1. Name of the medicinal product

Omeprazole Gastro-resistant Capsules 20mg BP Taj Pharma
Omeprazole Gastro-resistant Capsules 40mg BP Taj Pharma

2. Qualitative and quantitative composition

a) Each hard gelatin capsule contains :
Omeprazole B.P.? ? ? ? ? ? ? ? ? ? ? ? 20mg
(as enteric-coated granules)
Excipients? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? q.s
Approved colours used in empty capsule shells

b) Each hard gelatin capsule contains :
Omeprazole B.P.? ? ? ? ? ? ? ? ? ? ? ? 40mg
(as enteric-coated granules)
Excipients? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?q.s
Approved colours used in empty capsule shells

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Hard gelatin capsule.

4. Clinical particulars

4.1 Therapeutic indications

Omeprazole capsules are indicated for:

Adults

• Treatment of duodenal ulcers
• Prevention of relapse of duodenal ulcers
• Treatment of gastric ulcers
• Prevention of relapse of gastric ulcers
• In combination with appropriate antibiotics,?Helicobacter pylori (H. pylori)eradication in peptic ulcer disease
• Treatment of NSAID-associated gastric and duodenal ulcers
• Prevention of NSAID-associated gastric and duodenal ulcers in patients at risk
• Treatment of reflux oesophagitis
• Long-term management of patients with healed reflux oesophagitis
• Treatment of symptomatic gastro-oesophageal reflux disease
• Treatment of Zollinger-Ellison syndrome

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.

1. pylori eradication in peptic ulcer disease

For the eradication of?H. pylori?the selection of antibiotics should consider the individual patient’s drug tolerance, and should be undertaken in accordance with national, regional and local resistance patterns and treatment guidelines.

• Omeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1,000 mg, each twice daily for one week, or
• Omeprazole 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
• Omeprazole 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.

In each regimen, if the patient is still?H. pylori?positive, therapy may be repeated.

Treatment of NSAID-associated gastric and duodenal ulcers

For the treatment of NSAID–associated gastric and duodenal 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.

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

In patients with Zollinger-Ellison syndrome the dose should be individually adjusted and treatment continued as long as clinically indicated. The recommended initial dose is Omeprazole 60 mg daily. All patients with severe disease and inadequate response to other therapies have been effectively controlled and more than 90% of the patients maintained on doses of Omeprazole 20-120 mg daily. When dose exceed Omeprazole 80 mg daily, the dose should be divided and given twice daily.

Paediatric population

This formulation is not suitable for children.

Special populations

Renal impairment

Dose adjustment is not needed in patients with impaired renal function (see section 5.2).

Hepatic impairment

In patients with impaired hepatic function a daily dose of 10?20 mg may be sufficient (see section 5.2).

Elderly

Dose adjustment is not needed 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.

4.3 Contraindications

Hypersensitivity to the active substance, substituted benzimidazoles or to any of the excipients listed in section 6.1.

Omeprazole like other proton pump inhibitors (PPIs) must not be used concomitantly with 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 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 B₁₂?(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.

Hypomagnesaemia

Severe hypomagnesaemia has been reported in patients treated with proton pump inhibitors (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.

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.

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 capsules. SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors.

Interference with laboratory tests

Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, Omeprazole 10mg gastro-resistant capsules 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.

Omeprazole capsules contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal infections such as?Salmonella?and?Campylobacter?and, in hospitalised patients, possibly also?Clostridium difficile?(see section 5.1).

As in all long-term treatments, especially when exceeding a treatment period of 1 year, patients should be kept under regular surveillance.

4.5 Interaction with other medicinal products and other forms of interaction

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 nelfinavir 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.

Concomitant administration of omeprazole with atazanavir is not recommended (see section 4.4). Concomitant administration of omeprazole (40 mg once daily) and atazanavir 300 mg/ritonavir 100 mg to healthy volunteers resulted in a 75% decrease of the atazanavir exposure. Increasing the atazanavir dose to 400 mg 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.

Digoxin

Concomitant treatment with omeprazole (20 mg daily) and digoxin in healthy subjects increased the bioavailability of digoxin by 10%. 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.

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).

Other active substances

The absorption of posaconazole, erlotinib, ketoconazole and itraconazole is significantly reduced and thus clinical efficacy may be impaired. 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.

