Omeprazole krka

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT OMEPRAZOLE KRKA (Omeprazol KRKA)

Composition:

Active substance: omeprazole;

One capsule contains 20 mg of omeprazole;

Excipients: hydroxypropylcellulose, magnesium carbonate heavy, sucrose, corn starch, sodium lauryl sulfate, methacrylic acid copolymer dispersion, talc, macrogol 6000, titanium dioxide (E 171);

Capsule shell composition: iron oxide red (E 172), gelatin, titanium dioxide (E 171).

Pharmaceutical form. Capsules.

Main physicochemical properties: two-colored capsules – the body of the capsule is light pink, the cap is brownish-pink; the capsules contain granules from white to light yellow or light pink in color.

Pharmacotherapeutic group. Drugs for treatment of peptic ulcer and gastroesophageal reflux disease. Proton pump inhibitors.

ATC code A02BC01.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

Omeprazole, a racemic mixture of two enantiomers, reduces gastric acid secretion through a targeted mechanism of action. It is a specific inhibitor of the gastric proton pump in parietal cells. It acts rapidly and provides reversible suppression of gastric acid secretion with once-daily dosing.

Omeprazole is a weak base that accumulates and is converted into its active form in the acidic environment of intracellular canaliculi of parietal cells, where it inhibits the enzyme H⁺K⁺-ATPase – the acid pump. This effect on the final stage of gastric acid production is dose-dependent and results in highly effective inhibition of both basal and stimulated acid secretion, regardless of the nature of the stimulus.

Pharmacodynamic effects

All observed pharmacodynamic effects can be explained by the effect of omeprazole on acid secretion.

Effect on gastric acid secretion

Oral administration of 20 mg omeprazole once daily leads to rapid and effective inhibition of daytime and nighttime gastric acid secretion, with maximum effect achieved within 4 days of treatment. In patients with duodenal ulcer, mean reduction in gastric acidity is approximately 80% over 24 hours after administration of 20 mg omeprazole; mean reduction in peak acid output following pentagastrin stimulation is about 70% at 24 hours after omeprazole administration.

Oral administration of 20 mg omeprazole maintains intragastric pH ≥ 3 for a mean duration of 17 hours out of a 24-hour period in patients with duodenal ulcer.

Due to reduced acid secretion and intragastric acidity, omeprazole reduces/normalizes acid exposure of the esophagus in patients with gastroesophageal reflux disease, depending on dose. Inhibition of acid secretion correlates with the area under the plasma concentration–time curve (AUC) of omeprazole, rather than with actual plasma concentration at any given time.

No tachyphylaxis has been observed during omeprazole treatment.

Effect on H. pylori

Peptic ulcer disease is associated with H. pylori, including duodenal ulcer and gastric ulcer. H. pylori is considered the main causative factor in the development of gastritis. H. pylori together with gastric acid is a major factor in the development of peptic ulcer disease. H. pylori is the primary factor in the development of atrophic gastritis, which is associated with an increased risk of gastric cancer.

The reduction of pH achieved with omeprazole in combination with antimicrobial agents is associated with rapid symptom relief, high healing rates of mucosal lesions, and prolonged remission of peptic ulcer disease.

Other effects related to acid suppression

During long-term treatment, a slightly increased frequency of gastric fundic gland polyps has been reported. These changes are a physiological consequence of sustained acid suppression, the polyps are benign, and appear to be reversible.

Reduction of gastric acidity by any means, including proton pump inhibitors, increases the number of bacteria normally present in the gastrointestinal tract. Treatment with acid-reducing agents slightly increases the risk of gastrointestinal infections caused by, for example, Salmonella and Campylobacter, and in hospitalized patients, by Clostridium difficile.

During treatment with antisecretory drugs, serum gastrin increases in response to reduced acid secretion. Serum chromogranin A (CgA) levels also rise due to decreased gastric acidity. Elevated CgA levels may interfere with investigations for neuroendocrine tumors.

