Active ingredients: Omeprazole
Nansen 20mg Gastroresistant Capsules
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
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01.0 NAME OF THE MEDICINAL PRODUCT -
NANSEN 20 MG HARD GASTRORESISTANT CAPSULES
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
Each gastro-resistant hard capsule contains:
active principle: omeprazole 20 mg.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Hard capsules containing gastro-resistant granules.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
NANSEN is available exclusively as a 20 mg gastro-resistant hard capsule formulation.
NANSEN gastro-resistant hard capsules are indicated for:
Adults
• Treatment of duodenal ulcers
• Prevention of recurrence of duodenal ulcers
• Treatment of gastric ulcers
• Prevention of recurrence of gastric ulcers
• Eradication of Helicobacter pylori (H. pylori) in peptic ulcer, in association with appropriate antibiotic therapy
• Treatment of gastric and duodenal ulcers associated with the use of NSAIDs
• Prevention of gastric and duodenal ulcers associated with the use of NSAIDs in patients at risk
• Treatment of reflux esophagitis
• Long-term management of patients with healed reflux esophagitis
• Treatment of symptomatic gastroesophageal reflux disease
• Treatment of Zollinger-Ellison syndrome
Pediatric population
Children over 1 year of age and with a body weight ≥ 10 kg
• Treatment of reflux esophagitis
• Symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease
Children and adolescents over 4 years of age
• Treatment of duodenal ulcer caused by H. pylori, in association with antibiotic therapy
04.2 Posology and method of administration -
Dosage
Treatment of duodenal ulcer
The recommended dose in patients with active duodenal ulcer is NANSEN 20 mg once daily. In most patients, ulcer healing is achieved within two weeks of starting treatment. In the case of ulcers that have not completely healed during the first course of treatment, healing is usually achieved during prolonged treatment for another two weeks. In patients with poorly responsive duodenal ulcer NANSEN 40 mg once daily is recommended and healing is usually achieved within four weeks.
Prevention of relapse of duodenal ulcer
For the prevention of duodenal ulcer recurrence in negative patients H. pylori or when the eradication of H. pylori not possible, the recommended dose is NANSEN 20 mg once daily. In some patients a dose of 10 mg may be sufficient. In case of therapeutic failure, the dose can be increased to 40 mg.
Treatment of gastric ulcer
The recommended dose is NANSEN 20 mg once daily. In most patients, healing is achieved within four weeks of starting treatment. In the case of ulcers that have not completely healed after the first course of treatment, healing is usually achieved during prolonged treatment for another four weeks. In patients with ulcers. gastric poorly responsive, once daily administration of NANSEN 40 mg is recommended and healing is generally achieved within eight weeks.
Prevention of relapse in patients with gastric ulcer
For the prevention of relapse in patients with poorly responsive gastric ulcer, the recommended dose is NANSEN 20 mg once daily. If necessary, the dose can be increased to NANSEN 40 mg once daily.
Eradication of H. pylori in peptic ulcer
For the "eradication of"H. pylori, Antibiotic selection must be based on the patient's individual drug tolerance and therapy must be undertaken according to local, regional, national resistance patterns and treatment guidelines.
• NANSEN 20 mg + clarithromycin 500 mg + amoxicillin 1,000 mg, each twice daily for one week, or
• NANSEN 20 mg + clarithromycin 250 mg (alternatively 500 mg) + metronidazole 400 mg (or 500 mg or tinidazole 500 mg), each twice daily for one week, or
• NANSEN 40 mg once daily with amoxicillin 500 mg and metronidazole 400 mg (or 500 mg or tinidazole 500 mg), both three times a day for one week.
For each of the treatment regimens, should the patient still test positive for H. pylori therapy can be repeated.
Treatment of gastric and duodenal ulcers associated with the intake of NSAIDs
For the treatment of NSAID-associated gastric and duodenal ulcers, the recommended dose is NANSEN 20 mg once daily. In most patients, healing is achieved within four weeks of starting treatment. In patients not completely healed after the first course of treatment, healing is usually achieved by extending treatment for another four weeks.
Prevention of gastric and duodenal ulcers associated with the use of NSAIDs in patients at risk
For the prevention of gastric or duodenal ulcers associated with the use of NSAIDs in patients at risk (age> 60, history of gastric and duodenal ulcers, history of upper gastrointestinal bleeding) the recommended dose is NANSEN 20 mg once daily.
