Omeprazole 10mg Gastro-Resistant Capsules
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Omeprazole 10 mg gastro-resistant capsule.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Omeprazole 10 mg Capsule:
Each gastro-resistant capsule contains 10 mg of omeprazole.
For excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Gastro-resistant capsule, hard
Omeprazole 10 mg Capsule: Opaque yellow and opaque white capsule, with imprint "10 mg".
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
• Treatment and prevention of relapse of reflux oesophagitis
• Eradication of Helicobacter pylori in patients with associated peptic ulcers, in combination with appropriate antibacterial regimens (see section 4.2)
• Treatment and prevention of recurrence of duodenal ulcers
• Treatment of benign gastric ulcers
• Zollinger-Ellison syndrome
Treatment of NSAID (Non Steroid Anti Inflammatory Drug) related gastric and duodenal ulcers. Prevention of relapse of NSAID related gastric and duodenal is restricted to patients with a previous history of these conditions
4.2 Posology and method of administration
Reflux oesophagitis:
Treatment of reflux oesophagitis: The usual dose is 20 mg once daily. The duration of treatment is 4-8 weeks. In severe/recurrent cases the dose of omeprazole can be increased to 40 mg once daily.
Maintenance treatment of reflux oesophagitis to prevent relapse: The usual daily dose is 10 to 20 mg depending on clinical response.
Children above 2 years and adolescents with severe reflux oesophagitis:
As clinical experience in children is limited, omeprazole should only be used in children with severe reflux oesophagitis resistant to other therapeutic measures and treatment should be initiated by a hospital based paediatrician.
Continuous pH measurement and genotyping (concerning CYP 2C19 status) may be performed if appropriate for optimal therapeutic response.
The following dosage (equivalent to about 1 mg/kg/day) should be used: Weight 10 kg to 20 kg: 10 mg/day Weight over 20 kg: 20 mg/day
Treatment duration is usually 4 to 8 weeks and should not exceed 12 weeks due to lack of data with long-term use in this age group.
Symptomatic treatment of gastroesophageal reflux disease:
The usual dose is 10 to 20 daily mg depending on clinical response. The treatment duration is 2 to 4 weeks.
If the patient does not experience any improvement in symptoms after a 2 week treatment further examinations should be performed.
Eradication therapy:
Patients with peptic ulcers due to Helicobacter pylori infection should be treated with eradication therapy with appropriate combinations of antibiotics with adequate dosing regimens. The selection of an appropriate regimen should be based on patient tolerability and therapeutic guidelines. Omeprazole 20 mg plus 2 antibiotics twice daily for 1 week has been used eg - Omeprazole 20 mg, Amoxicillin 1000 mg, Clarithromycin 500 mg all 2 times daily: Omeprazole 20 mg, Clarithromycin 250 mg, Metronidazole 400-500 mg all 2 times daily (see section 5.1)
To avoid the development of resistance the treatment duration should not be reduced.
Combination therapy including metronidazole should not be considered as first choice because of the carcinogenic potential of metronidazole and, if used, the treatment should be restricted to less than 10 days.
In patients with active ulcers an extension of the therapy with omeprazole-monotherapy according to the posology and treatment duration given below may be performed.
Duodenal and gastric ulcers
Omeprazole monotherapy is only for use if eradication therapy is not indicated or has been unsuccessful (i.e. ulcers still active after adequate eradication regimen).
Treatment of duodenal ulcers: The usual dose is 20 mg once daily. The duration of the treatment is 2-4 weeks.
Prevention of recurrence of duodenal ulcers: 10 mg once daily.
Treatment of benign gastric ulcers: The usual dose is 20 mg once daily. The duration of the treatment is 4-8 weeks.
In severe/recurrent cases of duodenal and gastric ulcers the dose of omeprazole can be increased to 40 mg once daily.
NSAID related gastric and duodenal ulcers:
Treatment of NSAID related gastric and duodenal ulcers: The usual dose is 20 mg daily. The treatment duration is 4-8 weeks.
Maintenance treatment of NSAID related gastric and duodenal ulcers to prevent relapse in patients with a history of these conditions: The usual dose is 20 mg daily.
