It is recommended that you also refer to http://www.medicines.ie as the Summary of Product Characteristics may have been updated since this copy was printed.

Ergha Healthcare Ltd

Damastown, Mulhuddart, Dublin 15,
Telephone: +353 1 8204438
Fax: +353 1 8225413
Medical Information e-mail: info@helsinn.com
Customer Care direct line: +353 1 8204438

Summary of Product Characteristics last updated on medicines.ie: 02/03/2009

BySec 20mg capsules



1. NAME OF THE MEDICINAL PRODUCT

BySec 20 mg gastro-resistant hard capsules


2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each gastro-resistant capsule contains 20 mg of omeprazole

For excipients, see section 6.1.


3. PHARMACEUTICAL FORM

Gastro-resistant capsule, hard

Opaque white capsule, with imprint "20 mg"


4. CLINICAL PARTICULARS

4.1 Therapeutic indications

•Treatment and prevention of relapse of reflux oesophagitis

•Eradication of Helicobacter pylori in patients with associated peptic ulcers, in

combination with appropriate antibacterial regimens (see section 4.2 Posology

and Method of Administration)

•Treatment and prevention of recurrence of duodenal ulcers

•Treatment of benign gastric ulcers

•Treatment of NSAID related gastric and duodenal ulcers. Prevention of

relapse of NSAID related gastric and duodenal ulcers is restricted to patients

with a previous history of these conditions

•Zollinger-Ellison syndrome.


4.2 Posology and method of administration

Reflux Oesophagitis

Treatment of reflux oesophagitis: The usual dose is 20 mg once daily. The duration of

treatment is 4-8 weeks. In severe/recurrent cases, the dose of omeprazole can be

increased to 40 mg once daily.

Maintenance treatment of reflux oesophagitis to prevent relapse: The usual daily dose

is 10 to 20 mg depending on clinical response.

Children above 2 years and adolescents with severe reflux oesophagitis:

As clinical experience in children is limited, omeprazole should only be used in

children with severe reflux oesophagitis resistant to other therapeutic measures and

treatment should be initiated by a hospital based paediatrician.

Continuous pH measurement and genotyping (concerning CYP 2C19 status) may be

performed, if appropriate, to determine optimal therapeutic regimen.

The following dose (equivalent to about 1 mg/kg/day) should be used:

Weight 10 kg to 20 kg: 10 mg/day

Weight over 20 kg: 20 mg/day

Treatment duration is usually 4 to 8 weeks and should not exceed 12 weeks due to lack

of data on long-term use in this age group.

Eradication therapy:

Patients with peptic ulcers due to Helicobacter pylori infection receive eradication

therapy with appropriate combinations of antibiotics at adequate doses. Selection of a

regimen should be based on therapeutic guidelines and relevant patient details.

Omeprazole 20 mg plus 2 antibiotics twice daily for 1 week has been used eg -

omeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg all bd : omeprazole

20 mg, clarithromycin 250 mg, metronidazole 400-500 mg all bd (see Section 5.1). To

avoid the development of resistance the treatment duration should not be reduced.

Combination therapy including metronidazole should not be considered as first choice

because of the carcinogenic potential of metronidazole and, if used, treatment should

be restricted to less than 10 days.

In patients with active ulcers an extension of the therapy with omeprazole

monotherapy – see posology and treatment duration below.

Duodenal and gastric ulcers

Omeprazole monotherapy is only for use if eradication therapy is not indicated or has

been unsuccessful (ie ulcers still active after adequate eradication regimen).

Treatment of duodenal ulcers: The usual dose is 20 mg once daily. The duration of the

treatment is 2-4 weeks.

Prevention of recurrence of duodenal ulcers: 10mg once daily.

Treatment of benign gastric ulcers: The usual dose is 20 mg once daily. The duration

of the treatment is 4-8 weeks.

In severe/recurrent cases of duodenal and gastric ulcers the dose of omeprazole can be

increased to 40 mg once daily.

NSAID related gastric and duodenal ulcers

Treatment of NSAID related gastric and duodenal ulcers: The usual dose is 20 mg

daily. The treatment duration is 4 to 8 weeks.

Maintenance treatment of NSAID related gastric and duodenal ulcers to prevent

relapse in patients with a history of these conditions: The usual dose is 20 mg daily.

Zollinger-Ellison syndrome:

The dose should be adjusted individually and continued under specialist supervision as

long as clinically indicated. The recommended initial dosage is 60 mg once daily.

Doses above 80 mg daily should be divided and given twice daily. In patients with

Zollinger-Ellison syndrome the treatment is not subject to a time limit.

Elderly: Dose adjustment is not required in the elderly.

