Omeprazole 20 Mg Capsules
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Omeprazole 20 mg Capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains omeprazole 20 mg.
For excipients, see section 6.1
3 PHARMACEUTICAL FORM
Capsule, hard containing gastro-resistant granules
Each capsule consists of an orange body and blue cap and contains white to beige granules marked with O20.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
1. Treatment of reflux oesophagitis disease. In reflux oesophagitis the majority of patients are healed after 4 weeks. Symptom relief is rapid.
2. Treatment of duodenal and benign gastric ulcers including complicating NSAID therapy.
3. Relief of reflux-like symptoms (e.g. heartburn) and/or ulcer-like symptoms (e.g. epigastric pain) associated with acid-related dyspepsia.
4. Treatment and prophylaxis of NSAID-associated benign gastric ulcers, duodenal ulcers and gastroduodenal erosions in patients with a previous history of gastroduodenal lesions who require continued NSAID treatment.
5. Relief of associated dyspeptic symptoms.
5. Helicobacter pylori eradication: When used with in combination with antibiotics, Omeprazole proves effective in the eradication of Helicobacter pylori (Hp) in peptic ulcer disease.
6. Prophylaxis of acid aspiration.
7. Zollinger-Ellison syndrome.
8. Children over 1 year of age and > 10 kg:
Reflux oesophagitis. Symptomatic treatment of heartburn and acid regurgitation in
gastroesophageal reflux disease.
4.2 Posology and method of administration
Posology
Adults
Treatment of duodenal ulcers
The recommended dose in patients with an active duodenal ulcer is Omeprazole 20 mg once daily. In most patients healing occurs within two weeks. For those patients who may not be fully healed after the initial course, healing usually occurs during a further two weeks treatment period. In patients with poorly responsive duodenal ulcer Omeprazole 40 mg once daily is recommended and healing is usually achieved within four weeks.
Prevention of relapse of duodenal ulcers
For the prevention of relapse of duodenal ulcer in H. pylori negative patients or when H. pylori eradication is not possible the recommended dose is Omeprazole 20 mg once daily. In some patients a daily dose of 10 mg may be sufficient. In case of therapy failure, the dose can be increased to 40 mg.
Treatment of gastric ulcers
The recommended dose is Omeprazole 20 mg once daily. In most patients healing occurs within four weeks. For those patients who may not be fully healed after the initial course, healing usually occurs during a further four weeks treatment period. In patients with poorly responsive gastric ulcer Omeprazole 40 mg once daily is recommended and healing is usually achieved within eight weeks.
Prevention of relapse of gastric ulcers
For the prevention of relapse in patients with poorly responsive gastric ulcer the recommended dose is Omeprazole 20 mg once daily. If needed the dose can be increased to Omeprazole 40 mg once daily.
Acid-related dyspepsia
Usual dosage is 10 mg or 20 mg omeprazole once daily for 2-4 weeks
depending on the severity and persistence of symptoms. Should the patient not respond to treatment after 4 weeks or who relapse shortly after treatment, should be investigated.
Prophylaxis of acid aspiration
For patients considered to be at risk of aspiration of the gastric contents during general anaesthesia, the recommended dosage is omeprazole 40 mg on the evening before surgery followed by a further 40 mg, 2 - 6 hours prior to surgery.
Helicobacter pylori (Hp) eradication regimens in peptic ulcer disease: Omeprazole is recommended at a dose of 40 mg once daily or 20 mg twice daily concomitant with antimicrobial agents as detailed below:
Triple therapy regimens in duodenal ulcer disease Omeprazole and the following antimicrobial combinations
• Amoxicillin1g and clarithromycin 500 mg both twice a day for one week
• Clarithromycin 250 mg and metronidazole 400 mg (or tinidazole 500 mg) both twice a day for one week
• Amoxicillin 500 mg and metronidazole 400 mg both three times a day for one week
Dual therapy regimens in duodenal ulcer disease
Omeprazole and amoxicillin 750 mg to 1g twice daily for two weeks.
Alternatively, omeprazole and clarithromycin 500 mg three times a day for two
weeks.
Dual therapy regimens in gastric ulcer disease
Omeprazole and amoxicillin 750 mg to 1g twice daily for two weeks.
