Omeprazole

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

Composition:

Active ingredient: omeprazole,

1 capsule contains: omeprazole pellets containing the active substance, calculated as omeprazole – 20 mg;

Excipients: anhydrous lactose; hypromellose; hydroxypropylcellulose; sodium lauryl sulfate; hypromellose phthalate; sodium hydrogen phosphate, dodecahydrate; diethyl phthalate; sugar spheres (sucrose, corn starch);

capsule shell: azorubine, carmoisine (E 122), titanium dioxide (E 171), gelatin.

Pharmaceutical form. Capsules.

Main physicochemical properties: hard gelatin capsules size 2, body pale pink, cap bright pink. The capsule contents are white or almost white spherical pellets.

Pharmacotherapeutic group

Drugs for treatment of peptic ulcer and gastroesophageal reflux disease. Proton pump inhibitors. ATC code A02BC01.

Pharmacological Properties

Pharmacodynamics

Omeprazole is a specific inhibitor of the proton pump in parietal cells. As a result, it inhibits gastric secretion of hydrochloric acid. The inhibitory effect on acid secretion is reversible. Omeprazole is a weak base that accumulates and is converted into its active form in the acidic environment of parietal cells, where it inhibits H⁺, K⁺-ATPase, thus affecting the final stage of gastric acid secretion.

Inhibition of acid secretion is dose-dependent and affects both basal and stimulated acid secretion, regardless of the type of stimulation. Omeprazole does not affect cholinergic or histaminergic receptors. As with treatment using H₂-receptor blockers, omeprazole therapy leads to reduced gastric acidity and, consequently, a proportional increase in gastrin levels. The increase in gastrin levels is reversible. During prolonged treatment, an increase in the number of glandular cysts in the stomach may occur. These changes are physiological, resulting from decreased acidity, are benign, and reversible. Reduction of gastric acidity by proton pump inhibitors or other acid-suppressing agents may lead to an increase in the number of bacteria present in the gastrointestinal tract. Therefore, such treatment increases the risk of gastrointestinal infections caused by Salmonella, Campylobacter, and Clostridium difficile in hospitalized patients.

The effect on acid secretion is directly proportional to the area under the concentration-time curve (AUC) and does not depend on omeprazole plasma concentration.

Omeprazole exerts a bactericidal effect on Helicobacter pylori. Eradication of H. pylori with concomitant use of omeprazole and antibiotics enables rapid suppression of disease symptoms, achieves a high rate of mucosal healing, and provides sustained long-term remission, reducing the likelihood of gastrointestinal bleeding.

In reflux esophagitis, normalization of acid exposure in the esophagus and maintenance of intragastric pH > 4 for 24 hours, along with reduced destructive properties of gastric contents (inhibition of pepsinogen conversion to pepsin), promotes symptom relief and complete healing of esophageal lesions (healing rates exceed 90%). Omeprazole is highly effective in treating severe and complicated forms of erosive and ulcerative esophagitis resistant to histamine H₂-receptor blockers. Long-term maintenance therapy prevents relapses of reflux esophagitis and reduces the risk of complications.

Pharmacokinetics

The active substance, omeprazole, in the form of microgranules, is contained within an enteric coating. After oral administration, the drug is rapidly and extensively absorbed from the gastrointestinal tract; however, bioavailability does not exceed 50–55% (first-pass effect in the liver). Plasma protein binding (to albumin and alpha₁-acid glycoprotein) is very high—approximately 95%.

After a single 20 mg dose of omeprazole, inhibition of gastric secretion begins within the first hour, reaches maximum effect within 2 hours, and lasts for approximately 24 hours. The extent of effect depends on the dose. The ability of parietal cells to produce hydrochloric acid recovers within 3–5 days after discontinuation of therapy.

Distribution

The volume of distribution in healthy volunteers is 0.3 L/kg, which corresponds to that observed in patients with renal insufficiency. In elderly patients and patients with hepatic insufficiency, the volume of distribution may be slightly reduced. Omeprazole is approximately 95% bound to plasma proteins.

Metabolism and Elimination

Omeprazole is completely metabolized by the cytochrome P450 (CYP) system. The major part of its metabolism depends on the polymorphically expressed CYP2C19, responsible for the formation of hydroxyomeprazole, the main metabolite in plasma. The remainder depends on another specific isoenzyme, CYP3A4, responsible for the formation of omeprazole sulfone. Due to omeprazole's high affinity for CYP2C19, there is potential for competitive inhibition and metabolic interaction with other CYP2C19 substrates. However, due to its low affinity for CYP3A4, omeprazole does not have the ability to inhibit the metabolism of other CYP3A4 substrates.