Zollinger-Ellison syndrome:
The dosage should be adjusted individually and continued under specialist supervision as long as clinically indicated. The recommended initial dosage is 60 mg once daily. Doses above 80 mg daily should be divided and given twice daily. In patients with Zollinger-Ellison syndrome the treatment is not subject to a time limit.
Elderly:
Dose adjustment is not required in the elderly Children:
Omeprazole should not be used in children under 2 years of age (see section 4.3).
Impaired renal function:
Dose adjustment is not required in patients with impaired renal function. Impaired hepatic function:
As bioavailability and half-life can increase in patients with impaired hepatic function, the dose requires adjustment with a maximum daily dose of 20 mg.
Method of administration:
The capsules should be swallowed whole with sufficient fluid. The capsules should not be chewed or milled. In patients with swallowing difficulties, the capsules may be opened and the contents swallowed alone or suspended in a small amount of fruit juice or yoghurt after gentle mixing.
4.3 Contraindications
Omeprazole is contraindicated in patients with hypersensitivity to omeprazole or to any of the excipients.
Children under 2 years of age.
Concomitant use with St. Johns wort or atazanavir sulphate (See section 4.5).
Combination therapy with clarithromycin should not be used in patients with hepatic impairment (See section 4.5).
4.4. Special warnings and precautions for use
Prior to initiating treatment
In patients with peptic ulcer disease Helicobacterpylori-status should be determined if relevant. In patients who are shown to be Helicobacter pylori-positive, the elimination of the bacterium by eradication therapy should be the primary aim wherever possible.
If a gastric ulcer is suspected, the possibility of malignancy must be excluded before treatment with omeprazole is instituted, as treatment may alleviate symptoms and delay diagnosis.
The diagnosis of reflux oesophagitis should be confirmed endoscopically.
Risk of GI infections
Decreased gastric acidity-increases gastric counts of bacteria normally present in the gastro-intestinal tract. Treatment with acid-reducing medicinal products leads to a slightly increased risk of gastrointestinal infections, such as Salmonella and Campylobacter.
Patients with impaired hepatic or renal function
In patients with severe impaired hepatic function, liver enzyme values should be checked periodically during treatment with omeprazole.
During combination treatment caution should be exercised in patients with renal or hepatic dysfunction (for dose restriction see 4.2). Use with clarithromycin is contra-indicated in patients with hepatic impairment (see section 4.3).
Reactions to excipients
This medicinal product contains sucrose and patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product.
This medicinal product contains parahydroxybenzoates and may cause allergic reactions (possibly delayed).
To ensure better efficacy in treatment of NSAID-related ulcers, stopping the causative agent should be strongly considered.
The maintenance treatment of ulcers associated with the intake of NSAIDs should be restricted to patients with a previous history of gastroduodenal lesions.
Duration of therapy
Because of limited safety data for patients on maintenance treatment for longer than 1 year, regular review of the treatment and thorough risk-benefit assessment should be performed in long-term use exceeding 1 year.
Potential interactions (monitoring of blood levels recommended)
During concomitant regimens with omeprazole and other medicinal products (for NSAID related ulcers or eradication therapy) caution should be exercised when administering additional medicinal products as interactions might occur (see section 4.5). This is particularly important with products with a narrow therapeutic index such as warfarin and phenytoin. Levels of these should be measured as a dose reduction may be needed. Levels of ciclosporin may be increased and therefore plasma levels should be monitored (see Section 4.5).
Monitoring vision and hearing
Although not known for orally administered omeprazole, blindness and deafness have been reported in the use of the injection form of omeprazole; therefore, in severely ill patients the monitoring of visual and auditory senses is recommended.
Hypomagnesaemia
Severe hypomagnesaemia has been reported in patients treated with PPIs like omeprazole for at least three months, and in most cases for a year. Serious manifestations of hypomagnesaemia such as fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmia can occur but they may begin insidiously and be overlooked. In most affected patients, hypomagnesaemia improved after magnesium replacement and discontinuation of the PPI.