In each regimen if symptoms return and the patient tests positive for Hp, therapy may be repeated or one of the alternative regimens can be used; if the patient is Hp negative then see dosage instructions for acid reflux disease. To ensure healing in patients with active peptic ulcer disease, see further dosage recommendations for duodenal and benign gastric ulcer.
Treatment of NSAID-associated gastric ulcers, duodenal ulcers or gastroduodenal erosions
The recommended dosage of omeprazole is 20 mg once daily. Symptom resolution is rapid and in most patients healing occurs within 4 weeks. For those patients who may not be fully healed after the initial course, healing usually occurs during a further 4 weeks treatment period.
Prevention of NSAID-associated gastric and duodenal ulcers in patients at risk For the prevention of NSAID-associated gastric ulcers or duodenal ulcers in patients at risk (age> 60, previous history of gastric and duodenal ulcers, previous history of upper GI bleeding) the recommended dose is omeprazole 20 mg once daily.
Treatment of reflux oesophagitis
The recommended dose is Omeprazole 20 mg once daily. In most patients healing
occurs within four weeks. For those patients who may not be fully healed after the initial course, healing usually occurs during a further four weeks treatment period. In patients with severe oesophagitis Omeprazole 40 mg once daily is recommended and healing is usually achieved 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 Omeprazole 10 mg once daily. If needed, the dose can be increased to Omeprazole 20-40 mg once daily.
Treatment of symptomatic gastro-oesophageal reflux disease
The recommended dose is Omeprazole 20 mg daily. Patients may respond adequately to 10 mg daily, and therefore individual dose adjustment should be considered.
If symptom control has not been achieved after four weeks treatment with Omeprazole 20 mg daily, further investigation is recommended.
Treatment of Zollinger-Ellison syndrome
The initial starting dose is 60 mg omeprazole once a day. The dosage should be adjusted individually and treatment continued as long as clinically indicated.
More than 90% of patients with severe disease and inadequate response to other therapies have been effectively controlled on doses of 20- 120 mg daily. With doses above 80mg daily, the dose should be divided and given twice daily.
Paediatric population
Children over 1 year of age and > 10 kg
Treatment of reflux oesophagitis
Symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease
The dosage recommendations are as follows:
|
Age |
Weight |
Dosage |
|
>1 year of age |
10-20 kg |
10 mg once daily. The dosage can be increased to 20 mg once daily if needed |
|
>2 years of age |
>20 kg |
20 mg once daily. The dosage can be increased to 40 mg once daily if needed |
Reflux oesophagitis: The treatment time is 4-8 weeks.
Symptomatic treatment of heartburn and acid regurgitation in gastro-oesophageal reflux disease: The treatment time is 2-4 weeks. If symptom control has not been achieved after 2-4 weeks the patient should be investigated further.
Children and adolescents over 4 years of age
Treatment of duodenal ulcer caused by Helicobacter pylori In combination with antibiotics in treatment of duodenal ulcer caused by Helicobacter pylori. When selecting appropriate combination therapy consideration should be given to official local guidance regarding bacterial resistance, duration of treatment (most commonly 7 days but sometimes up to 14 days), and appropriate use of antibacterial agents.
The treatment should be supervised by a specialist.
The dosage recommendations are as follows:_
|
Weight |
Posology |
|
15-30 kg |
Combination with two antibiotics: Omeprazole 10 mg, amoxicillin 25 mg/kg body weight and clarithromycin 7.5 mg/kg body weight are all administrated together two times daily for one week. |
|
31-40 kg |
Combination with two antibiotics: Omeprazole 20 mg, amoxicillin 750 mg and clarithromycin 7.5 mg/kg body weight are all administrated two times daily for one week. |
|
> 40 kg |
Combination with two antibiotics: Omeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg are all administrated two times daily for one week. |
Special populations
Renal impairment
Dose adjustment is not required in patients with impaired renal function.
Hepatic impairment
As bioavailability and half-life can increase in patients with impaired hepatic function, the dose requires adjustment with a maximum daily dose 20 mg.