The pharmacokinetic parameters described below primarily reflect data in individuals with functional CYP2C19 enzyme activity—so-called "rapid metabolizers."

The drug is transformed in the liver to form at least six metabolites, which are practically devoid of antisecretory activity.

Excretion occurs mainly via the kidneys as metabolites (72–80%) and through the intestine (18–23%). The elimination half-life is 0.5–1 hour (with normal liver function) or 3 hours (in chronic liver disease).

Total plasma clearance is 30–40 L/h after a single dose. The elimination half-life of omeprazole is usually less than 1 hour, both after single and repeated daily oral administration. The AUC of omeprazole increases with repeated dosing. This increase is dose-dependent and results in a nonlinear relationship between AUC and dose upon repeated administration. This time- and dose-dependent relationship is attributed to reduced presystemic metabolism and systemic clearance, possibly due to inhibition of the CYP2C19 enzyme by omeprazole and/or its metabolites (e.g., sulfone). Omeprazole is completely cleared from plasma between doses, with no tendency for accumulation when administered once daily.

No effect of metabolites on gastric acid secretion has been observed. Approximately 80% of the orally administered dose of omeprazole is excreted in urine as metabolites, and the remainder in feces, primarily via biliary secretion.

Poor metabolizers: Approximately 3% of the European population and 15% of the Asian population have a deficiency of the CYP2C19 enzyme and are classified as "poor metabolizers." In these individuals, omeprazole metabolism may be catalyzed by CYP3A4. After repeated administration of omeprazole 20 mg once daily, the mean AUC in these patients increases 5–10 times compared to individuals with normal CYP2C19 activity (rapid metabolizers). Mean peak plasma concentrations are also 3–5 times higher. However, these findings do not affect omeprazole dosing recommendations.

Patients with hepatic impairment: Omeprazole metabolism is impaired in patients with liver dysfunction, leading to increased AUC. However, with once-daily dosing, no tendency toward omeprazole accumulation has been observed.

Patients with renal impairment: The pharmacokinetics of omeprazole, including systemic bioavailability and elimination rate, remain unchanged in patients with renal impairment.

Elderly patients: The rate of metabolism is slightly reduced in elderly patients (75–79 years of age).

Clinical Characteristics

Indications

Adults

• Treatment of duodenal ulcer;
• prevention of recurrence of duodenal ulcer;
• treatment of gastric ulcer;
• prevention of recurrence of gastric ulcer;
• use in combination with appropriate antibiotics for eradication of Helicobacter pylori in peptic ulcer;
• treatment of gastric and duodenal ulcer associated with use of nonsteroidal anti-inflammatory drugs (NSAIDs);
• prevention of gastric and duodenal ulcer associated with use of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients at risk;
• treatment of reflux esophagitis;
• long-term treatment of patients with healed reflux esophagitis;
• symptomatic treatment of gastroesophageal reflux disease (GERD);
• treatment of Zollinger-Ellison syndrome.

Children

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.

Children aged 4 years and older:

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

Contraindications

Hypersensitivity to omeprazole, substituted benzimidazoles, or to any of the excipients.

Omeprazole, like other proton pump inhibitors (PPIs), should not be used concomitantly with nelfinavir.

Interaction with other medicinal products and other forms of interaction

Effect of omeprazole on the pharmacokinetics of other medicinal products

Medicinal products whose absorption is pH-dependent. Reduced gastric acidity during omeprazole treatment may increase or decrease absorption of medicinal products whose absorption depends on gastric pH.

Other medicinal products. As with other medicinal products that suppress gastric acidity, absorption, and thus clinical efficacy, of such medicinal products as posaconazole, erlotinib, ketoconazole, itraconazole, may be reduced during omeprazole treatment. Concomitant use of omeprazole with posaconazole and erlotinib should be avoided.