Available published data indicate that proton pump inhibitor (PPI) therapy should be discontinued for a period of 5 days to 2 weeks before measuring CgA. This allows CgA levels, which may be elevated after PPI treatment, to return to the baseline range.

Use in pediatrics

In an uncontrolled study in children (aged 1 to 16 years) with severe erosive esophagitis, omeprazole at doses of 0.7–1.4 mg/kg improved esophagitis in 90% of cases and significantly reduced reflux symptoms. In a blinded study without a comparator, infants aged 0 to 24 months diagnosed with gastroesophageal reflux disease were treated with omeprazole doses of 0.5 mg/kg, 1.0 mg/kg, and 1.5 mg/kg. The frequency of vomiting/regurgitation episodes decreased by 50% after 8 weeks of treatment, regardless of dose.

Eradication of H. pylori in children

In a randomized, double-blind clinical trial (Héliot study), omeprazole in combination with two antibiotics (amoxicillin and clarithromycin) was found to be safe and effective in treating H. pylori infection in children aged 4 years and older with gastritis: H. pylori eradication rate was 74.2% (23/31 patients) in the omeprazole + amoxicillin + clarithromycin group, compared to 9.4% (3/32 patients) in the amoxicillin + clarithromycin group. However, no clinical benefit regarding dyspeptic symptoms was demonstrated. This study does not provide information on children under 4 years of age.

Pharmacokinetics.

Absorption

Omeprazole and omeprazole magnesium are acid-labile and therefore administered orally in the form of enteric-coated granules in capsules or tablets. Omeprazole absorption is rapid, with peak plasma levels reached approximately 1–2 hours after dose administration. Absorption of omeprazole occurs in the small intestine and is usually complete within 3–6 hours. Concomitant food intake has no effect on bioavailability. Systemic availability (bioavailability) of omeprazole from a single oral dose of omeprazole is approximately 40%. After repeated once-daily administration, bioavailability increases to approximately 60%.

Distribution

The apparent volume of distribution in healthy subjects is approximately 0.3 L/kg body weight. Omeprazole plasma protein binding is 97%.

Metabolism

Omeprazole is completely metabolized by the cytochrome P450 system.

The majority of omeprazole metabolism depends on CYP2C19, which is responsible for the formation of hydroxyomeprazole, the main metabolite in plasma. The remaining portion depends on another specific isoenzyme, CYP3A4, responsible for the formation of omeprazole sulfone. Due to the high affinity of omeprazole for CYP2C19, there is potential for competitive inhibition and metabolic interactions with other drugs that are substrates for CYP2C19. However, due to low affinity for CYP3A4, omeprazole has no potential to inhibit the metabolism of other CYP3A4 substrates. In addition, omeprazole has no inhibitory effect on major CYP enzymes.

Approximately 3% of the Caucasian population and 15–20% of Asian populations lack functional CYP2C19 enzyme. In these individuals, omeprazole metabolism is likely primarily catalyzed by CYP3A4. After repeated once-daily administration of 20 mg omeprazole, mean AUC was 5–10 times higher in poor metabolizers compared to individuals with functional CYP2C19 (extensive metabolizers). Mean peak plasma concentrations were also 3–5 times higher. These observations have no implications for omeprazole dosing.

Elimination

The terminal half-life of omeprazole in plasma is typically less than 1 hour, both after single and multiple once-daily oral doses. Omeprazole is completely eliminated from plasma between doses, with no tendency for accumulation during once-daily administration. Approximately 80% of an oral dose of omeprazole is excreted in urine as metabolites, and the remainder in feces, primarily via biliary secretion.

With repeated dosing, AUC of omeprazole increases. This increase is dose-dependent and results in a non-linear relationship between dose and AUC after repeated administration. This time- and dose-dependence is related to reduced presystemic metabolism and systemic clearance, possibly due to inhibition of the CYP2C19 enzyme by omeprazole and/or its metabolites (e.g., sulfone).

No metabolite has been found to have any effect on gastric acid secretion.