Elderly: (> 65 years old)
Dose adjustment is not required in the elderly (see section 5.2)
Method of administration
It is recommended to take Omeprazole capsules in the morning, swallowed whole with half a glass of water. The capsules must not be chewed or crushed.
Patients with swallowing difficulties:
Patients can open the capsule and swallow the contents with half a glass of water or after mixing the content in a slightly acidic fluid e.g., fruit juice, applesauce , yoghurt or in non-carbonated water. Patients should be advised that the dispersion should be taken immediately (or within 30 minutes) and always be stirred just before drinking and rinsed down with half a glass of water.
Alternatively patients can suck the capsule and swallow the pellets with half a glass of
water. It is important that the enteric-coated pellets must not be crushed or chewed.
4.3 Contraindications
Hypersensitivity to omeprazole, substituted benzimidazoles or any of the excipients listed in section 6.1.
When gastric ulcer is suspected, the possibility of malignancy should be excluded before treatment with Omeprazole 20 mg Capsules is commenced, as treatment may alleviate symptoms and delay diagnosis.
Omeprazole like other proton pump inhibitors (PPIs) should not be used concomitantly with atazanavir or nelfinavir (see section 4.5).
4.4 Special warnings and precautions for use
In the presence of any alarm symptom (e.g. significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis or melena) and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment may alleviate symptoms and delay diagnosis.
Co-administration of atazanavir or nelfinavir with proton pump inhibitors is not recommended (see section 4.5). If the combination of atazanavir with a proton pump inhibitor is judged unavoidable, close clinical monitoring (e.g virus load) is recommended in combination with an increase in the dose of atazanavir to 400 mg with 100 mg of ritonavir; omeprazole 20 mg should not be exceeded.
Omeprazole, as all acid-blocking medicines, may reduce the absorption of vitamin Bi2 (cyanocobalamin) due to hypo- or achlorhydria. This should be considered in patients with reduced body stores or risk factors for reduced vitamin B12 absorption on long-term therapy.
Omeprazole is a CYP2C19 inhibitor. When starting or ending treatment with omeprazole, the potential for interactions with drugs metabolised through CYP2C19 should be considered. An interaction is observed between clopidogrel and omeprazole (see section 4.5). The clinical relevance of this interaction is uncertain. As a precaution, concomitant use of omeprazole and clopidogrel should be discouraged.
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.
Interference with laboratory tests
Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, omeprazole treatment should be stopped for at least 5 days before CgA measurements (see section 5.1). If CgA and gastrin levels have not returned to reference range after initial measurement, measurements should be repeated 14 days after cessation of proton pump inhibitor treatment.
Some children with chronic illnesses may require long-term treatment although it is not recommended.
As in all long-term treatments, especially when exceeding a treatment period of 1 year, patients should be kept under regular surveillance.
Decreased gastric acidity due to any means, including proton-pump inhibitors, increases gastric counts of bacteria normally present in the gastrointestinal tract. Therefore treatment with acid-reducing drugs may lead to a slightly increased risk of gastrointestinal infections, such as Salmonella and Campylobacter.
Subacute cutaneous lupus erythematosus (SCLE)
Proton pump inhibitors are associated with very infrequent cases of SCLE. If lesions occur, especially in sun-exposed areas of the skin, and if accompanied by arthralgia, the patient should seek medical help promptly and the health care professional should consider stopping omeprazole. SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors.
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.
Omeprazole contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Interaction with other medicinal products and other forms of interaction
4.5
Effects of omeprazole on the pharmacokinetics of other active substances
Active substances with pH dependent absorption:
The decreased intragastric acidity during treatment with omeprazole might increase or decrease the absorption of active substances with a gastric pH dependent absorption.
Nelfinavir, atazanavir:
The plasma levels of nelfinavir and atazanavir are decreased in case of co administration with omeprazole.
Concomitant administration of omeprazole with nelfinavir is contraindicated (see section 4.3). Co-administration of omeprazole (40 mg once daily) reduced mean nelvinavir exposure by ca. 40% and the mean exposure of the pharmacologically active metabolite M8 was reduced by ca. 75 -90%. The interaction may also involve CYP2C19 inhibition.