Cilostazol

Omeprazole, given in doses of 40 mg to healthy subjects in a cross-over study, increased C_max?and AUC for cilostazol by 18% and 26% respectively, and one of its active metabolites by 29% and 69% respectively.

Phenytoin

Monitoring phenytoin plasma concentration is recommended during the first two weeks after initiating omeprazole treatment and, if a phenytoin dose adjustment is made, monitoring and a further dose adjustment should occur upon ending omeprazole treatment.

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 has been reported to 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 of CYP2C19 and/or CYP3A4

Since omeprazole is metabolised by CYP2C19 and CYP3A4, active substances known to inhibit CYP2C19 or CYP3A4 (such as clarithromycin and voriconazole) may lead to increased omeprazole serum levels by decreasing omeprazole’s rate of metabolism. Concomitant voriconazole treatment resulted in more than doubling of the omeprazole exposure. As high doses of omeprazole have been well-tolerated adjustment of the omeprazole dose is not generally required. However, dose adjustment should be considered in patients with severe hepatic impairment and if long-term treatment is indicated.

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.

4.6 Fertility, pregnancy and lactation

Pregnancy

Results from three prospective epidemiological studies (more than 1000 exposed outcomes) indicate no adverse effects of omeprazole on pregnancy or on the health of the foetus/newborn child. Omeprazole can be used during pregnancy.

Breastfeeding

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

Omeprazole is not likely to affect the ability to drive or use machines. Adverse drug reactions such as dizziness and visual disturbances may occur (see section 4.8). If affected, patients should not drive or operate machinery.

4.8 Undesirable effects

Summary of the safety profile

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 to < 1/10), Uncommon (? 1/1,000 to < 1/100), Rare (? 1/10,000 to < 1/1,000), Very rare (< 1/10,000), Not known (cannot be estimated from the available data).

SOC/frequency	Adverse reaction
Blood and lymphatic system disorders
Rare:	Leukopenia, thrombocytopenia
Very rare:	Agranulocytosis, pancytopenia
Immune system disorders
Rare:	Hypersensitivity reactions e.g. fever, angioedema and anaphylactic reaction/shock
Metabolism and nutrition 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, somnolence
Rare:	Taste disturbance
Eye disorders
Rare:	Blurred vision
Ear and labyrinth disorders
Uncommon:	Vertigo
Respiratory, thoracic and mediastinal disorders
Rare:	Bronchospasm
Gastrointestinal disorders
Common:	Abdominal pain, constipation, diarrhoea, flatulence, nausea/vomiting, fundic gland polyps (benign)
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 subcutaneous tissue disorders
Uncommon:	Dermatitis, pruritus, rash, urticaria
Rare:	Alopecia, photosensitivity
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
Uncommon:	Fracture of the hip, wrist or spine (see section 4.4)
Rare:	Arthralgia, myalgia
Very rare:	Muscular weakness
Renal and urinary disorders
Rare:	Interstitial nephritis
Reproductive system and breast disorders
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.

4.9 Overdose

There is limited information available on the effects of overdoses of omeprazole in humans. 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 2,400 mg omeprazole (120 times the usual recommended clinical dose). Nausea, vomiting, dizziness, abdominal pain, diarrhoea and headache have been reported. Also apathy, depression and confusion have been described in single cases.

The symptoms described in connection to omeprazole overdose have been transient, and no serious outcome has been reported. The rate of elimination was unchanged (first order kinetics) with increased doses. Treatment, if needed, is symptomatic.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Drugs for acid-related disorder, proton pump inhibitors.

Mechanism of action

Omeprazole, a racemic mixture of two enantiomers reduces gastric acid secretion through a highly targeted mechanism of action. It is a specific inhibitor of the acid pump in the parietal cell. It is rapidly acting and provides control through reversible inhibition of gastric acid secretion with once daily dosing.

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 cell, where it inhibits the enzyme H⁺?K⁺-ATPase – the acid pump. This effect on the final step of the gastric acid formation process is dose-dependent and provides for highly effective inhibition of both basal acid secretion and stimulated acid secretion, irrespective of stimulus.

Pharmacodynamic effects

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

Effect on gastric acid secretion

Oral dosing with omeprazole once daily provides for rapid and effective inhibition of daytime and night-time gastric acid secretion with maximum effect being achieved within 4 days of treatment. With omeprazole 20 mg, a mean decrease of at least 80% in 24-hour intragastric acidity is then maintained in duodenal ulcer patients, with the mean decrease in peak acid output after pentagastrin stimulation being about 70% 24 hours after dosing.