For patients expected to be on prolonged treatment or who take PPIs with digoxin or drugs that may cause hypomagnesaemia (e.g., diuretics), health care professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment.
Risk of fracture
Proton pump inhibitors, especially if used in high doses and over long durations (>1 year), may modestly increase the risk of hip, wrist and spine fracture, predominantly in the elderly or in presence of other recognised risk factors. Observational studies suggest that proton pump inhibitors may increase the overall risk of fracture by 10-40%. Some of this increase may be due to other risk factors. Patients at risk of osteoporosis should receive care according to current clinical guidelines and they should have an adequate intake of vitamin D and calcium.
4.5 Interaction with other medicinal products and other forms of interaction
Cytochrome P450
Omeprazole is metabolised in the liver through cytochrome P450 isoforms (mainly CYP 2C19, S-mephenytoin hydroxylase) and inhibits enzymes of the CYP2C subfamily (CYP 2C19 and CYP 2C9) iFand can delay the elimination of other active substances metabolised by these enzymes. This has been observed for diazepam (and also of other benzodiazepines as triazolam or flurazepam), phenytoin and warfarin. Periodic monitoring of patients receiving warfarin or phenytoin is recommended and a reduction of warfarin or phenytoin dose may be necessary. Other active substances that could be affected are hexabarbital, citalopram, imipramine, and clomipramine. Omeprazole may inhibit the hepatic metabolism of disulfiram. Some possibly related cases of muscular rigidity have been reported.
Increased plasma concentrations
There are contradictionary data on the interaction of omeprazole with ciclosporin. Therefore, the plasma levels of ciclosporin should be monitored in those patients treated with omeprazole, because an increase in ciclosporin levels is possible.
Decreased absorption
Due to the decreased intragastric acidity, the absorption of ketoconazole or itraconazole may be reduced during omeprazole treatment.
Increased absorption
Simultaneous treatment with omeprazole and digoxin in healthy subjects lead to a 10 % increase in the bioavailability of digoxin as a consequence of the increased gastric pH.
Omeprazole may reduce the oral absorption of vitamin B12. This should be taken into account in those patients with low basal levels who undergo a longterm treatment with omeprazole.
Concomitant use contra-indicated (see Section 4.3)
Because of potential clinically significant decrease in omeprazole plasma concentrations, St. John’s wort should not be used concomitantly with omeprazole.
Due to the reduction in atazanavir sulphate exposure levels, atazanavir should not be co-administered with omeprazole.
Due to the increase of plasma concentrations of omeprazole and clarithromycin during concomitant administration, the combination therapy with clarithromycin should not be used in patients with hepatic impairment.
There is no evidence of an interaction of omeprazole with caffeine, propranolol, theophylline, metoprolol, lidocaine, quinidine, phenacetin, estradiol, amoxicillin, budesonide, diclofenac, metronidazole, naproxen, piroxicam, or antacids. The absorption of omeprazole is not affected by alcohol.
4.6 Pregnancy and lactation
Use of omeprazole during pregnancy and lactation requires a careful benefit-risk assessment.
Pregnancy
Limited epidemiologic studies indicate no adverse effects on pregnancy or increases in general malformation rate. However, but there is no information on individual abnormalities.
Lactation
In rats, omeprazole and its metabolites are excreted into milk. Omeprazole concentration in human breast milk reaches approximately 6% of the maximum plasma concentration in the mother but it is not known if this can affect the baby.
4.7 Effects on ability to drive and use machines
Sleepiness/drowsiness are common reactions associated with omeprazole and visual disturbances (see Section 4.8) have also been reported: if patients are affected they should not drive, operate machinery or take part in activities where these symptoms could put themselves or others at risk.
4.8. Undesirable effects
The following definitions apply to the incidence of the undesirable effects:
very common (>1/10)
common (>1/100, <1/10)
uncommon (>1/1,000, <1/100)
rare (>1/10,000, <1/1,000)
very rare (<1/10,000 including isolated reports)
Some of the common reactions such as sleepiness, insomnia, vertigo and headache, GI symptoms, improve during continued therapy.