Co-administration of omeprazole (40mg once daily) with atazanavir 300 mg/ritonavir 100mg to healthy volunteers resulted in a substantial reduction in atazanavir exposure (approximately 75% decrease in AUC, Cmax, and Cmin). Increasing the atazanavir dose to 400mg did not compensate for the impact of omeprazole on atazanavir exposure. The co-administration of omeprazole (20 mg once daily) with atazanavir 400 mg/ritonavir 100 mg to healthy volunteers resulted in a decrease of approximately 30% in the atazanavir exposure as compared to atazanavir 300 mg/ritonavir 100 mg once daily.
PPIs including omeprazole should not be co-administered with atazanavir (see section 4.3).
Clopidogrel:
Results from studies in healthy subjects have shown a pharmacokinetic (PK)/pharmacodynamic (PD) interaction between clopidogrel (300 mg loading dose/75 mg daily maintenance dose) and omeprazole (80 mg p.o. daily) resulting in a decreased exposure to the active metabolite of clopidogrel by an average of 46% and a decreased maximum inhibition of (ADP induced) platelet aggregation by an average of 16%.
Inconsistent data on the clinical implications of a PK/PD interaction of omeprazole in terms of major cardiovascular events have been reported from both observational and clinical studies. As a precaution, concomitant use of omeprazole and clopidogrel should be discouraged (see section 4.4).
Digoxin:
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 intragastric pH. Digoxin toxicity has been rarely reported.
However caution should be exercised when omeprazole is given at high doses in elderly patients. Therapeutic drug monitoring of digoxin should be then be reinforced.
Other active substances:
Due to the increased intragastric acidity the absorption of posaconazole, erlotinib, ketoconazole and itraconazole may be reduced during omeprazole treatment as it is during treatment with other acid secretion inhibitors. For posaconazole and erlotinib concomitant use should be avoided.
Active substances metabolised by CYP2C19:
Omeprazole is a moderate inhibitor of CYP2C19, the major omeprazole metabolising enzyme. Thus, the metabolism of concomitant active substances also metabolised by CYP2C19, may be decreased and the systemic exposure to these substances increased. Examples of such drugs are R-warfarin and other vitamin K antagonists, cilostazol, diazepam and phenytoin. In patients receiving warfarin or other vitamin K antagonists, monitoring of INR is recommended and a reduction of the warfarin (or other vitamin K antagonist) dose may be necessary. Similarly, concomitant treatment with Omeprazole 20 mg daily did not change coagulation time in patients on continuous treatment with warfarin.
Phenytoin:
Monitoring of patients receiving phenytoin is recommended and a reduction of the phenytoin dose may be required. However, concomitant treatment with Omeprazole 20 mg once daily did not change the blood concentration of phenytoin in patients on continuous treatment with phenytoin. If a phenytoin dose adjustment is made, monitoring and a further dose adjustment should occur upon ending omeprazole treatment.
Cilostazol:
Omeprazole, given in doses of 40 mg to healthy subjects in a cross-over study, increased Cmax and AUC for cilostazol by 18% and 26% respectively, and one of its active metabolites by 29% and 69% respectively.
Unknown mechanism
Saquinavir:
Concomitant administration of omeprazole with saquinavir/ritonavir resulted in increased plasma levels up to approximately 70% for saquinavir associated with good tolerability in HIV-infected patients.
Tacrolimus:
Concomitant administration of omeprazole and tacrolimus may increase the serum levels of tacrolimus. A reinforced monitoring of tacrolimus concentrations as well as renal function (creatinine clearance) should be performed, and dosage of tacrolimus adjusted if needed.
Methotrexate:
When given together with proton-pump inhibitors, methotrexate levels have been reported to increase in some patients. In high-dose methotrexate administration a temporary withdrawal of omeprazole may need to be considered.
Effects of other active substances on the pharmacokinetics of omeprazole
Inhibitors CYP2C19 and/or CYP3A4
Concomitant administration of omeprazole and a CYP2C19 and CYP3A4 inhibitor, voriconazole, resulted in more than doubling of the omeprazole exposure. Omeprazole (40 mg once daily) increased voriconazole (a CYP2C19 substrate) Cmax and AUC by 15% and 41%, respectively. A dose adjustment of omeprazole is not regularly required in either of these situations. However, dose adjustment should be considered in patients with severe hepatic impairment and if long-term treatment is indicated.