Nelfinavir, atazanavir. Plasma concentrations of nelfinavir and atazanavir are reduced when these medicinal products are used concomitantly with omeprazole. Concomitant use of omeprazole and nelfinavir is contraindicated. Concomitant use of omeprazole (40 mg once daily) reduced the mean exposure to nelfinavir by approximately 40%, and the mean exposure to its pharmacologically active metabolite M8 decreased by approximately 75–90%. The interaction may also involve inhibition of CYP2C19. As a result of concomitant administration of omeprazole (40 mg once daily) with atazanavir 300 mg/ritonavir 100 mg in healthy volunteers, exposure to atazanavir decreased by 75%. Increasing the atazanavir dose to 400 mg does not compensate for the effect of omeprazole on atazanavir exposure. In healthy volunteers, concomitant administration of omeprazole (20 mg once daily) with atazanavir 400 mg/ritonavir 100 mg resulted in a 30% reduction in atazanavir exposure compared to administration of atazanavir 300 mg/ritonavir 100 mg.

Digoxin. Concomitant treatment with omeprazole (20 mg daily) and digoxin increases bioavailability of digoxin by 10%. Cases of digoxin toxicity have been reported rarely. However, caution should be exercised when prescribing high doses of omeprazole to elderly patients. Therapeutic monitoring of digoxin saturation should be intensified.

Clopidogrel. Concomitant use of omeprazole and clopidogrel should be avoided.

In healthy volunteers, a pharmacokinetic (PK)/pharmacodynamic (PD) interaction between clopidogrel (loading dose 300 mg/daily maintenance dose 75 mg) and omeprazole (80 mg daily orally) was observed, resulting in a mean reduction of 46% in AUC of the active metabolite of clopidogrel and a mean reduction of 16% in maximum inhibitory effect (ADP [adenosine diphosphate]-induced) on platelet aggregation.

Data from observational and clinical studies on the clinical implications of this PK/PD interaction regarding major cardiovascular events are conflicting. As a precautionary measure, concomitant use of omeprazole and clopidogrel should be avoided.

Medicinal products metabolized by CYP2C19. Omeprazole inhibits CYP2C19, the main enzyme involved in omeprazole metabolism.

Thus, metabolism of concomitantly administered medicinal products that are also metabolized by CYP2C19 may be reduced, and systemic exposure to these agents may increase. Examples include R-warfarin and other vitamin K antagonists, cilostazol, diazepam, and phenytoin.

Cilostazol. Data indicate that administration of 40 mg omeprazole increases Cmax and AUC of cilostazol by 18% and 26%, respectively, and Cmax and AUC of one of its active metabolites by 29% and 69%, respectively.

Phenytoin. Monitoring of phenytoin plasma concentrations is recommended during the first two weeks after initiation of omeprazole treatment; and if phenytoin dosage adjustment has been made, monitoring and further dosage adjustment should be performed after discontinuation of omeprazole treatment.

Interactions with unknown mechanisms

Tacrolimus. Data indicate that concomitant use of omeprazole increases serum levels of tacrolimus. Intensified monitoring of tacrolimus levels and renal function (creatinine clearance) is required, and dosage adjustment of tacrolimus should be considered if necessary.

Methotrexate. Data are available on increased methotrexate levels in some patients when co-administered with proton pump inhibitors. If high-dose methotrexate therapy is required, consideration should be given to temporarily discontinuing omeprazole.

Saquinavir. Concomitant use of omeprazole with saquinavir/ritonavir resulted in an increase in saquinavir plasma levels by approximately 70%, which was well tolerated by HIV-infected patients.

Effect of other medicinal products on the pharmacokinetics of omeprazole

Inhibitors of CYP2C19 and CYP3A4. Since omeprazole is metabolized by CYP2C19 and CYP3A4, medicinal products that inhibit CYP2C19, CYP3A4, or both enzymes (such as clarithromycin and voriconazole) may cause increased omeprazole serum levels by slowing its metabolism. Concomitant use of voriconazole may lead to more than a twofold increase in omeprazole exposure. Since high doses of omeprazole are generally well tolerated, dose adjustment is not required during short-term concomitant use. However, dose adjustment should be considered in patients with severe hepatic impairment and in cases where long-term treatment is indicated.

Inducers of CYP2C19 and CYP3A4. Medicinal products that induce CYP2C19, CYP3A4, or both enzymes (such as rifampicin, St. John’s wort) may cause decreased omeprazole serum levels by accelerating its metabolism.

Special precautions for use.

In the presence of any alarming symptom (e.g., obvious weight loss, recurrent vomiting, dysphagia, hematemesis, or melena) and in suspected or confirmed gastric ulcer, malignancy must be ruled out, since treatment may reduce symptom severity and delay diagnosis.

Concomitant use of atazanavir with proton pump inhibitors (PPIs) is not recommended. If co-administration of atazanavir with PPIs cannot be avoided, careful clinical monitoring (e.g., viral load) is recommended, together with an increased dose of atazanavir to 400 mg with 100 mg ritonavir; the dose of omeprazole should not exceed 20 mg.