Special populations

Hepatic impairment

In patients with impaired liver function, omeprazole metabolism is altered, leading to increased AUC. Omeprazole has not shown any tendency toward accumulation with once-daily dosing.

Renal impairment

The pharmacokinetics of omeprazole, including systemic bioavailability and elimination rate, are not altered in patients with reduced renal function.

Elderly patients

Omeprazole metabolism is slightly reduced in elderly patients (75–79 years).

Children

Plasma concentrations similar to those in adults have been achieved in children aged 1 year and older when treated with recommended doses. In children under 6 months of age, omeprazole clearance is low due to limited capacity to metabolize omeprazole.

Clinical characteristics.

Indications.

In adults:

• treatment and prevention of duodenal and benign gastric ulcers, including those associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs);
• eradication of H. pylori in peptic ulcer disease in combination with appropriate antibiotics;
• treatment of gastroesophageal reflux disease, including reflux esophagitis;
• treatment of Zollinger-Ellison syndrome.

In children:

Children aged 1 year and older with body weight over 10 kg:

• treatment of reflux esophagitis;
• symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease.

Children aged 4 years and older:

• treatment of H. pylori-associated duodenal ulcer in combination with antibiotics.

Contraindications.

Hypersensitivity to omeprazole, substituted benzimidazoles, or to any excipient.

Omeprazole, like other proton pump inhibitors, should not be used concomitantly with nelfinavir (see "Interaction with other medicinal products and other types of interactions").

Interaction with other medicinal products and other types of interactions.

Effect of omeprazole on the pharmacokinetics of other active substances

Active substances with pH-dependent absorption

Reduced gastric acidity during omeprazole treatment may affect the absorption of certain drugs.

Nelfinavir, atazanavir

Concomitant administration of omeprazole reduces plasma levels of nelfinavir and atazanavir.

Concomitant use of omeprazole and nelfinavir is contraindicated. Concomitant administration of omeprazole reduces the mean exposure to nelfinavir by approximately 40%; exposure to its pharmacologically active metabolite M8 is reduced by approximately 75–90%. This interaction may also be related to CYP2C19 inhibition.

Concomitant use of omeprazole and atazanavir is not recommended. Concomitant administration of omeprazole (40 mg once daily) with atazanavir/ritonavir complex reduces atazanavir exposure by 75%.

Digoxin

Concomitant administration of omeprazole and digoxin in healthy subjects resulted in a 10% increase in digoxin bioavailability. Isolated reports of digoxin toxicity have been reported. Concomitant use of omeprazole and digoxin in elderly patients should be performed under strict medical supervision.

Clopidogrel

Data on the concomitant use of clopidogrel and omeprazole are conflicting regarding reduced concentrations of clopidogrel's active metabolite.

Other active substances

Absorption of posaconazole, erlotinib, ketoconazole, and itraconazole is significantly reduced; therefore, concomitant use with omeprazole may reduce the clinical efficacy of these agents. Concomitant use of omeprazole with posaconazole and erlotinib should be avoided.

Active substances metabolized via CYP2C19

Omeprazole is a moderate inhibitor of CYP2C19. Thus, metabolism of co-administered active substances metabolized via CYP2C19 may be reduced, and systemic exposure to these substances may increase. Examples include warfarin and other vitamin K antagonists such as cilostazol, diazepam, and phenytoin.

Cilostazol

Omeprazole administered at 40 mg doses to healthy volunteers in a crossover study increased Cmax and AUC of cilostazol by 18% and 26%, respectively, and one of its active metabolites by 29% and 69%, respectively.

Phenytoin

Plasma phenytoin concentrations should be monitored during the first two weeks after initiating omeprazole therapy. If phenytoin dose adjustment is required, monitoring and further dose adjustments should continue after discontinuation of omeprazole.

Saquinavir

Concomitant administration of omeprazole and saquinavir/ritonavir led to an increase in saquinavir plasma levels by approximately 70%, which was well tolerated in HIV-infected patients.