Oral dosing with omeprazole 20 mg maintains an intragastric pH of ?3 for a mean time of 17 hours of the 24-hour period in duodenal ulcer patients.

As a consequence of reduced acid secretion and intragastric acidity, omeprazole dose-dependently reduces/normalizes acid exposure of the oesophagus in patients with gastro-oesophageal reflux disease.

The inhibition of acid secretion is related to the area under the plasma concentration-time curve (AUC) of omeprazole and not to the actual plasma concentration at a given time.

No tachyphylaxis has been observed during treatment with omeprazole.

Effect on H. pylori

1. pyloriis associated with peptic ulcer disease, including duodenal and gastric ulcer disease.?H. pyloriis a major factor in the development of gastritis.?H. pylori?together with gastric acid are major factors in the development of peptic ulcer disease.?H. pylori?is a major factor in the development of atrophic gastritis which is associated with an increased risk of developing gastric cancer.

Eradication of?H. pylori?with omeprazole and antimicrobials is associated with, high rates of healing and long-term remission of peptic ulcers.

Dual therapies have been tested and found to be less effective than triple therapies. They could, however, be considered in cases where known hypersensitivity precludes use of any triple combination.

Other effects related to acid inhibition

During long-term treatment gastric glandular cysts have been reported in a somewhat increased frequency. These changes are a physiological consequence of pronounced inhibition of acid secretion, are benign and appear to be reversible.

Decreased gastric acidity due to any means including proton pump inhibitors, increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with acid-reducing drugs may lead to slightly increased risk of gastrointestinal infections such as?Salmonella?and?Campylobacter?and, in hospitalised patients, possibly also?Clostridium difficile.

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 measurement. This is to allow CgA levels that might be spuriously elevated following PPI treatment to return to reference range.

An increased number of ECL cells possibly related to the increased serum gastrin levels, have been observed in some patients (both children and adults) during long term treatment with omeprazole. The findings are considered to be of no clinical significance.

Paediatric population

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 gastro-oesophageal reflux disease 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 H. pylori in children

A randomised, double blind clinical study (H?liot study) concluded that omeprazole in combination with two antibiotics (amoxicillin and clarithromycin), was safe and effective in the treatment of?H. pylori?infection in children age 4 years old and above with gastritis:?H. 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 any clinical benefit with respect to dyspeptic symptoms. This study does not support any information for children aged less than 4 years.

5.2 Pharmacokinetic properties

Absorption

Omeprazole and omeprazole magnesium are acid labile and are therefore administered orally as enteric-coated granules in capsules or enteric coated tablet. Absorption of omeprazole is rapid, with peak plasma levels occurring approximately 1-2 hours after dose. Absorption of omeprazole takes place in the small intestine and is usually completed within 3-6 hours. Concomitant intake of food has no influence on the bioavailability. The systemic availability (bioavailability) from a single oral dose of omeprazole is approximately 40%. After repeated once-daily administration, the bioavailability increases to about 60%.

Distribution

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

Biotransformation

Omeprazole is completely metabolised by the cytochrome P450 system (CYP). The major part of its metabolism is dependent on the polymorphically expressed CYP2C19, responsible for the formation of hydroxyomeprazole, the major metabolite in plasma. The remaining part is dependent on another specific isoform, CYP3A4, responsible for the formation of omeprazole sulphone. As a consequence of high affinity of omeprazole to CYP2C19, there is a potential for competitive inhibition and metabolic drug-drug interactions with other substrates for CYP2C19. However, due to low affinity to CYP3A4, omeprazole has no potential to inhibit the metabolism of other CYP3A4 substrates. In addition, omeprazole lacks an inhibitory effect on the main CYP enzymes.

Approximately 3% of the Caucasian population and 15-20% of Asian populations lack a functional CYP2C19 enzyme and are called poor metabolisers. In such individuals the metabolism of omeprazole is probably mainly catalysed by CYP3A4. After repeated once-daily administration of 20 mg omeprazole, the mean AUC was 5 to 10 times higher in poor metabolisers than in subjects having a functional CYP2C19 enzyme (extensive metabolisers). Mean peak plasma concentrations were also higher, by 3 to 5 times. These findings have no implications for the posology of omeprazole.