Omeprazole, like all medicinal products that suppress gastric acid secretion, may reduce absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be considered in patients with cachexia or risk factors for reduced vitamin B12 absorption during long-term therapy.

Omeprazole is an inhibitor of CYP2C19. At the beginning or end of omeprazole treatment, potential interactions with medicinal products metabolized by CYP2C19 should be considered. An interaction has been observed between clopidogrel and omeprazole. The clinical significance of this interaction is not established. As a precautionary measure, concomitant use of omeprazole and clopidogrel should be avoided.

Severe hypomagnesemia has been reported in patients receiving proton pump inhibitors (PPIs), such as omeprazole, for at least 3 months, and in most cases, the patients had been taking the drug for about 1 year.

Hypomagnesemia may be suspected based on such serious manifestations as fatigue, tetany, seizures, delirium, dizziness, and ventricular arrhythmias. 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 levels normalize after magnesium supplementation and discontinuation of proton pump inhibitors.

In patients requiring long-term use of proton pump inhibitors, and in patients concomitantly taking digoxin or other medicinal products that may cause hypomagnesemia (e.g., diuretics), magnesium levels should be checked before starting treatment and periodically during treatment.

Rarely and very rarely, severe cutaneous adverse reactions (SCARs) have been reported with omeprazole treatment, including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), which may be life-threatening or fatal.

The use of proton pump inhibitors, particularly at high doses and for prolonged periods (>1 year), slightly increases the risk of fractures of the hip, wrist, and spine, primarily in elderly patients or in the presence of other identified risk factors. Observational studies suggest that proton pump inhibitors increase the overall fracture risk by 10–40%. In some cases, this is associated with 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.

Subacute cutaneous lupus erythematosus (SCLE)

The use of proton pump inhibitors may occasionally induce subacute cutaneous lupus erythematosus. If skin manifestations occur, especially in sun-exposed areas and accompanied by arthralgia, patients should immediately consult a physician and discontinuation of omeprazole should be considered. A history of subacute cutaneous lupus erythematosus following PPI use increases the risk of developing SCLE when other proton pump inhibitors are used.

Renal function impairment

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

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

Effect on laboratory test results

Omeprazole use may increase chromogranin A (CgA) levels. Elevated CgA levels may interfere with diagnostic tests for neuroendocrine tumors. Therefore, omeprazole should be temporarily discontinued at least 5 days before CgA measurement (see section "Pharmacological properties"). If CgA and gastrin levels have not returned to reference ranges after initial measurements, these parameters should be re-measured 14 days after discontinuation of PPI therapy.

In some cases, treatment of chronic diseases in children may require longer-term use of the drug, although this is not recommended.

The medicinal product contains sucrose (in the sugar spheres) as an excipient; therefore, it should not be used in patients with rare hereditary forms of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency.

The medicinal product contains lactose as an excipient; therefore, it should not be used in patients with galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.

The medicinal product contains carmoisine (E 122), which may cause allergic reactions.

Treatment with proton pump inhibitors slightly increases the risk of gastrointestinal infections caused by Salmonella and Campylobacter, and in hospitalized patients, possibly also by Clostridium difficile (see section "Pharmacological properties").

As with any long-term treatment, especially if duration exceeds 1 year, the patient's condition should be monitored regularly.

Omeprazole contains less than 1 mmol of sodium (23 mg) per capsule; thus, this medicinal product is considered "sodium-free."

Use during pregnancy or breastfeeding

Pregnancy

Results from three prospective epidemiological studies (over 1000 observed outcomes) indicate no adverse effects of omeprazole on pregnancy or on fetal/neonatal health. Omeprazole may be used during pregnancy.

Breastfeeding

Omeprazole passes into breast milk, but the likelihood of effects on the infant is low when used at therapeutic doses.

Fertility

Oral administration of racemic omeprazole in animal studies did not affect reproductive function.

Ability to influence reaction speed when driving or operating machinery

It is unlikely that omeprazole affects the ability to drive or operate machinery. However, adverse reactions such as dizziness and visual disturbances may occur. If such disorders occur, patients should not drive or operate machinery.

Method of Administration and Dosage

Adults

Duodenal Ulcer Treatment

The recommended dose for patients with active duodenal ulcer is 20 mg of omeprazole once daily. Healing occurs within two weeks in most patients. For patients who have not healed completely after the initial treatment course, an additional 2 weeks of therapy is recommended. For patients with refractory duodenal ulcer, 40 mg of omeprazole daily is recommended; healing usually occurs within 4 weeks.