Tacrolimus

Concomitant use of omeprazole and tacrolimus may increase tacrolimus serum levels. Intensified monitoring of tacrolimus concentrations and renal function (creatinine clearance) is recommended, and dose adjustment of tacrolimus may be necessary.

Methotrexate

Elevated methotrexate levels have been reported in some patients receiving concomitant proton pump inhibitors. If high-dose methotrexate is required, temporary discontinuation of omeprazole should be considered.

Effects of other active substances on omeprazole pharmacokinetics

Inhibitors of CYP2C19 and/or CYP3A4

Since omeprazole is metabolized via CYP2C19 and CYP3A4, drugs that inhibit CYP2C19 or CYP3A4 (e.g., clarithromycin and voriconazole) may increase omeprazole serum levels by reducing its metabolic rate. Concomitant use of omeprazole and voriconazole may double omeprazole exposure or even increase it further. Since high doses of omeprazole have been well tolerated, dose adjustment of omeprazole is generally not required. However, dose adjustments should be considered in patients with severe hepatic impairment and during long-term treatment.

Inducers of CYP2C19 and/or CYP3A4

Drugs known to induce CYP2C19 or CYP3A4, or both (e.g., rifampicin and St. John’s wort), may reduce omeprazole serum levels by increasing the rate of omeprazole metabolism.

Special precautions for use.

In the presence of any alarming symptom (e.g., significant unintentional weight loss, recurrent vomiting, dysphagia, hematemesis, or melena), and when gastric ulcer or suspicion thereof exists, malignancy should be ruled out, as treatment with the drug may mask symptoms and delay correct diagnosis.

The use of proton pump inhibitors (PPIs), particularly at high doses and for prolonged periods (>1 year), is associated with a slightly increased risk of fractures of the hip, wrist, and spine, primarily in elderly patients or those with other risk factors. Observational studies suggest that PPIs may increase the overall fracture risk by 10–40%. In some cases, this is related to the presence of other risk factors in the patient. Patients at risk of osteoporosis should receive appropriate treatment and adequate intake of vitamin D and calcium.

Concomitant use of a proton pump inhibitor and atazanavir is not recommended (see section "Interaction with other medicinal products and other forms of interaction"). If a combination of atazanavir with a proton pump inhibitor is necessary, careful clinical monitoring (e.g., viral load) is recommended, along with increasing the atazanavir dose to 400 mg with 100 mg ritonavir; the omeprazole dose should not exceed 20 mg.

Omeprazole, like all acid-suppressing agents, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be considered in patients with vitamin B12 deficiency or those at risk of reduced vitamin B12 absorption during long-term therapy. In individual cases, monitoring plasma vitamin B12 levels may be appropriate. Omeprazole is an inhibitor of CYP2C19. The potential for interaction with drugs metabolized via CYP2C19 should be considered when initiating or discontinuing omeprazole therapy. An interaction has been observed between clopidogrel and omeprazole (see section "Interaction with other medicinal products and other forms of interaction"). The clinical significance of this interaction is unknown. Concomitant use of omeprazole and clopidogrel should be avoided.

In healthy volunteers, a pharmacokinetic/pharmacodynamic interaction between clopidogrel (loading dose 300 mg/daily maintenance dose 75 mg) and omeprazole (80 mg daily orally, i.e., a dose four times higher than the standard daily dose) was observed, resulting in a mean reduction of 46% in exposure to the active metabolite of clopidogrel and a mean reduction of 16% in maximum inhibitory effect (ADP-induced) on platelet aggregation.

In patients taking proton pump inhibitors, including omeprazole, for at least three months, significant hypomagnesemia may occur (in most cases, patients had been taking the drug for about one year). Hypomagnesemia may be suspected based on serious manifestations such as fatigue, tetany, delirium, vertigo, and ventricular arrhythmia. However, it should be noted that in some cases, symptoms may be masked, delaying timely recognition of this complication. In most patients, symptoms of hypomagnesemia resolve and the condition normalizes after administration of magnesium supplements and discontinuation of proton pump inhibitors.