Elimination

The plasma elimination half-life of omeprazole is usually shorter than one hour both after single and repeated oral once-daily dosing. Omeprazole is completely eliminated from plasma between doses with no tendency for accumulation during once-daily administration. Almost 80% of an oral dose of omeprazole is excreted as metabolites in the urine, the remainder in the faeces, primarily originating from bile secretion.

Linearity/non-linearity

The AUC of omeprazole increases with repeated administration. This increase is dose-dependent and results in a non-linear dose-AUC relationship after repeated administration. This time- and dose-dependency is due to a decrease of first pass metabolism and systemic clearance probably caused by an inhibition of the CYP2C19 enzyme by omeprazole and/or its metabolites (e.g. the sulphone).

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

Special populations

Hepatic impairment

The metabolism of omeprazole in patients with liver dysfunction is impaired, resulting in an increased AUC. Omeprazole has not shown any tendency to accumulate with once daily dosing.

Renal impairment

The pharmacokinetics of omeprazole, including systemic bioavailability and elimination rate, are unchanged in patients with reduced renal function.

Elderly

The metabolism rate of omeprazole is somewhat reduced in elderly subjects (75-79 years of age).

Paediatric population

During treatment with the recommended doses to children from the age of 1 year, similar plasma concentrations were obtained as compared to adults. In children younger than 6 months, clearance of omeprazole is low due to low capacity to metabolise omeprazole.

5.3 Preclinical safety data

Gastric ECL-cell hyperplasia and carcinoids, have been observed in life-long studies in rats treated with omeprazole. These changes are the result of sustained hypergastrinaemia secondary to acid inhibition. Similar findings have been made after treatment with H₂-receptor antagonists, proton pump inhibitors and after partial fundectomy. Thus, these changes are not from a direct effect of any individual active substance.

6. Pharmaceutical particulars

6.1 List of excipients

Lactose monohydrate, sodium starch glycolate, sodium stearate, sodium stearyl fumarate, hypromellose acetate succinate, talc, triethyl citrate, monoethanolamine, sodium laurilsulfate, carnauba wax, gelatin, titanium dioxide, red iron oxide.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years

6.4 Special precautions for storage

Do not store above 30?C.

Blister: Store in the original package in order to protect from moisture.

6.5 Nature and contents of container

Aluminum blister.

Pack size: 7, 14, 28, 30, 50, 100 and 500 capsules.

Not all pack sizes may be marketed

6.6 Special precautions for disposal and other handling

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of ?Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail:?tajgroup@tajpharma.com

Omeprazole Gastro-resistant Capsules BP 20mg/40mg Taj Pharma
(Omeprazole)

Package leaflet: Information for the user

Read all of this leaflet carefully before you start taking this medicine.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. (See section 4).

What is in this leaflet

1. What Omeprazole Capsules are and what they are used for
   2. What you need to know before you take Omeprazole Capsules
   3. How to take Omeprazole Capsules
   4. Possible side effects
   5. How to store Omeprazole Capsules
   6. Contents of the pack and other information

 

1. What Omeprazole Capsules are and what they are used for

Omeprazole Capsules contains the active substance omeprazole. It belongs to a group of medicines called ?proton pump inhibitors?. They work by reducing the amount of acid that your stomach produces.

Omeprazole Capsules is used to treat the following conditions:

In adults:

• ?Gastro-oesophageal reflux disease? (GORD). This is where acid from the stomach escapes into the gullet (the tube which connects your throat to your stomach) causing pain, inflammation and heartburn.
• Ulcers in the upper part of the intestine (duodenal ulcer) or stomach (gastric ulcer).
• Ulcers which are infected with bacteria called ?Helicobacter pylori?. If you have this condition, your doctor may also prescribe antibiotics to treat the infection and allow the ulcer to heal.
• Ulcers caused by medicines called NSAIDs (Non-Steroidal Anti-Inflammatory Drugs). Omeprazole Capsules can also be used to stop ulcers from forming if you are taking NSAIDs.
• Too much acid in the stomach caused by a growth in the pancreas (Zollinger-Ellison syndrome).