Children: Omeprazole should not be used in children under 2 years of age (see section

4.3).

Impaired renal function: Dose adjustment is not required in patients with impaired

renal function.

Impaired hepatic function: As bioavailability and half-life can increase in patients

with impaired hepatic function, the dose may require adjustment with a maximum

daily dose of 20 mg.

Method of administration:

The capsules should be swallowed whole with sufficient fluid. The capsules should

not be chewed or milled. In patients with swallowing difficulties, the capsules may be

opened and the contents swallowed alone or suspended in a small amount of fruit juice

or yoghurt after gentle mixing.


4.3 Contraindications

Omeprazole is contraindicated in patients with hypersensitivity to omeprazole or to

any of the excipients.

Children under 2 years of age.

Concomitant use with St. John's wort or atazanavir sulphate (See section 4.5).

Combination therapy with clarithromycin should not be used in patients with hepatic

impairment (See section 4.5).


4.4 Special warnings and precautions for use

Prior to initiating treatment

In patients with peptic ulcer disease Helicobacter pylori-status should be determined

if relevant. In Helicobacter pylori-positive patients, the elimination of the bacterium

by eradication therapy should be the primary aim, wherever possible.

If a gastric ulcer is suspected, the possibility of malignancy must be excluded before

omeprazole is started, as treatment may alleviate symptoms and delay diagnosis.

The diagnosis of reflux oesophagitis should be confirmed endoscopically.

To ensure better efficacy in treatment of NSAID-related ulcers, stopping the causative

agent should be strongly considered.

The maintenance treatment of ulcers associated with the intake of NSAIDs should be

restricted to patients with a previous history of gastroduodenal lesions.

Risk of GI infections

Decreased gastric acidity increases gastric counts of bacteria normally present in the

gastro-intestinal tract. Treatment with acid-reducing medicinal products leads to a

slightly increased risk of gastrointestinal infections, such as Salmonella and

Campylobacter.

Patients with impaired hepatic or renal function

In patients with severe impaired hepatic function, liver enzyme values should be

checked periodically during treatment with omeprazole.

During combination treatment caution should be exercised in patients with renal or

hepatic dysfunction (for dose restriction see 4.2 Posology and Method of

Administration). Use with clarithromycin is contra-indicated in patients with hepatic

impairment (see section 4.3).

Reactions to excipients

This product contains sucrose and patients with rare hereditary problems of fructose

intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency

should not take this product.

This product contains parahydroxybenzoates and may cause allergic reactions

(possibly delayed).

Duration of therapy

Because of limited safety data for patients on maintenance treatment for longer than 1

year, regular review of the treatment and thorough risk-benefit assessment should be

performed in long-term use exceeding 1 year.

Potential interactions (monitoring of blood levels recommended)

During concomitant regimens with omeprazole and other medicinal products (for

NSAID related ulcers or eradication therapy) caution should be exercised when

administering additional medicinal products as interactions might occur (See Section

4.5). This is particularly important with products with a narrow therapeutic index such

as warfarin and phenytion. Levels of these should be measured as a dose reduction

may be needed. Levels of ciclosporin may be increased and therefore plasma levels

should be monitored (see section 4.5.).

Monitoring vision and hearing

Although not known with oral omeprazole, blindness and deafness have been reported

with the injectable form; therefore, in severely ill patients, monitoring of visual and

auditory senses is recommended.


4.5 Interaction with other medicinal products and other forms of interaction

Concomitant use contra-indicated (See section 4.3)

Because of potential clinically significant decrease in omeprazole plasma

concentrations, St. John's wort should not be used concomitantly with omeprazole.

Due to the reduction in atazanavir sulphate exposure levels, atazanavir should not be

co-administered with omeprazole.

Due to the increase of plasma concentrations of omeprazole and clarithromycin during

concomitant administration, the combination therapy with clarithromycin should not

be used in patients with hepatic impairment.

Cytochrome P450

Omeprazole is metabolised in the liver through cytochrome P450 isoforms (mainly

CYP 2C19, S-mephenytoin hydroxylase) and inhibits enzymes of the CYP2C

subfamily (CYP 2C19 and CYP 2C9) and can delay the elimination of other active

substances metabolised by these enzymes. This has been observed for phenytoin and

warfarin and benzodiazepines such as diazepam, triazolam and flurazepam. Periodic

monitoring of patients receiving warfarin or phenytoin is recommended and a

reduction of warfarin or phenytoin dose may be necessary. Other active substances

that could be affected are hexabarbital, citalopram, imipramine, and clomipramine.

Omeprazole may inhibit the hepatic metabolism of disulfiram with some possibly

related cases of muscular rigidity reported.