Rare and very rare cases of severe cutaneous adverse reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis, some of which may be life-threatening or fatal, have been reported with omeprazole treatment.

Effect on laboratory tests

Elevated chromogranin A (CgA) levels may interfere with the diagnosis of neuroendocrine tumors. To avoid this interference, omeprazole treatment should be discontinued at least 5 days before measuring CgA (see section "Pharmacological properties"). If, after initial measurement, CgA and gastrin levels have not returned to reference values, the measurement should be repeated 14 days after discontinuation of proton pump inhibitor therapy.

Subacute cutaneous lupus erythematosus (SCLE)

The use of proton pump inhibitors has been associated with very rare cases of SCLE. If skin lesions occur, particularly in sun-exposed areas, and are accompanied by arthralgia, the patient should seek immediate medical attention, and the healthcare provider should consider discontinuing omeprazole. A previous history of SCLE following treatment with a proton pump inhibitor increases the risk of SCLE upon exposure to other proton pump inhibitors.

Renal function impairment

Acute tubulointerstitial nephritis (ATIN) has been observed in patients taking omeprazole. It may occur at any time during omeprazole therapy (see section "Adverse reactions") and may progress to renal failure.

If ATIN is suspected, omeprazole should be discontinued and appropriate treatment initiated immediately.

For the treatment of chronic conditions, the drug should not be used in children for longer than recommended.

Prolonged reduction of gastric acidity may lead to an increase in the number of bacteria present in the gastrointestinal tract.

Treatment with proton pump inhibitors is associated with a slightly increased risk of gastrointestinal infections caused by, for example, Salmonella and Campylobacter, and in hospitalized patients, Clostridium difficile (see section "Pharmacological properties").

As with all long-term treatments, particularly when the treatment period exceeds 1 year, the patient should be under regular medical supervision.

Omeprazole KRKA contains sucrose. Patients with rare hereditary forms of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency should not take Omeprazole KRKA.

Use during pregnancy or breastfeeding.

Research findings indicate no negative effects on pregnancy, fetal health, or newborn infants. Omeprazole may be used during pregnancy if the expected benefit to the mother outweighs the potential risk to the fetus. Omeprazole passes into breast milk in small amounts, but its effect on the infant is unknown; therefore, breastfeeding should be discontinued during treatment with the drug.

Ability to influence reaction speed when driving or operating machinery.

The effect of the drug on the ability to drive or operate machinery is unlikely, but the possibility of adverse reactions such as dizziness and visual disturbances should be considered (see section "Adverse reactions").

Method of Administration and Dosage

Dosage for Adults

Treatment and prevention of duodenal ulcer and benign gastric ulcer, including those associated with use of non-steroidal anti-inflammatory drugs (NSAIDs)

The recommended dose for patients with duodenal ulcer is 20 mg of omeprazole once daily. In most patients, duodenal ulcer heals within 2 weeks. For patients in whom complete healing has not occurred after the initial course, further treatment for 2 weeks is recommended. In severe or recurrent cases, 40 mg of omeprazole daily is recommended, and healing is usually achieved within 4 weeks.

For prevention of recurrence of duodenal ulcer in patients with a negative H. pylori test, the recommended dose is 20 mg of omeprazole once daily. A daily dose of 10 mg may be sufficient for some patients*. In case of inadequate response, the dose may be increased to 40 mg.

For treatment of gastric ulcer, the recommended dose is 20 mg of omeprazole once daily. In most patients, gastric ulcer heals within 4 weeks. Patients who have not completely healed after the initial course are recommended to continue treatment for another 4 weeks. In severe or recurrent cases, 40 mg of omeprazole daily is recommended, with healing usually achieved within 8 weeks.

For prevention of recurrence in patients with gastric ulcer and inadequate response to treatment, the recommended dose is 20 mg of omeprazole once daily. If necessary, the dose may be increased to 40 mg once daily.

For treatment of gastric and duodenal ulcers associated with NSAID use, the recommended dose is 20 mg of omeprazole once daily. In most patients, healing occurs within 4 weeks. Patients who have not completely healed after the initial course are recommended to continue treatment for another 4 weeks.

