the high affinity of omeprazole for the CYP2C19 isoenzyme, competitive interaction with other drugs metabolized by this isoenzyme is possible. Hydroxyomeprazole is the main metabolite formed under the action of the CYP2C19 isoenzyme. The resulting metabolites – sulfone and sulfide – do not have a significant effect on hydrochloric acid secretion.

Elimination

T_1/2 is about 40 minutes (30-90 minutes). About 80% is excreted by the kidneys as metabolites, and the rest through the intestines.

Pharmacokinetics in special patient groups

A slight decrease in omeprazole metabolism has been noted in elderly patients.

In chronic renal failure, excretion decreases proportionally to the decrease in creatinine clearance.

In patients with impaired liver function, an increase in AUC is observed.

Indications

For 10 mg capsules

• Symptomatic treatment of reflux symptoms (heartburn, nausea, acid regurgitation) associated with gastroesophageal reflux disease (GERD) in adults.

For 20 mg capsules

• Gastric ulcer;
• Duodenal ulcer;
• NSAID-associated gastric and duodenal ulcers and erosions;
• Eradication of Helicobacter pylori in gastric and duodenal ulcers;
• Reflux esophagitis;
• Symptomatic gastroesophageal reflux disease;
• Dyspepsia associated with increased acidity;
• Zollinger-Ellison syndrome.

ICD codes

Dosage Regimen

The drug is taken orally with a small amount of water (the capsule contents should not be chewed). If there are difficulties swallowing the whole capsule, you can swallow its contents after opening or dissolving the capsule, or you can mix the capsule contents with a slightly acidified liquid (juice, yogurt) and use the resulting suspension within 30 minutes. It should not be taken simultaneously with milk or carbonated water.

For 10 mg capsules

The recommended dose is 1 capsule once a day (preferably in the morning, on an empty stomach).

A reduction in symptom severity is usually noted after 2-3 days of regular use of the drug. In most patients, heartburn completely disappears within 7 days. After complete disappearance of symptoms, treatment should be discontinued.

Treatment without medical supervision is carried out for 14 consecutive days.

For 20 mg capsules

Adults

Duodenal ulcer

Patients with active duodenal ulcer are recommended to take Omeprazole Zentiva 20 mg once a day. The drug provides rapid symptom relief. In most patients, ulcer healing occurs within 2 weeks. In cases where complete ulcer healing does not occur within 2 weeks, healing is achieved with a subsequent 2-week use of Omeprazole Zentiva.

Patients with duodenal ulcer poorly responsive to treatment are usually prescribed Omeprazole Zentiva 40 mg once a day. Ulcer healing usually occurs within 4 weeks.

To prevent relapses, patients with duodenal ulcer are recommended Omeprazole Zentiva 20 mg once a day. If necessary, the dose can be increased to 40 mg once a day.

Gastric ulcer

The recommended dose of Omeprazole Zentiva is 20 mg once a day. The drug provides rapid symptom relief. In most patients, healing occurs within 4 weeks. In cases where complete healing does not occur after the first course of the drug, a repeat 4-week course of treatment is usually prescribed, during which healing is achieved.

Patients with gastric ulcer poorly responsive to treatment are usually prescribed the drug at a dose of 40 mg once a day. Healing is usually achieved within 8 weeks.

To prevent relapses, patients with gastric ulcer are recommended a dose of 20 mg once a day. If necessary, the dose can be increased to 40 mg once a day.

NSAID-associated gastric ulcers or duodenal erosions

In the presence of NSAID-associated gastric ulcers, duodenal ulcers, or gastroduodenal erosions in patients with ongoing NSAID therapy or after its completion, the recommended dose of the drug is 20 mg once a day. The drug provides rapid symptom relief; in most patients, healing occurs within 4 weeks. In those patients who do not heal during the initial therapy period, healing is usually achieved with a repeat 4-week use of the drug.

For duodenal ulcers, erosions, and dyspepsia symptoms associated with NSAID use, the recommended dose of the drug is 20 mg once a day.

Eradication of Helicobacter pylori

The following combinations of triple therapy regimens are most commonly used

• Omeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg twice a day, morning and evening;
• Omeprazole 20 mg + metronidazole 400 mg + clarithromycin 250 mg twice a day, morning and evening;
• Omeprazole 20 mg + metronidazole 400 mg + clarithromycin 500 mg twice a day, morning and evening;
• Omeprazole 40 mg once a day + amoxicillin 500 mg three times a day + metronidazole 400 mg three times a day.