2. What you need to know before you take Omeprazole Capsules

Do not take Omeprazole Capsules

• If you are allergic (hypersensitive) to omeprazole or any of the other ingredients of Omeprazole Capsules.
• If you are allergic to medicines containing other proton pump inhibitors (eg pantoprazole, lansoprazole, rabeprazole, esomeprazole).
• If you are taking a medicine containing nelfinavir (used for HIV infection)

Do not take Omeprazole Capsules if any of the above applies to you.?If you are not sure, talk to your doctor or pharmacist before taking Omeprazole Capsules.

Warnings and precautions

Tell your doctor before taking this medicine, if:

• You are due to have a specific blood test (Chromogranin A)

Omeprazole Capsules may hide the symptoms of other diseases. Therefore, if any of the following happen to you before you start taking Omeprazole Capsules or while you are taking it, talk to your doctor straight away:

• You lose a lot of weight for no reason and have problems swallowing.
• You get stomach pain or indigestion.
• You begin to vomit food or blood.
• You pass black stools (blood-stained faeces).
• You experience severe or persistent diarrhoea, as omeprazole has been associated with a small increase in infectious diarrhoea.
• You have severe liver problems.
• You have ever had a skin reaction after treatment with a medicine similar to Omeprazole Capsules that reduces stomach acid.

If you get a rash on your skin, especially in areas exposed to the sun tell your doctor as soon as you can, as you may need to stop your treatment with Omeprazole Capsules. Remember to also mention any other ill-effects like pain in your joints.

Omeprazole may reduce magnesium level in blood, especially if you are taking it for more than 3 months; Talk to your doctor if you are taking Digoxin or water tablets, as they may increase the risk of low magnesium level.

Taking a proton pump inhibitor like Omeprazole Capsules, especially over a period of more than one year, may slightly increase your risk of fracture in the hip, wrist or spine. Tell your doctor if you have osteoporosis or if you are taking corticosteroids (which can increase the risk of osteoporosis).

If you take Omeprazole Capsules on a long-term basis (longer than 1 year) your doctor will probably keep you under regular surveillance.?You should report any new and exceptional symptoms and circumstances whenever you see your doctor.

Other medicines and Omeprazole Capsules

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,?including medicines obtained without a prescription. This is because Omeprazole Capsules can affect the way some medicines work and some medicines can have an effect on Omeprazole Capsules.

Do not take Omeprazole Capsules if you are taking a medicine containing?nelfinavir?(used to treat HIV infection).

Tell your doctor or pharmacist if you are taking any of the following medicines:

• Ketoconazole, itraconazole, posaconazole or voriconazole (used to treat infections caused by a fungus)
• Digoxin (used to treat heart problems)
• Diazepam (used to treat anxiety, relax muscles or in epilepsy)
• Phenytoin (used in epilepsy). If you are taking phenytoin, your doctor will need to monitor you when you start or stop taking Omeprazole Capsules
• Medicines that are used to thin your blood, such as warfarin or other vitamin K blockers. Your doctor may need to monitor you when you start or stop taking Omeprazole Capsules
• Rifampicin (used to treat tuberculosis)
• Atazanavir (used to treat HIV infection)
• Tacrolimus or mycophenolate mofetil (in cases of organ transplantation)
• St John?s wort (Hypericum perforatum) (used to treat mild depression)
• Cilostazol (used to treat intermittent claudication)
• Saquinavir (used to treat HIV infection)
• Clopidogrel (used to prevent blood clots (thrombi))
• Erlotinib (used to treat cancer)
• Methotrexate (a chemotherapy medicine used in high doses to treat cancer) ? if you are taking a high dose of methotrexate, your doctor may temporarily stop your Omeprazole Capsules treatment

If your doctor has prescribed the antibiotics amoxicillin and clarithromycin as well as Omeprazole Capsules to treat ulcers caused by Helicobacter pylori infection, it is very important that you tell your doctor about any other medicines you are taking.

Taking Omeprazole Capsules with food and drink

You can take your Capsules with food or on an empty stomach.

Pregnancy, breast-feeding and fertility:

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Omeprazole is excreted in breast milk but is not likely to influence the child when therapeutic doses are used. Your doctor will decide whether you can take Omeprazole Capsules if you are breast-feeding.

Driving and using machines

Omeprazole Capsules is not likely to affect your ability to drive or use any tools or machines. Side effects such as dizziness and visual disturbances may occur (see section 4). If affected, you should not drive or operate machinery.