For prevention of gastric and duodenal ulcers associated with NSAID use in patients at increased risk (age > 60, history of gastric or duodenal ulcers, upper gastrointestinal bleeding), the recommended dose is 20 mg of omeprazole once daily.

Eradication of H. pylori in peptic ulcer disease

When selecting antibiotics for H. pylori eradication, individual drug tolerability should be considered, and compliance with national, regional, and local treatment guidelines and local resistance patterns is essential.

• Omeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1000 mg twice daily for 1 week, or
• Omeprazole 20 mg + clarithromycin 250 mg (if necessary, 500 mg) + metronidazole 400 mg (if necessary, 500 mg, or tinidazole 500 mg) twice daily for 1 week, or
• Omeprazole 40 mg once daily + amoxicillin 500 mg + metronidazole 400 mg (if necessary, 500 mg or tinidazole 500 mg) three times daily for 1 week.

Treatment of gastroesophageal disease, including reflux esophagitis

The recommended dose is 20 mg of omeprazole once daily. In most patients, recovery occurs within 4 weeks. Patients who have not completely recovered after the initial course are recommended to continue treatment for another 4 weeks. For patients with severe esophagitis, 40 mg of omeprazole daily is recommended, with recovery usually achieved within 8 weeks.

For long-term treatment of patients with gastroesophageal reflux disease, the recommended dose is 10 mg* of omeprazole once daily. If necessary, the dose may be increased to 20–40 mg of omeprazole once daily.

For treatment of symptoms of gastroesophageal reflux disease, the recommended dose is 20 mg of omeprazole once daily. A dose of 10 mg may be sufficient for some patients; dosage should be adjusted individually. If the desired effect is not achieved after 4 weeks of treatment with 20 mg of omeprazole daily, the patient should undergo further evaluation.

Treatment of Zollinger-Ellison Syndrome

For patients with Zollinger-Ellison syndrome, dosage should be individualized. Treatment continues until clinical manifestations of the disease resolve. The recommended initial dose is 60 mg of omeprazole once daily. Observations in over 90% of patients with severe disease and inadequate response to other treatments have shown effective maintenance therapy at doses of 20–120 mg daily. Daily doses exceeding 80 mg should be divided and administered in two doses.

Paediatric Dosage

Children aged 1 year and older with body weight ≥ 10 kg

Treatment of reflux esophagitis

Symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease

Dosage recommendations:

Treatment of reflux esophagitis: treatment duration is 4–8 weeks.

Symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease: treatment duration is 2–4 weeks. If the desired effect is not achieved after 2–4 weeks, the patient should be further examined.

Children and adolescents aged 4 years and older

Treatment of duodenal ulcer caused by H. pylori

The choice of appropriate combination therapy should be based on official national, regional, and local guidelines regarding bacterial resistance. The duration of treatment (7 to 14 days) and proper use of antibacterial agents should also be considered.

Treatment should be conducted under medical supervision.

Dosage recommendations:

Special patient groups

Renal impairment

Dose adjustment is not required for patients with renal impairment (see section "Pharmacokinetics").

Hepatic impairment

For patients with hepatic impairment, a daily dose of 10*-20 mg is sufficient (see section "Pharmacokinetics").

Elderly patients (> 65 years of age)

Dose adjustment is not required for elderly patients (see section "Pharmacokinetics").

Method of administration

It is recommended to take Omeprazole KRKA capsules in the morning, preferably before a meal, without damaging the capsule (the capsules should not be chewed or crushed), and with a glass of water.

For patients with swallowing difficulties and for children who can drink or swallow semisolid food

The capsules may be opened and the contents swallowed immediately with half a glass of water, or mixed with a slightly acidic liquid, such as any fruit juice or apple puree, or with unsalted water. This mixture should be taken immediately after preparation or within 30 minutes. The mixture should be shaken before administration and followed by half a glass of water. Milk or carbonated water should not be used.