Treatment of reflux esophagitis
The recommended dose is NANSEN 20 mg once daily. In most patients, healing is achieved within four weeks of starting treatment. In the case of ulcers that have not completely healed after the first course of treatment, healing is usually achieved by prolonging treatment for another four weeks.
In patients with severe oesophagitis, NANSEN 40 mg once daily is recommended to achieve healing usually within eight weeks.
Long-term management of patients with healed reflux oesophagitis
For the long-term management of patients with healed reflux oesophagitis, the recommended dose is NANSEN 10 mg once daily. If necessary, the dose can be increased to NANSEN 20-40 mg once daily.
Treatment of symptomatic gastroesophageal reflux disease
The recommended dose is NANSEN 20 mg per day. Patients can respond adequately to the 10 mg daily dose, therefore individual dose adjustment should be considered.
If symptomatic control is not achieved after four weeks of treatment with NANSEN 20 mg daily, further investigation is advised.
Treatment of Zollinger-Ellison syndrome
In patients with Zollinger-Ellison syndrome, dosage should be individually adjusted and treatment continued for as long as clinically indicated. The recommended starting dose is NANSEN 60 mg per day. All patients with severe disease who responded poorly to other therapies maintained effective control and control was maintained in more than 90% of patients with NANSEN doses between 20 mg and 120 mg / day. Daily dosages above 80 mg should be divided into two daily administrations
Pediatric population
Children over 1 year of age and with a body weight ≥ 10 kg
Treatment of reflux esophagitis
Symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease
The recommended doses are as follows:
Reflux esophagitis: The treatment period is 4-8 weeks.
Symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease: The treatment lasts 2-4 weeks. If symptomatic control is not achieved after 2-4 weeks, the patient should be further investigated.
Children and adolescents over 4 years of age
Treatment of duodenal ulcer caused by H. pylori
Official local, regional and national guidelines regarding bacterial resistance, duration of treatment (most commonly 7 days, but sometimes up to 14 days) and appropriate use of antibiotics should be considered when selecting the appropriate combination therapy.
The treatment must be carried out under the supervision of a specialist.
The recommended posology is as follows:
Special populations
Impaired renal function
No dosage adjustment is required in patients with impaired renal function (see section 5.2).
Impaired liver function
In patients with impaired hepatic function, a daily dose of 10-20 mg may be sufficient (see section 5.2).
Elderly (> 65 years)
No dosage adjustment is required in elderly patients (see section 5.2).
Method of administration
It is recommended to take NANSEN capsules in the morning, preferably on an empty stomach, swallowed whole with half a glass of water. The capsules should not be chewed or crushed.
For patients with swallowing difficulties and for children who can drink or swallow semi-solid foods
Patients can open the capsule and swallow the contents with half a glass of water, or mixed with slightly acidic liquids such as fruit juice or apple puree or still water. Patients should be advised that in such cases the dispersion should be swallowed immediately (or within 30 minutes) and that it should always be mixed just before drinking. Rinse the bottom with half a glass of water and drink the contents.
Alternatively, patients can dissolve the capsule in the mouth and swallow the contained granules with half a glass of water. The gastro-resistant granules should not be chewed.
04.3 Contraindications -
Hypersensitivity to omeprazole, benzimidazole substitutes or to any of the excipients.
Omeprazole, like other proton pump inhibitors (PPIs), should not be administered concomitantly with nelfinavir (see section 4.5).
04.4 Special warnings and appropriate precautions for use -
In the presence of some alarming symptoms (eg significant unintended weight loss, recurrent vomiting, dysphagia, haematemesis or melaena) and when the presence of a gastric ulcer is suspected or confirmed, the malignant nature of the ulcer should be excluded in how the symptomatic response to therapy could delay a correct diagnosis.
Co-administration of atazanavir and proton pump inhibitors is not recommended (see section 4.5). If the combination of atazanavir and proton pump inhibitor is judged unavoidable, careful clinical monitoring (eg viral load) is recommended in combination with an increase in the dose of atazanavir to 400 mg with 100 mg of ritonavir; the dose of omeprazole it must not exceed 20 mg.