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Blood and the lymphatic system disorders |
Rare: Hypochrome, microcytic anaemia in children. Very rare: thrombocytopenia, leucopenia, pancytopenia, agranulocytosis. |
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Immunosystem disorders |
Very rare: urticaria, fever, angioedema, bronchoconstriction, anaphylatic shock, allergic vasculitis, fever. |
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Nervous system disorders |
Common: somnolence, sleep disturbances (insomnia), vertigo, headaches and drowsiness. Rare: Paresthesia, light headedness. Mental confusion and hallucinations (predominantly in severely ill or elderly patients). Very rare: agitation and depression (predominantly in severely ill or elderly patients). |
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Eye disorders |
Uncommon: visual disturbances including blurred vision, loss of visual acuity and/or reduced field of vision. Blindness (see Section 4.4). |
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Ear and labyrinth disorders |
Uncommon: auditory dysfunction (e.g. tinnitus). Deafness (see Section 4.4) |
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Gastrointestinal disorders |
Common: diarrhoea, constipation, flatulence (possibly with abdominal pain), nausea, vomiting. Uncommon: taste disturbances. Rare: brownish-black discoloration of the tongue during concomitant administration of clarithromycin, benign fundic glandular cysts. Very rare: dryness of the mouth, stomatitis, candidiasis, |
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pancreatitis. | |
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Hepato-biliary disorders |
Uncommon: increase in liver enzyme values. Very rare: hepatitis with or without jaundice, hepatic failure and encephalopathy in patients with pre-existing severe liver disease. |
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Skin and subcutaneous tissue disorders: |
Uncommon: pruritus, skin eruptions, alopecia, erythema multiforme, photosensitivity and increased tendency to sweat. Very rare: Stevens-Johnson-syndrome or toxic epidermal necrolysis |
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Musculoskeletal, connective tissue and bone disorders |
Uncommon: Fracture of the hip, wrist or spine (see section 4.4). Rare: muscle weakness, myalgia and joint pain. |
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Metabolism and nutritional disorders |
Frequency not known: hypomagnesaemia (See Special warnings and precautions for use 4.4). |
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Renal and urinary disorders |
Very rare: interstitial nephritis |
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Other adverse effects: |
Uncommon: peripheral oedema Very rare: hyponatremia, gynaecomastia. |
4.9 Overdose
There have been rare reports of omeprazole overdoses up to 2,400 mg as a single oral dose. Symptoms including nausea, vomiting, dizziness, abdominal pain, diarrhoea, headache, apathy, depression and confusion have been reported. However, these were transient and without serious outcome and no specific treatment was needed.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Drugs for peptic ulcer and gastro-oesophageal reflux disease (GORD), proton pump inhibitors.
ATC-code: A02B C01
Omeprazole, a substituted benzimidazole, is a gastric proton pump inhibitor, directly and dose-dependently inhibiting the enzyme H+,K+-ATPase, so blocking the final step of acid production from gastric parietal cells. It inhibits both basal and stimulated acid secretion, irrespective of the type of stimulus, increasing the pH value and reducing the volume of the gastric acid secretion. It has low affinity for other membrane-bound receptors (such as the histamine H2, muscarine M1 or gastrinergic receptors).
Omeprazole is a pro-drug and, as a weak base, accumulates in the acid environment of the parietal cells and will only become effective as an inhibitor of the H+, K+-ATPase after being protonised and rearranged.
In an acid environment (pH of less than 4) the protonised omeprazole is converted to the active metabolite - omeprazole sulphonamide which covalentlybinds to the proton pump. The duration of the inhibition of acid secretion is therefore substantially longerthan the period in which omeprazole-base is present in plasma. The degree of acid secretion is directly correlated to the area under the plasma concentration-time curve (AUC) but not to the plasma concentration at any given time.