Alternatively, the capsules may be sucked and then the contents swallowed with half a glass of water. The enteric-coated granules should not be chewed.

* Use omeprazole at appropriate dosage strengths.

Children.

The medicinal product may be used in children aged 1 year and older and weighing more than 10 kg, under medical supervision, for the treatment of reflux esophagitis and symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease, and in children aged 4 years and older for the treatment of duodenal ulcer caused by H. pylori.

Overdose.

Data on the effects of omeprazole overdose in humans are very limited. Doses up to 560 mg of omeprazole have been described in the literature, and there have been single reports of single oral doses reaching 2400 mg of omeprazole (120 times higher than the usual recommended clinical dose). Symptoms reported include nausea, vomiting, dizziness, abdominal pain, diarrhea, and headache. In isolated cases, lethargy, depression, and confusion have also been reported.

The described symptoms are transient in nature. Elimination rate is not altered by increasing the dose. Symptomatic treatment is recommended.

Side effects

The most commonly observed adverse effects of the medicinal product are headache, abdominal pain, constipation, diarrhoea, flatulence, and nausea/vomiting.

Serious skin adverse reactions have been reported with omeprazole treatment, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (see section "Special warnings and precautions for use").

The following adverse reactions have been reported or suspected during clinical trials or post-marketing use of omeprazole. The adverse reactions listed below are classified by organ system or system groups.

Blood and lymphatic system disorders

Leukopenia, thrombocytopenia, agranulocytosis, pancytopenia.

Immune system disorders

Hypersensitivity reactions, such as fever, angioedema, and anaphylactic reaction/shock.

Metabolism and nutrition disorders

Hyponatremia, hypomagnesemia (severe hypomagnesemia may lead to hypocalcemia); hypomagnesemia may also cause hypokalemia, vertigo, microscopic colitis, malaise.

Psychiatric disorders

Insomnia, agitation, confusion, depression, aggression, hallucinations.

Nervous system disorders

Headache, dizziness, paraesthesia, somnolence, taste disturbance.

Eye disorders

Blurred vision.

Ear and labyrinth disorders

Tinnitus.

Respiratory, thoracic and mediastinal disorders

Bronchospasm.

Gastrointestinal disorders

Abdominal pain, constipation, diarrhoea, flatulence, nausea/vomiting, dry mouth, stomatitis, gastrointestinal candidiasis, microscopic colitis, gastric glandular polyps (benign).

Hepatobiliary disorders

Elevated liver enzymes, hepatitis with or without jaundice, hepatic failure, encephalopathy in patients with pre-existing liver disease.

Skin and subcutaneous tissue disorders

Dermatitis, pruritus, rash, urticaria, alopecia, photosensitivity, acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, subacute cutaneous lupus erythematosus.

Musculoskeletal and connective tissue disorders

Fractures of the hip, wrist, or spine, arthralgia, myalgia, muscle weakness.

Renal and urinary disorders

Tubulointerstitial nephritis (with possible progression to renal failure).

Reproductive system and breast disorders

Gynaecomastia.

General disorders

Discomfort, peripheral oedema, increased sweating.

Children

The safety of omeprazole has been evaluated in 310 children aged from 0 to 16 years. Limited data are available on long-term safety studies in 46 children who received maintenance therapy with omeprazole for severe erosive oesophagitis for up to 749 days. The adverse reaction profile is similar to that observed in adults during both short-term and long-term treatment. There are no long-term data on the effects of omeprazole treatment on sexual maturation and growth.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report any suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life

Capsules in blisters: 2 years.

Capsules in bottles: 3 years.

Storage conditions

Store in the original packaging to protect from moisture at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Packaging

7 capsules per blister; 2 or 4 blisters per cardboard box.

14 or 28 capsules in a bottle; 1 bottle per cardboard box.

Prescription status Prescription only.

Manufacturer

KRKA, d.d., Novo mesto, Slovenia.

Manufacturer's address and place of business

Smarjeska cesta 6, 8501 Novo mesto, Slovenia.