The course of therapy is 7 days.

For a 2-week course of dual therapy, the following combinations are used

• Omeprazole 20-40 mg + amoxicillin 750 mg twice a day;
• Omeprazole 40 mg once a day + clarithromycin 500 mg three times a day or amoxicillin 750-1500 mg twice a day;

In cases where the test for Helicobacter pylori remains positive after the course of treatment, the course of treatment may be repeated.

Reflux esophagitis

The recommended dose is 1 capsule of Omeprazole Zentiva 20 mg once a day. The drug provides rapid symptom relief. In most patients, healing occurs within 4 weeks. In cases where complete healing does not occur after the first course of the drug, a repeat 4-week course of treatment is usually prescribed, during which healing is achieved.

Patients with severe reflux esophagitis are recommended Omeprazole Zentiva at a dose of 40 mg once a day; healing usually occurs within 8 weeks.

Patients with reflux esophagitis in remission are prescribed Omeprazole Zentiva 20 mg once a day as long-term maintenance therapy courses. If necessary, the dose can be increased to 40 mg.

Symptomatic gastroesophageal reflux disease

The recommended dose of Omeprazole Zentiva is 20 mg once a day. The drug provides rapid symptom relief. Individual dose adjustment is not excluded. If symptoms do not disappear after 4 weeks of treatment, further examination of the patient is recommended.

Dyspepsia associated with increased hydrochloric acid production

To relieve pain and/or discomfort in the epigastric region, with or without heartburn, Omeprazole Zentiva 20 mg once a day is prescribed. If symptoms do not disappear after 4 weeks of treatment, further examination of the patient is recommended.

Zollinger-Ellison syndrome

Patients with Zollinger-Ellison syndrome are prescribed the drug in an individual dosage. Treatment is continued according to clinical indications for as long as necessary. The recommended initial dose of the drug is 60 mg daily. In patients with severe disease, as well as in cases where other therapeutic methods have not yielded the desired result, the use of the drug was effective in more than 90% of cases when prescribed at a dose of 20-120 mg daily. In cases where the daily dose of the drug exceeds 80 mg, the dose should be divided into 2 parts and taken twice a day.

In children over 2 years of age and weighing >20 kg the recommended dose of the drug is 20 mg once a day. If necessary, the dose can be increased to 40 mg once a day.

The duration of treatment for reflux esophagitis is 4-8 weeks.

The duration of treatment for symptomatic therapy of heartburn and acid regurgitation in gastroesophageal reflux disease is 2-4 weeks. If symptoms of the disease do not disappear during the use of omeprazole for 2-4 weeks, further examination is recommended.

In children over 4 years of age and adolescents for treatment of duodenal ulcer caused by H. pylori, when choosing an antibiotic for the appropriate combination therapy, the individual patient tolerance of the drugs must be taken into account. Drugs should be prescribed in accordance with resistance patterns and treatment guidelines adopted in the country, at the regional level, and at the local level, taking into account the duration of treatment (most often 7 days, sometimes 14 days) and the appropriate use of antibacterial drugs. Treatment should be carried out under the supervision of a specialist.

The use of the following doses is recommended

Special patient groups

In patients with impaired renal function, dose adjustment is not required.

In patients with impaired liver function, a daily dose of 10-20 mg is usually sufficient.

In elderly patients (over 65 years), dose adjustment is not required.

Adverse Reactions

Side effects of omeprazole are usually minor and reversible. The occurrence of the side effects listed below is possible, which are divided into system-organ classes according to the Medical Dictionary for Regulatory Activities (MedDRA) classification. The WHO classification was used to indicate the frequency of side effects: very common (≥10%), common (≥1% and <10%), uncommon (≥0.1% and <1%), rare (≥0.01% and <0.1%), very rare (<0.01%), frequency not known (it is not possible to determine the frequency of the side effect from the available data).

Hematologic system disorders rarely – leukopenia, thrombocytopenia; very rarely – agranulocytosis, pancytopenia.

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

Metabolism and nutrition disorders rarely – hyponatremia; unknown frequency – hypomagnesemia.

Psychiatric disorders infrequently – insomnia; rarely – agitation, confusion, depression; very rarely – aggression, hallucinations.

Nervous system disorders frequently – headache; infrequently – dizziness, paresthesia, somnolence; rarely – taste disturbance.

Eye disorders rarely – blurred vision.

Ear and labyrinth disorders infrequently – vertigo.

Respiratory, thoracic and mediastinal disorders rarely – bronchospasm.