Omeprazole, like all acid-suppressive medicines, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be taken into consideration in patients with low reserves or risk factors for reduced vitamin absorption. B12 in case of long-term therapies.
Omeprazole is a CYP2C19 inhibitor. Potential interaction with drugs metabolised by CYP2C19 should be considered at the initiation or end of treatment with omeprazole. An interaction between clopidogrel and omeprazole has been observed (see section 4.5). The clinical relevance of this interaction is uncertain. As a precaution, concomitant use of clopidogrel and omeprazole should be discouraged.
Interference with laboratory tests
The increased CgA level may interfere with investigations for neuroendocrine tumors. To avoid this interference, omeprazole treatment should be stopped at least five days before the start of CgA measurements (see section 5.1).
Hypomagnesemia
Proton pump inhibitors (PPIs) such as omeprazole have been observed to cause severe hypomagnesaemia in patients treated for at least three months and in many cases for one year.
Serious symptoms of hypomagnesaemia include fatigue, tetany, delirium, convulsions, dizziness, and ventricular arrhythmia. They can initially manifest insidiously and be neglected.
Hypomagnesemia improves in most patients after taking magnesium and discontinuing the proton pump inhibitor.
Healthcare professionals should consider measuring magnesium levels before initiating PPI treatment and periodically during treatment in patients on prolonged therapy or on therapy with digoxin or drugs that can cause hypomagnesaemia (eg diuretics). Severe hypomagnesaemia can produce hypocalcemia.
Subacute cutaneous lupus erythematosus (SCLE)
Proton pump inhibitors are associated with extremely infrequent cases of SCLE. In the presence of lesions, especially on the skin parts exposed to sunlight, and if accompanied by arthralgia, the patient should immediately seek medical attention and the healthcare professional should evaluate the opportunity to discontinue treatment with Nansen. SCLE following treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors.
Proton pump inhibitors, especially when used in high doses and for prolonged periods (> 1 year), may cause a slightly increased risk of hip, wrist and spine fractures, especially in elderly patients or in the presence of other known risk factors. Observational studies suggest that proton pump inhibitors may increase the overall risk of fracture by 10% to 40%. This increase may be partly due to other risk factors. Patients at risk for osteoporosis should receive treatment according to current clinical practice guidelines and must take an "adequate amount of vitamin D and calcium.
Some children with chronic conditions may need long-term treatment although it is not recommended.
Treatment with proton pump inhibitors may cause a slightly increased risk of gastrointestinal infections such as those from Salmonella And Campylobacter (see section 5.1).
As with all long-term treatments, especially if the duration of treatment is greater than 1 year, patients should be monitored regularly.
04.5 Interactions with other medicinal products and other forms of interaction -
Influence of omeprazole on the pharmacokinetics of other active substances
Active ingredients with pH-dependent absorption
Gastric pH-dependent absorption of active substances may be increased or decreased by decreased intragastric acidity during treatment with omeprazole.
Nelfinavir, atazanavir
Plasma levels of nelfinavir and atazanavir decrease when omeprazole is co-administered.
Concomitant administration of omeprazole and nelfinavir is contraindicated (see section 4.3). Co-administration of omeprazole (40 mg once daily) reduced the mean exposure of nelfinavir by approximately 40% and reduced the mean exposure of the pharmacologically active metabolite M8 by approximately 75-90%. The interaction may also involve inhibition of CYP2C19.
Concomitant administration of omeprazole and atazanavir is not recommended (see section 4.4). Co-administration of omeprazole (40 mg once daily) and atazanavir 300 mg / ritonavir 100 mg to healthy volunteers resulted in a 75% reduction in atazanavir exposure. The increase in atazanavir dose to 400 mg did not offset the impact of omeprazole on atazanavir exposure. Co-administration of omeprazole (20 mg once daily) and atazanavir 400 mg / ritonavir 100 mg to healthy volunteers resulted in an approximately 30% reduction in atazanavir exposure compared to atazanavir 300 mg / ritonavir 100 mg once. per day.
Digoxin
Concomitant treatment with omeprazole (20 mg / day) and digoxin in healthy subjects resulted in a 10% increase in the bioavailability of digoxin. Digoxin toxicity has rarely been reported. However, caution is advised in the use of high doses of omeprazole in elderly patients. Therapeutic monitoring of digoxin should therefore be increased.