Plasma concentrations of omeprazole and clarithromycin are increased during concomitant administration. This is considered to be a useful interaction during H. pylori eradication. There is no interaction with metronidazole or amoxicillin. These antimicrobials are used together with omeprazole for eradication of Helicobacter pylori
Inducers of CYP2C19 and/or CYP3A4
Active substances known to induce CYP2C19 or CYP3A4 or both (such as rifampicin and St John's wort) may lead to decreased omeprazole serum levels by increasing omeprazole's rate of metabolism.
Drugs with no evidence of an interaction
There is no evidence of an interaction with phenacetin, theophylline, caffeine, propranolol, metoprolol, cyclosporin, lidocaine, quinidine, estradiol,
amoxicillin or antacids. The absorption of Omeprazole 20 mg Capsules is not affected by alcohol or food.
There is no evidence of an interaction with piroxicam, diclofenac or naproxen. This is considered useful when patients are required to continue these treatments.
4.6 Fertility, pregnancy and lactation Pregnancy
The analysis of the results from three epidemiological studies (more than 1000 exposed outcomes) has revealed no evidence of adverse events of omeprazole
on pregnancy or on the health of the foetus/newborn child. Omeprazole can be used during pregnancy.
Breast-feeding
Omeprazole is excreted in breast milk but is not likely to influence the child when therapeutic doses are used.
Fertility
Animal studies with the racemic mixture omeprazole, given by oral administration do not indicate effects with respect to fertility.
4.7 Effects on ability to drive and use machines
No forseen effects.
4.8 Undesirable effects
Summary of the safety profile
Omeprazole 20 mg Capsules are well tolerated and adverse reactions have generally been mild and reversible. The most common side effects (1-10% of patients) are headache, abdominal pain, constipation, diarrhoea, flatulence and nausea/vomiting.
Tabulated list of adverse reactions
The following adverse drug reactions have been identified or suspected in the clinical trials programme for Omeprazole and post-marketing. None was found to be dose-related. Adverse reactions listed below are classified according to frequency and System Organ Class (SOC).
Frequency categories are defined according to the following convention::
Very common >1/10
Common > 1/100
Uncommon > 1/1000 and < 1/100
Rare < 1/1000
Very rare <1/10,000
not known cannot be estimated from the available data
|
System Organ Class |
Frequency |
adverse event |
|
Blood and lymphatic system disorders |
Rare |
Leucopenia, Thrombocytopenia |
|
Very rare: |
Agranulocytosis and Pancytopenia |
|
Immune system disorders |
Rare |
Hypersensitivity reactions e.g.Angioedema, Fever, and Anaphylactic shock. |
|
Metabolic and nutritional disorders |
Rare |
Hyponatraemia |
|
Not known |
Hypomagnesaemia; Severe hypomagnesaemia may result in hypocalcaemia. Hypomagnesaemia may also be associated with hypokalaemia. | |
|
Psychiatric disorders |
Uncommon |
Insomnia |
|
Rare |
Agitation, Confusion, Depression | |
|
Very rare |
Aggression, Hallucinations | |
|
Nervous system disorders |
Common |
Headache |
|
Uncommon |
Dizziness, Paraesthesia, Light Headedness, Feeling faint, Somnolence, Insomnia and Vertigo | |
|
Rare |
Reversible mental, Confusion, Agitation, Aggression, Depression, Hallucinations and predominately in severely ill patients, Taste disturbance | |
|
Eye disorders |
Rare |
Blurred vision |
|
Ear and labyrinth disorders |
Uncommon |
Vertigo |
|
Respiratory, thoracic and mediastinal disorders |
Rare |
Bronchospasm |
|
Gastrointestinal disorders |
Common |
Diarrhoea, Constipation, Abdominal pain, Nausea, Vomiting, Flatulence |
|
Rare |
Dry mouth, Stomatitis, Gastrointestinal candidiasis | |
|
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 |
Uncommon |
Rash, Dermatitis and/or Pruritus, Urticaria |
|
subcutaneous tissue disorders |
Rare |
Alopecia, Photosensitivity, Bullous eruption, |
|
Very rare |
Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN) | |
|
Not known |
Subacute cutaneous lupus erythematosus (see section 4.4). | |
|
Musculoskeletal and connective tissue disorders |
Common |
Fracture of the hip, wrist or spine (see section 4.4) |
|
Rare |
Arthritic and myalgic symptoms | |
|
Very rare |
Muscular weakness | |
|
Renal and urinary disorders |