Important information about some of the ingredients of Omeprazole Capsules

Omeprazole Capsules contain lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

3. How to take Omeprazole Capsules

Always take Omeprazole Capsules exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Your doctor will tell you how many Capsules to take and how long to take them for. This will depend on your condition and how old you are.

The recommended doses are given below.

Adults:

To treat symptoms of GORD such as?heartburn and acid regurgitation:

• If your doctor has found that your food pipe (gullet) has been slightly damaged, the recommended dose is 20 mg once a day for 4-8 weeks. Your doctor may tell you to take a dose of 40 mg for a further 8 weeks if your gullet has not yet healed.
• The recommended dose once the gullet has healed is 10 mg once a day.
• If your gullet has not been damaged, the recommended dose is 10 mg once a day.

To treat?ulcers in the upper part of the intestine (duodenal ulcer):

• The recommended dose is 20 mg once a day for 2 weeks. Your doctor may tell you to take the same dose for a further 2 weeks if your ulcer has not yet healed.
• If the ulcer does not fully heal, the dose can be increased to 40 mg once a day for 4 weeks.

To treat?ulcers in the stomach?(gastric ulcer):

• The recommended dose is 20 mg once a day for 4 weeks. Your doctor may tell you to take the same dose for a further 4 weeks if your ulcer has not yet healed.
• If the ulcer does not fully heal, the dose can be increased to 40 mg once a day for 8 weeks.

To?prevent the duodenal and stomach ulcers?from coming back:

• The recommended dose is 10 mg or 20 mg once a day. Your doctor may increase the dose to 40 mg once a day.

To treat duodenal and stomach?ulcers caused by NSAIDs?(Non-Steroidal Anti-Inflammatory Drugs):

• The recommended dose is 20 mg once a day for 4?8 weeks.

To?prevent duodenal and stomach ulcers?if you are taking NSAIDs:

• The recommended dose is 20 mg once a day.

To treat?ulcers caused by Helicobacter pylori infection?and to stop them coming back:

• The recommended dose is 20 mg Omeprazole Capsules twice a day for one week.
• Your doctor will also tell you to take two antibiotics among amoxicillin, clarithromycin and metronidazole.

To treat too much acid in the stomach caused by a?growth in the pancreas (Zollinger-Ellison syndrome):

• The recommended dose is 60 mg daily.
• Your doctor will adjust the dose depending on your needs and will also decide how long you need to take the medicine for.

Children:

This formulation is not suitable for children.

Taking this medicine

• It is recommended that you take your Capsules in the morning.
• You can take your Capsules with food or on an empty stomach.
• Swallow your Capsules whole with half a glass of water. Do not chew or crush the Capsules. This is because the Capsules contain tablets coated with enteric coating which stops the medicine from being broken down by the acid in your stomach. It is important not to damage the Capsules.

If you take more Omeprazole Capsules than you should

If you take more Omeprazole Capsules than prescribed by your doctor,?talk to your doctor or pharmacist straight away.

If you forget to take Omeprazole Capsules

If you forget to take a dose, take it as soon as you remember it. However, if it is almost time for your next dose, skip the missed dose. Do not take a double dose to make up for a forgotten dose.

4. Possible side effects

Like all medicines, Omeprazole Capsules can cause side effects, although not everybody gets them.

If you notice any of the following rare but serious side effects, stop taking Omeprazole Capsules and contact a doctor immediately:

• Sudden wheezing, swelling of your lips, tongue and throat or body, rash, fainting or difficulties in swallowing (severe allergic reaction).
• Reddening of the skin with blisters or peeling. There may also be severe blisters and bleeding in the lips, eyes, mouth, nose and genitals. This could be ?Stevens-Johnson syndrome? or ?toxic epidermal necrolysis?.
• Yellow skin, dark urine and tiredness which can be symptoms of liver problems.

Other side effects include:

Common side effects?(may affect up to 1 in 10 people)

• Effects on your stomach or gut: diarrhoea, stomach pain, constipation, wind (flatulence).
• Feeling sick (nausea) or being sick (vomiting).
• Benign polyps in the stomach.