Clopidogrel
Results from studies in healthy patients demonstrated a "pharmacokinetic (PK) / pharmacodynamic (PD) interaction between clopidogrel (loading dose 300 mg / maintenance dose 75 mg per day) and omeprazole (80 mg po per day), resulting in in a mean decrease of 46% in exposure to the active metabolite of clopidogrel and in a mean decrease of 16% in maximal inhibition (ADP induced) of platelet aggregation.
Diverging data from observational and clinical studies have been reported on the clinical implications of a PK / PD interaction of omeprazole in terms of major cardiovascular events. As a precaution, concomitant use of omeprazole and clopidogrel should be discouraged (see section 4.4).
Other active ingredients
The absorption of posaconazole, erlotinib, ketoconazole and itraconazole is significantly reduced and therefore clinical efficacy may be compromised. Concomitant use of posaconazole and erlotinib should be avoided.
Active substances metabolised by CYP2C19
Omeprazole is a moderate inhibitor of its main metabolising enzyme, CYP2C19. Therefore, the metabolism of concomitant active substances also metabolised by CYP2C19 may be decreased and systemic exposure to these substances increased. Examples of such drugs are R-warfarin and other vitamin K antagonists, cilostazol, diazepam and phenytoin.
Cilostazol
Omeprazole, given at a dose of 40 mg to healthy volunteers in a cross-over study, increased the Cmax and AUC of cilostazol by 18% and 26%, respectively, and of one of its active metabolites by 29% and 69%, respectively. .
Phenytoin
Monitoring of phenytoin plasma concentration is recommended during the first two weeks after starting omeprazole treatment and, if a phenytoin dose adjustment is required, monitoring and further dose adjustment is recommended when ending treatment. with omeprazole.
Mechanism unknown
Saquinavir
Concomitant administration of omeprazole and saquinavir / ritonavir resulted in increased plasma levels of saquinavir up to approximately 70% with good tolerability in HIV-positive patients.
Tacrolimus
Concomitant administration of omeprazole has been reported to increase the serum levels of tacrolimus. Monitoring of tacrolimus concentrations and renal function (creatinine clearance) should be increased and, if necessary, the tacrolimus dosage adjusted.
Methotrexate
When given together with proton pump inhibitors, an increase in methotrexate levels has been reported in some patients. When methotrexate is administered in high doses, a temporary withdrawal of omeprazole may need to be considered.
Influence of other active substances on the pharmacokinetics of omeprazole
CYP2C19 and / or CYP3A4 inhibitors
Since omeprazole is metabolised by CYP2C19 and CYP3A4, active substances inhibiting CYP2C19 or CYP3A4 (such as clarithromycin and voriconazole) may increase the serum levels of omeprazole, decreasing its rate of metabolism. Co-administration of voriconazole results in more than doubled exposure to omeprazole. Since the administration of high doses of omeprazole was well tolerated, no dose adjustment of omeprazole is generally necessary. However, dose adjustment should be made. considered in patients with severe hepatic impairment and in the case of long-term treatment.
Inducers of CYP2C19 and / or CYP3A4
Active substances inducing CYP2C19 or CYP3A4 or both (such as rifampicin and St. John's wort) may cause a decrease in the serum levels of omeprazole, increasing its metabolic rate.
04.6 Pregnancy and breastfeeding -
Pregnancy
The results of three prospective epidemiological studies (more than 1000 exposed patient outcomes) indicate no adverse effects of omeprazole on pregnancy or fetal / newborn health. Omeprazole can be used during pregnancy.
Feeding time
Omeprazole is excreted in breast milk but is unlikely to affect the infant when administered in therapeutic doses.
04.7 Effects on ability to drive and use machines -
It is unlikely that NANSEN will affect the ability to drive or use machines. Adverse drug reactions such as dizziness and visual disturbances may occur (see section 4.8). If they suffer from it, patients should not drive or operate machinery.
04.8 Undesirable effects -
The most common side effects (1-10% of patients) are headache, abdominal pain, constipation, diarrhea, flatulence, nausea / vomiting.
