4. CLINICAL PARTICULARS

4.1 Therapeutic indications 
 

Omeprazole is indicated in adults and children over 1 year of age and ³ 10kg.

 

Omeprazole gastro-resistant capsules are indicated infor:

4.3 Contraindications

Hypersensitivity to the active substanceomeprazole, 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

Each 40mg Gastro-resistant capsule, hard contains Sunset Yellow (E110) and Allura red (E129). These may cause allergic reactions.

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).

4.6 Fertility, pregnancy and lactation

Breast-fFeeding

4.8 Undesirable effects

SOC/ Frequency	Adverse reaction
Blood and lymphatic system disorders
Rare:	Leukopenia, thrombocytopenia
Very rare:	Pancytopenia, agranulocytosis
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 and 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-Johnsons syndrome, toxic epidermal necrolysis (TEN)
Not known	Subacute cutaneous lupus erythematosus (see section 4.4)S
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.

 

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Other effects related to acid inhibition
During long-term treatment gastric glandular cysts have been reported in 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 hospitalized patients, possibly also Clostridium difficile.

10. DATE OF REVISION OF THE TEXT

March November 20176

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Omeprazole is indicated in adults and children over 1 year of age and 10kg.

Omeprazole gastro-resistant capsules are indicated infor:

4.3 Contraindications

Hypersensitivity to the active substanceomeprazole, 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).


Interference with laboratory tests

Each 40mg Gastro-resistant capsule, hard contains Sunset Yellow (E110) and Allura red (E129). These may cause allergic reactions.

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).

4.6 Fertility, pregnancy and lactation

Breast-fFeeding
Omeprazole is excreted in breast milk but is not likely to influence the child when therapeutic doses are used.

4.8 Undesirable effects

Gastrointestinal disorders
Common:	Abdominal pain, constipation, diarrhoea, flatulence, nausea and vomiting, fundic gland polyps (benign)

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Other effects related to acid inhibition
During long-term treatment gastric glandular cysts have been reported in 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 hospitalized patients, possibly also Clostridium difficile.

10. DATE OF REVISION OF THE TEXT

March November 20176

4.2 Posology and method of administration

Special Populations:
RPatients with renal impairment
Dose adjustment is not required in patients with impaired renal function (see section 5.2).

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

ElderlyOlder people (> 65 years)
Dose adjustment is not required in the elderly (see section 5.2).

4.4 Special warnings and precautions for use

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 other medicines that may cause hypomagnesaemia (e.g. diuretics), healthcare 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 fractures 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 healthcare 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.
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 healthcare 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.

Interference with laboratory tests
Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference the omeprazole treatment should be temporarily stopped for at least five 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.

4.8 Undesirable effects

SOC/ Frequency	Adverse reaction
Blood and lymphatic system disorders
Rare:	Leukopenia, thrombocytopenia
Very rare:	Pancytopenia, agranulocytosis
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 and vomiting
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-Johnsons 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.

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 directly via HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2. Tel: +353 1 6764971, Fax: +353 1 6762517. Website: www.hpra.ie, E-mail: medsafety@hpra.ie

5.1  Pharmacodynamic properties

Other effects related to acid inhibition
During long-term treatment gastric glandular cysts have been reported in 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.

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.

Literature reports indicateAvailable published evidence suggests that proton pump inhibitors treatment should be discontinued between stopped at least 5 days and 2 weeks prior to before CgA measurements. This is to allow CgA levels that might be spuriously elevated following PPI treatment to return to reference range. If CgA and gastrin levels have not normalised after 5 days, measurements should be repeated 14 days after cessation of omeprazole treatment.

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.


 

 

4.4 Special warnings and precautions for use

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 healthcare 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.

 

4.8 Undesirable effects

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 and vomiting
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-Johnsons 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.

SOC/ Frequency	Adverse reaction
Blood and lymphatic system disorders
Rare:	Leukopenia, thrombocytopenia
Very rare:	Pancytopenia, agranulocytosis
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

section 4.8 Undesirable effects

Metabolism and nutrition disorders
Rare:	Hyponatraemia
Not Known:	Hypomagnesaemia; severe hypomagnesaemia may result in hypocalcaemia Hypomagnesaemia may also be assoiated with hypokalaemia.

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 directly via HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2. Tel: +353 1 6764971, Fax: +353 1 6762517. Website: www.hpra.ie, e-mail: medsafety@hpra.ie

Section 2: Qualitative and quantitative  composition
'Each 20mg Gastro-resistant capsules, hard contains 0.0029mg Tartrazine(E102) and 0.0104mg ALlura red (E129)....removed text

Section 4.4: Special warnings and precautions for use
'Each 20mg Gastro-resistant capsule, hard contains Tartrazine (E102) and Allura red (E129).....removed text

Section 4.8: Undesirable effects-Reporting of suspected adverse reactions..updated

Section 6: Pharmaceutical Particulars
6.1. List of excipients
20mg
Shell cap
Titanium dioxide(E171), Iron oxide black, Iron Oxide red(E172), Tartrazine (E102), Brilliant blue(E133), Allura red(E129), Gelatin, Sodium lauryl sulphate.

Sections 4.2, 4.4, 4.5, 4.8, 5.1 and 10 updated with numerous changes.

section 4.4:text added

Interference with laboratory tests

Increased CgA level may interfere with investigations for neuroendocrine tumours. To avoid this interference the omeprazole treatment should be temporarily stopped five days before CgA measurements.

 

section 6.5: text updated to remove (hospital packaging)

Round wide mouth white coloured HDPE bottle with white opaque PP screw cap induction sealing line.

7, 14, 15, 21, 28, 30, 50, 56, 60, 84, 100, 112 200, 500 in bottles

2 x 50

250 (dose dispensing in hospitals – bottle only)

 

Aluminium/Polyamide/PVC blister.

7, 14, 15, 21, 28, 30, 50, 56, 60, 84, 98, 100, 112, 200, 500 in blisters

2 x 50

 

None provided