Prevention of Recurrence of Duodenal Ulcer

For prevention of recurrence of duodenal ulcer in patients with a negative H. pylori test or when eradication of H. pylori is not possible, the recommended dose is 20 mg of omeprazole once daily. A daily dose of 10 mg may be sufficient for some patients (if a 10 mg dose is required, use a medicinal product containing "omeprazole" in the appropriate dosage). If therapeutic response is inadequate, the dose may be increased to 40 mg.

Gastric Ulcer Treatment

The recommended dose is 20 mg of omeprazole once daily. Healing occurs within four weeks in most patients. For patients who have not healed completely after the initial course, healing usually occurs during the subsequent four weeks of treatment. For patients with refractory gastric ulcer, 40 mg of omeprazole daily is recommended; healing occurs within 8 weeks.

Prevention of Recurrence of Gastric Ulcer

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.

H. pylori Eradication in Peptic Ulcer Disease

When selecting antibiotics for H. pylori eradication, individual drug tolerability should be considered, and adherence to national, regional, and local treatment guidelines and recommendations is essential.

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

If H. pylori remains positive in the patient, therapy may be repeated after each of these regimens.

Treatment of NSAID-Associated Gastric and Duodenal Ulcers

For treatment of gastric and duodenal ulcers associated with use of nonsteroidal anti-inflammatory drugs (NSAIDs), the recommended dose is 20 mg of omeprazole once daily. Healing occurs within 4 weeks in most patients. For patients who have not healed completely after the initial course, an additional 4 weeks of therapy is recommended.

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

Reflux Esophagitis Treatment

The recommended dose is 20 mg of omeprazole once daily. Recovery occurs within 4 weeks in most patients. For patients who have not fully recovered after the initial course, an additional 4 weeks of therapy is recommended. For patients with severe esophagitis, 40 mg of omeprazole daily is recommended, with recovery usually achieved within 8 weeks.

Long-Term Management of Patients with Healed Reflux Esophagitis

For long-term management of patients with healed reflux esophagitis, the recommended dose is 10 mg of omeprazole once daily (if a 10 mg dose is required, use a medicinal product containing "omeprazole" in the appropriate dosage). If necessary, the dose may be increased to 20–40 mg of omeprazole once daily.

Treatment of Symptomatic Gastroesophageal Reflux Disease (GERD)

The recommended dose is 20 mg of omeprazole once daily. Some patients may respond adequately to 10 mg daily (if a 10 mg dose is required, use a medicinal product containing "omeprazole" in the appropriate dosage); therefore, the dose should be adjusted individually.

If the desired outcome is not achieved after 4 weeks of treatment with 20 mg omeprazole daily, the patient should undergo further evaluation.

Zollinger-Ellison Syndrome Treatment

For patients with Zollinger-Ellison syndrome, dosage should be individually adjusted. Treatment continues until clinical symptoms 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 efficacy of maintenance therapy with doses of 20–120 mg daily. Daily doses exceeding 80 mg should be divided and administered in two doses.

Dosage for Children

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

Reflux Esophagitis Treatment

Symptomatic Treatment of Heartburn and Acid Regurgitation in Gastroesophageal Reflux Disease (GERD)

Dosage recommendations:

* If necessary, use the 10 mg dose strength of the medicinal product.

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 response is not achieved after 2–4 weeks, the patient should be further investigated.

Children from 4 years of age and adolescents

Treatment of duodenal ulcer caused by H. pylori

The choice of appropriate combination therapy should take into account official national, regional, and local guidelines regarding bacterial resistance. The duration of treatment (usually 7 days, but sometimes up to 14 days) and the correct administration of antibacterial agents should also be considered.

Treatment should be conducted under medical supervision.

Dosage recommendations:

* If a dose of 10 mg is required, administer the medicinal product in the appropriate dosage strength.

Special patient groups

Renal impairment

Dose adjustment is not required in patients with impaired renal function (see section "Pharmacokinetics").

Hepatic impairment

In patients with impaired liver function, a daily dose of 10*–20 mg is sufficient (if a dose of 10 mg is required, use a medicinal product containing the active substance "omeprazole" in the appropriate dosage strength) (see section "Pharmacokinetics").