The following adverse reactions, identified or suspected, have been identified during clinical trials with omeprazole and post-marketing. In no case was a correlation with the administered drug dose established. Undesirable effects are classified according to frequency and Organ Classification System (SOC). Frequency categories are defined using the following convention: Very common (≥1 / 10), Common (≥1 / 100 to
SOC / frequency Undesirable effects
Disorders of the blood and lymphatic system
Rare: Leukopenia, thrombocytopenia
Very rare: Agranulocytosis, pancytopenia
Disorders of the immune system
Rare: Hypersensitivity reactions, e.g., fever, angioedema and anaphylactic reaction / shock
Metabolism and nutrition disorders
Rare: Hyponatremia
Not known: Hypomagnesaemia (see section 4.4 Special warnings and precautions for use); hypocalcemia *
Psychiatric disorders
Uncommon: Insomnia
Rare: Agitation, confusion, depression
Very rare: Aggression, hallucinations
Nervous system disorders
Common: Headache
Uncommon: Dizziness, paraesthesia, somnolence
Rare: Changes in taste
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
Rare: Dry mouth, stomatitis, gastrointestinal candidiasis
Not known: Microscopic colitis
Hepatobiliary disorders
Uncommon: Elevation of 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, photosensitization
Very rare: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN)
Frequency "not known": subacute cutaneous lupus erythematosus (see section 4.4).
Musculoskeletal and connective tissue disorders
Uncommon: Fracture of the hip, wrist or spine (see section 4.4 Special warnings and precautions for use)
Rare: Arthralgia, myalgia
Very rare: Muscle weakness
Renal and urinary disorders
Rare: Interstitial nephritis
Diseases of the reproductive system and breast
Very rare: Gynecomastia
General disorders and administration site conditions
Uncommon: Malaise, peripheral edema
Rare: Increased sweating
* hypocalcemia can result from severe hypomagnesaemia.
Pediatric population
The safety of omeprazole was evaluated in a total of 310 children aged 0 to 16 years with acid-related disease. Limited long-term data are available in 46 children who received omeprazole maintenance therapy for up to 749 days in a clinical study in severe erosive esophagitis. The adverse event profile was generally the same as in adults. in both short-term and long-term treatment There are no long-term data regarding the effects of omeprazole treatment on puberty and growth.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions that occur after authorization of the medicine is important as it allows for continuous monitoring of the benefit / risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose -
There is limited information available regarding overdose with omeprazole in humans.
Doses up to 560 mg are reported in the literature and there have been occasional reports of single oral doses up to 2400 mg of omeprazole (120 times the usually recommended clinical dose). Nausea, vomiting, dizziness, abdominal pain, diarrhea and headache have been reported. In individual cases, apathy, depression and confusion were also observed.
The symptoms described were transient and no serious consequences were reported.
With increasing doses the elimination rate did not change (first order kinetics).
Treatment, if necessary, is symptomatic.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: proton pump inhibitor.
ATC code: A02BC01.
Mechanism of action
Omeprazole, a racemic mixture of two active enantiomers, reduces gastric acid secretion by a highly specialized mechanism of action. Omeprazole is a specific inhibitor of proton pumps in the gastric parietal cells.
It acts rapidly and promotes a reversible control of the inhibition of gastric acid secretion with a single daily administration.
Omeprazole is a weak base and is concentrated and converted to the active form in the highly acidic environment of the intracellular canaliculi within the parietal cells, where it inhibits the H +, K + - ATPase - proton pump. This action on the last stage of the hydrochloric acid formation process is dose-dependent and causes a highly effective inhibition of acid secretion, both of the basal and of the stimulated one, regardless of the stimulus used.
Pharmacodynamic effects
All observed pharmacodynamic effects are due to the activity of omeprazole on acid secretion.
Effects on gastric acid secretion
The oral administration of omeprazole once a day allows a rapid and effective inhibition of day and night gastric acid secretion, which reaches its maximum within the first 4 days of treatment.
In patients suffering from duodenal ulcer, the administration of 20 mg of omeprazole maintained an average reduction of 80% in intragastric acidity over 24 hours; 24 hours after the administration of omeprazole, the peak of acid secretion, after stimulation with pentagastrin, is on average reduced by about 70%.
Oral administration of 20 mg of omeprazole maintains the intragastric pH at ≥ 3 for a mean time of 17 hours out of 24 in patients with duodenal ulcer.