Rare |
Interstitial nephritis |
|
Reproductive system and breast disorders |
Rare |
Impotence |
|
Very rare |
Gynaecomastia | |
|
General disorders and administration site conditions |
Uncommon |
Malaise, Peripheral oedema |
|
Rare |
Increased sweating |
Paediatric population
The safety of omeprazole has been assessed in a total of 310 children aged 0 to 16 years with acid-related disease. There are limited long term safety data from 46 children who received maintenance therapy of omeprazole during a clinical study for severe erosive oesophagitis for up to 749 days. The adverse event profile was generally the same as for adults in short- as well as in 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 suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme website at: www.mhra.gov.uk/yellowcard
4.9 Overdose
Rare reports have been received of overdosage with omeprazole. In the literature, doses of up to 560 mg have been described and occasional reports have been received when single oral doses have reached up to 2400 mg omeprazole (120 times the usual recommended clinical dose). Nausea, vomiting, dizziness, abdominal pain, diarrhoea and headache have been
reported from overdosage with omeprazole. Also apathy, depression and confusion have been described in single cases.
The symptoms described in connection to omeprazole overdosage have been transient, and no serious outcome due to omeprazole has been reported. The rate of elimination was unchanged (first order kinetics) with increased doses and no specific treatment has been needed.
5.1 Pharmacodynamic properties
A TC code: A02B CO I - Drugs for peptic ulcers and gastro-oesophageal reflux disease - Proton Pump inhibitors.
Omeprazole reduces gastric acid secretion through a unique mechanism of action. It is a specific inhibitor of the gastric proton pump in the parietal cell. It is rapidly acting and produces reversible control of gastric acid secretion with once daily dosing.
An oral dose of 20 mg once a day produces a rapid and effective inhibition of gastric acid secretion with maximum effect being achieved within 4 days of treatment. In duodenal ulcer patients, a mean decrease of approximately 80% in 24-hour intragastric acidity is then maintained, with the mean decrease in peak acid output after pentagastrin stimulation being about 70%, twenty-four hours after dosing with Omeprazole 20 mg Capsules.
Clinical data for omeprazole in the prophylaxis of NSAID induced gastroduodenal lesions are derived from clinical studies of up to 6 months duration.
During treatment with antisecretory medicinal products, serum gastrin increases in response to the decreased acid secretion. Also CgA increases due to decreased gastric acidity. The increased CgA level may interfere with investigations for neuroendocrine tumours.
Available published evidence suggests that proton pump inhibitors should be discontinued between 5 days and 2 weeks prior to CgA measurements. This is to allow CgA levels that might be spuriously elevated following PPI treatment to return to reference range.
Helicobacter pylori (Hp) is associated with acid peptic disease including duodenal ulcer (DU) and gastric ulcer (GU) in which about 95% and
80% of patients respectively are infected with this bacterium. Hp is implicated as a major contributing factor in the development of gastritis and ulcers in such patients. Recent evidence also suggests a causative link between Hp and gastric carcinoma.
Omeprazole has been shown to have a bactericidal effect on Hp in vitro.
Eradication of Hp with omeprazole and antimicrobials is associated with rapid symptom relief, high rates of healing of any mucosal lesions, and long-term
remission of peptic ulcer disease thus reducing complications such as gastrointestinal bleeding as well as the need for prolonged anti-secretory treatment.
In recent clinical data in patients with acute peptic ulcer omeprazole Hp eradication therapy improved patients' quality of life.
During long-term treatment an increased frequency of gastric glandular cysts have been reported. These changes are a physiological consequence of pronounced inhibition of acid secretion. The cysts are benign and appear to be reversible. No other treatment related mucosal changes have been observed in patients treated continuously with omeprazole for periods up to 5 years.