Most available clinical experience form controlled randomised clinical trials indicate that omeprazole 20 mg twice daily in combination with two antibiotics for 1 week achieve >80% Helicobacter pylori eradication rate in patients with gastro-duodenal ulcers. Significantly lower eradication rates were observed in patients with baseline antibiotic resistant Helicobacter pylori. Local information on the prevalence of resistance and local therapeutic guidelines should be taken into account in the choice of an appropriate combination regimen for Helicobacter pylori eradication therapy. Furthermore, in patients with persistent infection, potential development of secondary resistance (in patients with primary susceptible strains) to an antibacterial agent should be taken into account in the considerations for a new re-treatment regimen
5.2 Pharmacokinetic properties
Pharmacotherapeutic group: Drugs for peptic ulcer and gastro-oesophageal reflux disease (GORD), proton pump inhibitors.
ATC-code: A02B C01
Omeprazole, a substituted benzimidazole, is a gastric proton pump inhibitor, directly and dose-dependently inhibiting the enzyme H+,K+-ATPase, so blocking the final step of acid production from gastric parietal cells. It inhibits both basal and stimulated acid secretion, irrespective of the type of stimulus, increasing the pH value and reducing the volume of the gastric acid secretion. It has low affinity for other membrane-bound receptors (such as the histamine H2, muscarine M1 or gastrinergic receptors).
Omeprazole is a pro-drug and, as a weak base, accumulates in the acid environment of the parietal cells and will only become effective as an inhibitor of the H+, K+-ATPase after being protonised and rearranged.
In an acid environment (pH of less than 4) the protonised omeprazole is converted to the active metabolite - omeprazole sulphonamide which covalentlybinds to the proton pump. The duration of the inhibition of acid secretion is therefore substantially longerthan the period in which omeprazole-base is present in plasma. The degree of acid secretion is directly correlated to the area under the plasma concentration-time curve (AUC) but not to the plasma concentration at any given time.
Most available clinical experience form controlled randomised clinical trials indicate that omeprazole 20 mg twice daily in combination with two antibiotics for 1 week achieve >80% Helicobacter pylori eradication rate in patients with gastro-duodenal ulcers. Significantly lower eradication rates were observed in patients with baseline antibiotic resistant Helicobacter pylori. Local information on the prevalence of resistance and local therapeutic guidelines should be taken into account in the choice of an appropriate combination regimen for Helicobacter pylori eradication therapy. Furthermore, in patients with persistent infection, potential development of secondary resistance (in patients with primary susceptible strains) to an antibacterial agent should be taken into account in the considerations for a new re-treatment regimen.
5.3 Preclinical safety data
There are no findings from chronic toxicity investigations suggesting that any side effects known to date could occur in humans. Gastric ECL-cell hyperplasia and carcinoids have been observed in life-long studies in rats treated with omeprazole or subjected to partial fundectomy. These changes are the result of sustained hypergastrinaemia secondary to acid inhibition.
In mutagenicity studies (in-vitro and in-vivo) there were no findings of clinical relevance.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Capsule contents:
- Sugar spheres (containing sucrose and maize starch)
- Hypromellose
- Dimeticone emulsion (containing propyl-p-hydroxybenzoate, methyl-p-hydroxybenzoate, sorbic acid, sodium benzoate, polyethylene glycol sorbitan monolaureate, octylphenoxy polyethoxy ethanol and propylene glycol)
- Polysorbate 80
- Mannitol
- Diacetylated monoglycerides
- Talc
- Methacrylic acid - ethyl acrylate copolymer (1:1)
- Triethyl citrate
- Stearoyl macrogolglycerides
Capsules shell:
Omeprazole 10 mg Capsule:
Gelatin
Titanium dioxide (E171)
Yellow iron oxide (E172)
Black ink:
Shellac
Black iron oxide (E172)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years
6.4 Special precautions for storage
Do not store above 30° C. Store in the original package.
6.5 Nature and contents of container
PA-Aluminium-PVC/Aluminium foil blister, packed in cardboard boxes. Pack sizes: 7, 14, or 28 capsules.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirement.
7 MARKETING AUTHORISATION HOLDER
Waymade PLC t/a Sovereign Medical
Sovereign House
Miles Gray Road
Basildon
Essex
SS14 3FR
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
Omeprazole 10 mg Capsule: PL 06464/2396
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
16/07/2008
10 DATE OF REVISION OF THE TEXT
28/02/2013