As a consequence of reduced acid secretion and intragastric acidity, omeprazole dose-dependently reduces / normalizes acid exposure of the esophagus in patients with gastroesophageal reflux disease.
Inhibition of acid secretion is related to the plasma concentration / time curve (AUC) of omeprazole and not to the actual plasma concentration at a given time.
No tachyphylaxis was observed during treatment with omeprazole.
Effects on Helicobacter pylori
Helicobacter pylori it is associated with peptic acid disease which includes duodenal ulcer disease and gastric ulcer disease.
Helicobacter pylori it is considered the main culprit in the development of gastritis.
Helicobacter pylori together with gastric acid secretion they represent the most important factors for the development of peptic ulcer disease.
Helicobacter pylori it is the main factor in the development of atrophic gastritis which is associated with an increased risk of developing gastric tumors.
The eradication of Helicobacter pylori with omeprazole and antimicrobials it is associated with a "high rate of scarring and long-term remission of peptic ulcers.
The dual therapies studied showed less efficacy than the triple therapies. However, they can be taken into account if known hypersensitivity precludes the use of a triple combination.
Other effects related to acid inhibition
During long-term treatment, an increase in the frequency of appearance of gastric glandular cysts has been observed, which represent the physiological consequence of the pronounced inhibition of acid secretion. These formations are benign and reversible in nature.
The decrease in gastric acidity of any origin, including that due to proton pump inhibitors, increases the gastric bacterial load normally present in the gastrointestinal tract. Treatment with acid-reducing drugs may cause a slightly increased risk of gastrointestinal infections Salmonella and Campylobacter.
During treatment with antisecretory medicinal products, serum gastrin increases in response to decreased acid secretion. Chromogranin A (CgA) also increases due to decreased gastric acidity. The increased level of CgA may interfere with investigations for neuroendocrine tumors. Reports from the literature indicate that treatment with the proton pump inhibitor should be stopped at least five days before the start of CgA measurements. CgA and gastrin are not normalized after 5 days, measurements should be repeated 14 days after stopping omeprazole treatment.
An increase in the number of ECL cells, possibly related to an increase in serum gastrin levels, has been observed in some patients (both children and adults) during long-term treatment with omeprazole.
Pediatric population
In an uncontrolled study with children (1 to 16 years of age) with severe reflux oesophagitis, omeprazole, at doses of 0.7 to 1.4 mg / kg, improved the degree of esophagitis in 90% of cases. and significantly reduced reflux symptoms. In a single-blind study, children aged 0-24 months with clinically diagnosed reflux oesophagitis were treated with 0.5, 1.0 or 1.5 mg omeprazole / kg. The frequency of vomiting / regurgitation episodes decreased by 50% after 8 weeks of treatment, regardless of dose.
Eradication of H. pylori in children
A double-blind, randomized clinical trial (Héliot study) established that omeprazole in combination with two antibiotics (amoxicillin and clarithromycin) is effective and safe in the treatment of H. pylori infection in children aged 4 years and over with gastritis: rate of eradication of the "H. pylori: 74.2% (23/31 patients) with omeprazole + amoxicillin + clarithromycin versus 9.4% (3/32 patients) with amoxicillin + clarithromycin. However, no clinical benefit has been shown with regard to dyspeptic symptoms. This study does not support information for children under the age of 4.
05.2 "Pharmacokinetic properties -
Absorption
Omeprazole and omeprazole magnesium are sensitive to the acid environment, and are therefore administered orally in the form of gastro-resistant granules contained in capsules or tablets.
Absorption of omeprazole is rapid, with maximum plasma levels visible approximately 1-2 hours after dosing. Absorption of omeprazole occurs in the small intestine and is generally completed within 3-6 hours. Concomitant food intake does not affect the bioavailability of the drug. Systemic availability (bioavailability) after a single oral dose of omeprazole is approximately 40%. After repeated daily administrations the bioavailability increases to about 60%.
Distribution
The apparent volume of distribution in healthy subjects is approximately 0.3 l / kg body weight. 97% of omeprazole is bound to plasma proteins.