Gastrointestinal disorders frequently – diarrhea, constipation, nausea, vomiting, flatulence, abdominal pain; infrequently – increased liver enzymes; rarely – dry mouth, stomatitis, gastrointestinal candidiasis, hepatitis (with or without jaundice); very rarely – liver failure, encephalopathy in patients with pre-existing liver disease.

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

Musculoskeletal and connective tissue disorders infrequently – hip, wrist or spine fractures; rarely – arthralgia, myalgia; very rarely – muscle weakness.

Renal and urinary disorders rarely – interstitial nephritis.

Reproductive system and breast disorders very rarely – gynecomastia.

General disorders and administration site conditions infrequently – malaise, peripheral edema; rarely – increased sweating.

Cases of gastric glandular cysts have been reported during long-term treatment with proton pump inhibitors (a consequence of inhibited gastric acid secretion, benign and reversible).

Contraindications

• Concomitant use with atazanavir and nelfinavir;
• Lactase deficiency, sucrase/isomaltase deficiency, lactose intolerance, fructose intolerance, glucose-galactose malabsorption;
• Children under 2 years of age and body weight <20 kg (for treatment of reflux esophagitis, symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease);
• Children under 4 years of age (for treatment of duodenal ulcer caused by H. pylori);
• Children and adolescents under 18 years of age (for 10 mg capsules);
• Hypersensitivity to omeprazole, substituted benzimidazoles or other ingredients of the drug.

With caution the drug should be used in the presence of symptoms such as significant weight loss, frequent vomiting, dysphagia, vomiting blood or melena; in the presence of gastric ulcer (or suspected gastric ulcer), a malignant neoplasm should be excluded, as treatment may mask symptoms and thus delay the correct diagnosis.

Use in Pregnancy and Lactation

Study results have shown no adverse effects of omeprazole on the health of pregnant women, the fetus, or the newborn. Omeprazole Zentiva can be used during pregnancy.

Omeprazole is excreted in breast milk, but exposure to the infant is unlikely when used at therapeutic doses. Omeprazole Zentiva can be used during breastfeeding.

Use in Hepatic Impairment

In patients with impaired liver function, a daily dose of 10-20 mg is usually sufficient.

Use in Renal Impairment

In patients with impaired renal function, dose adjustment is not required.

Pediatric Use

The use of the drug Omeprazole Zentiva 20 mg is contraindicated in children under 2 years of age and with body weight <20 kg (for treatment of reflux esophagitis, symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease); children under 4 years of age (for treatment of duodenal ulcer caused by H. pylori).

The use of the drug Omeprazole Zentiva 10 mg is contraindicated in children and adolescents under 18 years of age.

Geriatric Use

In elderly patients (over 65 years), dose adjustment is not required.

Special Precautions

Before starting therapy, a malignant process must be excluded (especially in gastric ulcer), because treatment, by masking symptoms, may delay the correct diagnosis. If no improvement is observed within 5 days after starting Omeprazole Zentiva or if heartburn worsens, treatment should be discontinued and a doctor should be consulted.

Patients over 45 years of age with symptoms of heartburn occurring for the first time may take Omeprazole Zentiva only after consulting a doctor. Omeprazole Zentiva should not be taken without medical supervision if one of the following symptoms or conditions is present

• Unexplained weight loss and/or loss of appetite, fatigue;
• Prolonged abdominal pain;
• History of gastric and/or duodenal ulcer;
• Frequent vomiting;
• Difficulty swallowing/pain on swallowing;
• Vomiting blood/melena/rectal bleeding;
• Persistent heartburn (more than 3 months);
• Chronic cough, difficulty breathing;
• Jaundice;
• Chest pain (especially chest tightness or pain radiating to the neck or upper limbs) combined with sweating, difficulty breathing or dizziness;
• Family history of gastric or esophageal cancer in close relatives;
• Liver failure;
• Rare hereditary disorders, e.g., galactose intolerance, Lapp lactase deficiency, fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficiency.

If any of these symptoms/conditions occur, treatment should be carried out under medical supervision.

Risk of hip, wrist and spine fractures

Proton pump inhibitors, especially when used in high doses and for long-term use (>1 year), may moderately increase the risk of hip, wrist and spine fractures, particularly in elderly patients or in the presence of other risk factors. Observational study results suggest that proton pump inhibitors may increase the overall risk of fractures by 10-40%. Patients at risk for osteoporosis should receive treatment according to current clinical guidelines.