Elderly patients

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

Method of administration

It is recommended to take omeprazole capsules in the morning, swallowing them whole (capsules should not be chewed or crushed), with half a glass of water.

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

Capsules may be opened and the contents swallowed directly with half a glass of water, or mixed with a weakly acidic liquid such as any fruit juice or apple puree, or with still water. This mixture must be consumed within 30 minutes after preparation. Before administration, the mixture should be shaken and followed by half a glass of water.

Alternatively, the capsule may be sucked first, then the contents swallowed with half a glass of water. Granules with enteric coating must not be chewed.

Children. Omeprazole is indicated for children aged 1 year and older with body weight above 10 kg, prescribed by a physician, for reflux esophagitis, and for symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease; for children aged 4 years and older – for treatment of H. pylori-associated duodenal ulcer under medical supervision.

Overdose

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

However, all reported symptoms were transient, and no serious consequences were reported. The elimination rate of the drug was not altered (first-order kinetics) with increasing dose. Symptomatic treatment may be required.

Adverse Reactions

The most common adverse reactions (1–10% of patients) are headache, abdominal pain, constipation, diarrhea, flatulence, and nausea/vomiting.

Serious skin adverse reactions (SSARs) have been reported during omeprazole treatment, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) (see section "Special Warnings").

The adverse reactions listed below have been identified or suspected during clinical trials or post-marketing use of omeprazole. These were found not to be dose-dependent. Adverse reactions are categorized by organ systems. Frequency is defined as follows: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10000, < 1/1000); very rare (< 1/10000); frequency not known (cannot be estimated from available data).

Blood and lymphatic system disorders:
Rare: leukopenia, thrombocytopenia;
Very rare: agranulocytosis, pancytopenia.

Immune system disorders:
Rare: hypersensitivity reactions, including fever, angioedema, and anaphylactic reactions/shock.

Metabolism and nutrition disorders:
Rare: hyponatremia;
Frequency not known: hypomagnesemia. Severe hypomagnesemia may lead to hypocalcemia; hypomagnesemia may also cause hypokalemia.

Psychiatric disorders:
Uncommon: insomnia;
Rare: agitation, confusion, depression;
Very rare: aggression, hallucinations.

Nervous system disorders:
Common: headache;
Uncommon: dizziness, paraesthesia, somnolence;
Rare: taste disturbance.

Eye disorders:
Rare: blurred vision.

Ear and labyrinth disorders:
Uncommon: vertigo.

Respiratory, thoracic and mediastinal disorders:
Rare: bronchospasm.

Gastrointestinal disorders:
Common: abdominal pain, constipation, diarrhea, flatulence, nausea/vomiting, fundic gland polyps (benign);
Rare: dry mouth, stomatitis, gastrointestinal candidiasis;
Frequency not known: microscopic colitis.

Hepatobiliary disorders:
Uncommon: increased liver enzymes;
Rare: hepatitis with or without jaundice;
Very rare: hepatic failure, encephalopathy in patients with pre-existing liver disease.

Skin and subcutaneous tissue disorders:
Uncommon: dermatitis, pruritus, rash, urticaria;
Rare: alopecia, photosensitivity, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP);
Very rare: erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN);
Frequency not known: subacute cutaneous lupus erythematosus.

Musculoskeletal and connective tissue disorders:
Uncommon: fracture of hip, wrist, or spine;
Rare: arthralgia, myalgia;
Very rare: muscle weakness.

Renal and urinary disorders:
Rare: tubulointerstitial nephritis (with possible progression to renal failure).

Reproductive system and breast disorders:
Very rare: gynecomastia.

General disorders:
Uncommon: malaise, peripheral edema;
Rare: increased sweating.

Children

The safety of omeprazole has been evaluated in 310 children aged 0 to 16 years with acid-related disorders. There are also some long-term safety data from 46 children who received maintenance therapy with omeprazole for the treatment of severe erosive esophagitis over 749 days. The adverse reaction profile is similar to that in adults during both short- and long-term treatment. There are no long-term observational data on the effects of omeprazole on growth and sexual maturation.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare professionals, pharmacists, patients, and their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy through the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life: 3 years.

Storage conditions:
Store in the original packaging at a temperature not exceeding 25 °C. Keep out of the reach of children.

Packaging:
10 capsules per blister, 1 or 3 blisters per carton.

Prescription status: Prescription only.

Manufacturer: JSC "Kyivmedpreparat".

Manufacturer's address and place of business:
139 Saksahanskoho Street, Kyiv, 01032, Ukraine.