Paediatric data
In a non-controlled study in children (1 to 16 years of age) with severe reflux oesophagitis, omeprazole at doses of 0.7 to 1.4 mg/kg improved oesophagitis level in 90 % of the cases and significantly reduced reflux symptoms. In a single-blind study, children aged 0-24 months with clinically diagnosed GERD 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 irrespective of the dose.
Eradication of Helicobacter pylori in children:
A randomised, double blind clinical study (Heliot study) has concluded to the efficacy and an acceptable safety for omeprazole associated to two antibiotics (amoxicillin and clarithromycin) in the treatment of Helicobacter pylori infection in children of 4 years old and above with a gastritis: Helicobacter pylori eradication rate: 74.2% (23/31 patients) with omeprazole + amoxicillin + clarithromycin versus 9.4% (3/32 patients) with amoxicillin + clarithromycin. However, there was no evidence of clinical benefit demonstrated regarding dyspeptic symptoms. This study does not support any information for children aged less than 4 years old.
Site and mechanism of action
Omeprazole is a weak base and is concentrated and converted to the active form in the acid environment of the intracellular canaliculi within the parietal cell, where it inhibits the enzyme H+ K+-ATPase - the proton pump. This effect on the final step of the gastric acid formation process is dose-dependent and provides for effective inhibition of both basal acid secretion and stimulated acid secretion irrespective of the stimulus.
All pharmacodynamic effects observed are explained by the effect of omeprazole on acid secretion.
5.2 Pharmacokinetic properties
Absorption and distribution
Omeprazole is acid labile and is administered orally as enteric-coated granules in capsules. Absorption takes place in the small intestine and is usually completed within 3-6 hours. The systemic bioavailability of omeprazole from a single oral dose is approximately 35%. After repeated once-daily administration, the bioavailability increases to about 60%. Concomitant intake of food has no influence on the bioavailability. The plasma protein binding of omeprazole is about 95%.
Elimination and metabolism
The average half-life of the terminal phase of the plasma concentration-time curve is approximately 40 minutes. There is no change in half-life during treatment. The inhibition of acid secretion is related to the area under the plasma concentration-time curve (AUC) but not to the actual plasma concentration at a given time.
Omeprazole is entirely metabolised, mainly in the liver. Identified metabolites in plasma are the sulphone, the sulphide and hydroxy-omeprazole, these metabolites have no significant effect on acid secretion. About 80% of the metabolites are excreted in the urine and the rest in the faeces. The two main urinary metabolites are hydroxy-omeprazole and the corresponding carboxylic acid.
The systemic bioavailability of omeprazole is not significantly altered in patients with reduced renal function. The area under the plasma concentrationtime curve is increased in patients with impaired liver function, but no tendency to accumulation of omeprazole has been found.
Children
Available data from children (1 year and older) suggest that the pharmacokinetics within the recommended doses are similar to those reported in adults. At steady state, lower plasma levels of omeprazole were seen in some children.
5.3 Preclinical safety data
Animal toxicity:
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, and not from a direct effect of any individual drug.
PHARMACEUTICAL PARTICULARS
6
6.1 List of excipients
Sugar spheres Sodium starch glycolate Sodium lauryl sulfate Povidone Potassium oleate Oleic acid Hypromellose
Methacrylic acid - ethyl acrylate copolymer (1:1)
Triethyl citrate
Titanium dioxide
Talc
Capsule
Gelatin
Titanium dioxide (E 171)
Quinoline yellow (E104)
Indigo carmine (El32)
Erythrosine (E 127)
Printing ink Shellac
Polyvinylpyrrolidone Sodium hydroxide Titanium dioxide (E171)
Propylene glycol
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. Keep the bottle tightly closed.
6.5 Nature and contents of container
HDPE bottle and polypropylene cap with integral silica gel desiccant Each pack contains 28 capsules.
6.6 Special precautions for disposal
No special instructions.
7 MARKETING AUTHORISATION HOLDER
Special Concept Development (UK) Limited,
Unit 1-7 Colonial Way,
Watford, Hertfordshire,
WD24 4YR United Kingdom.
8 MARKETING AUTHORISATION NUMBER(S)
PL 36722/0025
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
16/05/2005
10 DATE OF REVISION OF THE TEXT
14/09/2016