Hypomagnesemia

Severe hypomagnesemia has been reported in patients receiving Omeprazole for at least 3 months. Fatigue, delirium, seizures, dizziness, and ventricular arrhythmia may occur. In most patients, hypomagnesemia resolved after discontinuation of proton pump inhibitors and administration of magnesium supplements. In patients planned for long-term therapy or 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.

Effect on the absorption of vitamin B₁₂ (cyanocobalamin)

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

Other effects related to inhibition of gastric acid secretion

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

Reduced gastric acid secretion due to proton pump inhibitors or other acid-suppressing agents leads to increased growth of normal gut flora, which in turn may lead to a slightly increased risk of intestinal infections caused by Salmonella spp. and Campylobacter spp. and possibly Clostridium difficile in hospitalized patients.

Due to decreased gastric acid secretion, the concentration of chromogranin A (CgA) increases. Increased CgA levels may affect the results of investigations for neuroendocrine tumors. To prevent this influence, omeprazole should be temporarily discontinued 5 days before testing CgA concentration.

Taking the drug with food does not affect its efficacy.

Effect on ability to drive and use machines

There are no data on the effect of the drug on the ability to drive a car or operate machinery. However, since dizziness, blurred vision and drowsiness may occur during therapy, caution should be exercised when driving vehicles or operating machinery requiring increased concentration and speed of psychomotor reactions.

Overdose

Use of omeprazole in adults at a single dose of 560 mg resulted in symptoms of moderate intoxication. A case of omeprazole use at a single dose of 2400 mg has been described, which did not cause any severe toxic symptoms. With increasing dose, the elimination rate of the drug did not change (first-order kinetics), and no specific treatment was required.

Symptoms dizziness, confusion, apathy, depression, headache, tachycardia, nausea, vomiting, flatulence, diarrhea,

Treatment symptomatic therapy; if necessary – gastric lavage, administration of activated charcoal.

Drug Interactions

The absorption of some drugs may be altered due to decreased gastric acidity.

As with other drugs that suppress gastric acid secretion or antacids, treatment with omeprazole may lead to reduced absorption of posaconazole, erlotinib, ketoconazole or itraconazole, as well as increased absorption of digoxin. Concomitant use of omeprazole 20 mg once daily and digoxin increases the bioavailability of digoxin by 10%.

Concomitant use of omeprazole with clopidogrel resulted in a 46% decrease in the plasma concentration of the active metabolite of clopidogrel on the first day and a 42% decrease on the fifth day of treatment; administering omeprazole and clopidogrel at different times does not exclude the interaction of these drugs. The observed effect is probably due to the inhibitory effect of omeprazole on the CYP2C19 isoenzyme.

Concomitant use of omeprazole with drugs such as atazanavir and nelfinavir is not recommended, as their plasma concentrations decrease when used concomitantly with omeprazole.

Increased plasma concentrations of tacrolimus have been reported with concomitant use with omeprazole. Careful monitoring of tacrolimus plasma concentrations, as well as monitoring of renal function (creatinine clearance), should be performed, and the dose of tacrolimus should be adjusted if necessary.

No interaction with food or antacids has been identified.

Since Omeprazole is metabolized in the liver by the CYP2C19 isoenzyme, the elimination of diazepam, warfarin (R-warfarin), cilostazol, and phenytoin may be slowed. Monitoring of patients taking phenytoin and warfarin is recommended; a dose reduction of the aforementioned drugs may be required. However, concomitant treatment with the drug at a daily dose of 20 mg does not affect the plasma concentration of phenytoin in patients on long-term therapy; concomitant treatment with Omeprazole Zentiva at a daily dose of 20 mg does not lead to a change in coagulation time in patients on long-term warfarin.

Omeprazole does not affect the metabolism of drugs metabolized by the CYP3A4 isoenzyme, such as cyclosporine, lidocaine, quinidine, estradiol, erythromycin, and budesonide. Plasma concentrations of omeprazole and clarithromycin increase with concomitant use of these drugs.

Drugs that inhibit CYP2C19 and CYP3A4 isoenzymes, such as voriconazole, when used concomitantly with omeprazole, may lead to an increase in omeprazole plasma concentrations due to a decrease in the drug’s metabolism rate. Patients with impaired liver function may require a dose reduction during long-term use of Omeprazole Zentiva.

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

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 2 years.

Dispensing Status

10 mg capsules are approved for use as an over-the-counter medicine.

20 mg capsules are prescription-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.