Biotransformation
Omeprazole is completely metabolised by the cytochrome P450 (CYP) system. Most of the metabolism of omeprazole is dependent on the specific polymorphically expressed CYP2C19 isoform responsible for the formation of hydroxyomeprazole which is the major plasma metabolite. The remainder depends on another specific isoform, CYP3A4, responsible for the formation of omeprazole sulfone. As a consequence of omeprazole's high affinity for CYP2C19, there is a potential for competitive inhibition and drug-drug metabolic interaction between omeprazole and other substrates of CYP2C19. . However, due to its low affinity for CYP3A4, omeprazole does not have the ability to inhibit the metabolism of other CYP3A4 substrates. Furthermore, omeprazole has no inhibitory effect on major CYP enzymes.
Approximately 3% of the Caucasian population and 15-20% of the Asian population have a functional deficiency of the CYP2C19 enzyme, thus being defined as poor metabolisers. In these individuals, the metabolism of omeprazole is probably more catalysed by CYP3A4. After repeated administration. of 20 mg omeprazole once daily, the mean AUC was 5 to 10 times higher in poor metabolisers than in subjects with a functional CYP2C19 enzyme (extensive metabolisers). Maximum plasma concentrations were 3 to 5 times higher. These results have no implications for the posology of omeprazole.
Elimination
The plasma elimination half-life of omeprazole is usually less than one hour after both single and repeated oral once-daily dosing. Omeprazole is completely cleared from the plasma between doses, and therefore there is no tendency for accumulation during once daily administration. Approximately 80% of an oral dose of omeprazole is excreted in the urine as metabolites, the remainder in the faeces originating primarily from biliary secretion.
The AUC of omeprazole increases after repeated administration. This increase is dose-dependent and results in a non-linear dose-AUC relationship after repeated administration. The dependence on time and dose is due to a decrease in first pass metabolism and systemic clearance. probably caused by an inhibition of the CYP2C19 enzyme by omeprazole and / or its metabolites (eg sulphone).
No effect of metabolites on gastric acid secretion was observed.
Special populations
Impaired hepatic function
In patients with hepatic dysfunction, the metabolism of omeprazole is impaired, resulting in an increase in AUC. There was no tendency to accumulate when omeprazole was administered once daily.
Impaired renal function
The pharmacokinetics of omeprazole, including systemic bioavailability and rate of elimination, are not altered in patients with impaired renal function.
Senior citizens
The metabolic rate of omeprazole is slightly reduced in elderly subjects (75-79 years of age).
Pediatric population
During the treatment of children from 1 year of age at recommended doses, plasma concentrations comparable to those in adults were observed. In children less than 6 months of age, the clearance of omeprazole was reduced due to the poor metabolic capacity of omeprazole.
05.3 Preclinical safety data -
Gastric ECL cell hyperplasia and carcinoids were detected in experiments in rats treated for life with omeprazole. These changes are the result of high hypergastrinemia secondary to acid inhibition. Similar observations were obtained following treatment with H2 antagonists, proton pump inhibitors and after partial fundus resection. These changes are therefore not attributable to a direct effect of any single active ingredient.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
NANSEN 20 mg hard gastro-resistant capsules
Each capsule contains the following excipients:
Nucleus : microcrystalline cellulose, low-substituted hydroxypropylcellulose, mannitol, croscarmellose sodium, polysorbate 80, povidone K-30, arginine, sodium lauryl sulfate, glycine, light magnesium carbonate.
Coating : hypromellose, methacrylic acid-ethyl acrylate copolymer, triethyl citrate, sodium hydroxide, titanium dioxide, talc.
Capsule : gelatin, indigo carmine (E-132), titanium dioxide, water.
06.2 Incompatibility "-
Not applicable.
06.3 Period of validity "-
In intact packaging: 2 years.
The expiry date indicated refers to the product in intact and correctly stored packaging.
06.4 Special precautions for storage -
Store at a temperature not exceeding 30 ° C.
Store in the original package to protect the medicine from moisture.
06.5 Nature of the immediate packaging and contents of the package -
PVC-AL-PA / AL-AL blisters; box of 14 capsules.
06.6 Instructions for use and handling -
No special instructions
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
S.F. GROUP Srl - Via Tiburtina, 1143 - 00156 Rome
08.0 MARKETING AUTHORIZATION NUMBER -
NANSEN 20 mg gastro-resistant hard capsules, 14 capsules A.I.C .: 037907019
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
Date of first authorization: 20/12/2007
10.0 DATE OF REVISION OF THE TEXT -
January 2016