Uncommon side effects?(may affect up to 1 in 100 people)

• Swelling of the feet and ankles.
• Disturbed sleep (insomnia).
• Dizziness, tingling feelings such as ?pins and needles?, feeling sleepy.
• Spinning feeling (vertigo).
• Changes in blood tests that check how the liver is working.
• Skin rash, lumpy rash (hives) and itchy skin.
• Generally feeling unwell and lacking energy.
• Fractures of the hip, wrist or spine.

Rare side effects?(may affect up to 1 in 1,000 people)

• Blood problems such as a reduced number of white cells or platelets. This can cause weakness, bruising or make infections more likely.
• Allergic reactions, sometimes very severe, including swelling of the lips, tongue and throat, fever, wheezing.
• Low levels of sodium in the blood. This may cause weakness, being sick (vomiting) and cramps.
• Feeling agitated, confused or depressed.
• Taste changes.
• Eyesight problems such as blurred vision.
• Suddenly feeling wheezy or short of breath (bronchospasm).
• Dry mouth
• An inflammation of the inside of the mouth
• An infection called “thrush” which can affect the gut and is caused by a fungus.
• Liver problems, including jaundice which can cause yellow skin, dark urine, and tiredness.
• Hair loss (alopecia)
• Skin rash on exposure to sunshine
• Joint pains (arthralgia) or muscle pains (myalgia)
• Severe kidney problems (interstitial nephritis)
• Increased sweating

Very rare side effects?(may affect up to 1 in 10,000 people)

• Changes in blood count including agranulocytosis (lack of white blood cells).
• Seeing, feeling or hearing things that are not there (hallucinations).
• Severe liver problems leading to liver failure and inflammation of the brain.
• Sudden onset of a severe rash or blistering or peeling skin. This may be associated with a high fever and joint pains (Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis).
• Muscle weakness.
• Enlarged breasts in men.

Not Known?(frequency cannot be estimated from the available data)

• Inflammation in the gut (leading to diarrhoea).
• Hypomagnesaemia (low level of magnesium in the blood).
• Rash, possibly with pain in the joints.

If you are on Omeprazole Capsules for more than three months it is possible that the levels of magnesium in your blood may fall. Low levels of magnesium can be seen as fatigue, involuntary muscle contractions, disorientation, convulsions, dizziness, increased heart rate. If you get any of these symptoms, please tell your doctor promptly. Low levels of magnesium can also lead to a reduction in potassium or calcium levels in the blood. Your doctor may decide to perform regular blood tests to monitor your levels of magnesium.

Omeprazole Capsules may in very rare cases affect the white blood cells leading to immune deficiency.

If you have an infection with symptoms such as fever with a?severely?reduced general condition or fever with symptoms of a local infection such as pain in the neck, throat or mouth or difficulties in urinating, you must consult your doctor as soon as possible so that a lack of white blood cells (agranulocytosis) can be ruled out by a blood test. It is important for you to give information about your medicine at this time.

Do not be concerned by this list of possible side effects. You may not get any of them.?If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

5. How to store Omeprazole Capsules

• Keep out of the reach and sight of children.
• Do not use Omeprazole Capsules after the expiry date which is stated on the pack after EXP. The expiry date refers to the last day of that month.
• Do not store above 30?C.
• Store this blister in the original package or keep the bottle tightly closed in order to protect from moisture.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. Contents of the pack and other information

What Omeprazole Capsules contains

The active substance is omeprazole.

a) Each hard gelatin capsule contains :
Omeprazole B.P.? ? ? ? ? ? ? ? ? ? ? ? 20mg
(as enteric-coated granules)
Excipients? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? q.s
Approved colours used in empty capsule shells

b) Each hard gelatin capsule contains :
Omeprazole B.P.? ? ? ? ? ? ? ? ? ? ? ? 40mg
(as enteric-coated granules)
Excipients? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?q.s
Approved colours used in empty capsule shells

The other ingredients are: Lactose monohydrate, sodium starch glycolate, sodium stearate, sodium stearyl fumarate, hypromellose acetate succinate, talc, triethyl citrate, monoethanolamine, sodium laurilsulfate, carnauba wax, gelatin, titanium dioxide, red iron oxide.

What Omeprazole Capsules looks like and contents of the pack

Omeprazole gastro-resistant Capsules are hard gelatin Capsules.

Aluminium blister.

Pack size: 7, 14, 28, 30, 50, 100 and 500 capsules.

Not all pack sizes may be marketed

7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of ?Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail:?tajgroup@tajpharma.com