Increased plasma concentrations

There are contradictionary data on the interaction of omeprazole with ciclosporin.

Therefore, the plasma levels of ciclosporin should be monitored in those patients

treated with omeprazole, as an increase in ciclosporin levels is possible.

Increased absorption

Simultaneous treatment with omeprazole and digoxin in healthy subjects led to a 10 %

increase in the bioavailability of digoxin as a result of increased gastric pH.

Decreased absorption

Due to the decreased intragastric acidity, the absorption of ketoconazole or

itraconazole may be reduced during omeprazole treatment.

Omeprazole may reduce the oral absorption of vitamin B12. This should be taken into

account in patients with low basal levels who undergo a long-term treatment with

omeprazole.

There is no evidence of an interaction of omeprazole with caffeine, propranolol,

theophylline, metoprolol, lidocaine, quinidine, phenacetin, estradiol, amoxicillin,

budesonide, diclofenac, metronidazole, naproxen, piroxicam, or antacids. The

absorption of omeprazole is not affected by alcohol.


4.6 Pregnancy and lactation

Use of omeprazole during pregnancy and lactation requires a careful benefit-risk

assessment.

Pregnancy

Limited epidemiologic studies indicate no adverse effects on pregnancy or increases in

general malformation rate, but there is no information on individual abnormalities.

Lactation

In rats, omeprazole and its metabolites are excreted into milk. Omeprazole

concentration in human breast milk reaches approximately 6% of the maximum

plasma concentration in the mother but it is not known if this can affect the baby.


4.7 Effects on ability to drive and use machines

Sleepiness/drowsiness are common reactions associated with omeprazole and visual

disturbances (see section 4.8) have also been reported: if patients are affected they

should not drive, operate machinery of take part in activities where these symptoms

could put themselves or others at risk.


4.8 Undesirable effects

The following definitions apply to the incidence of the undesirable effects:

- very common >1/10)

- common >1/100, <1/10)

- uncommon >1/1,000, <1/100)

- rare >1/10,000, <1/1,000)

- very rare (<1/10,000 including isolated reports)

Some of the common reactions such as sleepiness, insomnia, vertigo and headache, GI

symptoms, improve during continued therapy

Blood and the lymphatic

system disorders

Rare: Hypochromic, microcytic anaemia in

children.

Very rare:,thrombocytopenia, leucopenia,

pancytopenia, agranulocytosis.

Immunosystem disorders

Very rare: urticaria, fever, angioedema,

bronchoconstriction, anaphylactic shock, allergic

vasculitis, fever.

Nervous system disorders

Common: somnolence/drowsiness, insomnia,

vertigo, headaches.

Rare: paresthesia, light headedness. Mental

confusion and hallucinations (predominantly in

severely ill or elderly patients).

Very rare: agitation and depression

(predominantly in severely ill or elderly

patients).

Eye disorders

Uncommon: visual disturbances including

blurred vision, loss of visual acuity and/or

reduced field of vision.

Blindness (see section 4.4 – monitoring vision

and hearing).

Ear and labyrinth disorders

Uncommon: tinnitus.

Deafness (see section 4.4 – monitoring vision

and hearing).

Gastrointestinal disorders

Common: diarrhoea, constipation, flatulence

(possibly with abdominal pain), nausea,

vomiting.

Uncommon: taste disturbance.

Rare: brownish-black discoloration of the tongue

during concomitant administration of

clarithromycin, benign fundic glandular cysts.

Very rare: dry mouth, stomatitis, candidiasis,

pancreatitis.

Hepato-biliary disorders

Uncommon: increase in liver enzyme values.

Very rare: hepatitis with or without jaundice.

Hepatic failure and encephalopathy in patients

with pre-existing severe liver disease.

Skin and subcutaneous tissue

disorders

Uncommon: pruritus, skin eruptions, alopecia,

erythema multiforme, photosensitivity, and

increased sweating.

Very rare: Stevens-Johnson syndrome or toxic

epidermal necrolysis.

Musculoskeletal, connective

tissue and bone disorders

Rare: muscle weakness, myalgia and joint pain.

 

Renal and urinary disorders

Very rare: interstitial nephritis.

Other adverse effects

Uncommon: peripheral oedema.

Very rare: hyponatraemia, gynaecomastia.


4.9 Overdose

There have been rare reports of omeprazole overdoses up to 2,400 mg as a single oral

dose. Symptoms including nausea, vomiting, dizziness, abdominal pain, diarrhoea,

headache, apathy, depression and confusion have been reported. However, these were

transient and without serious outcome and no specific treatment was needed.


5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Drugs for peptic ulcer and gastro-oesophageal reflux

disease (GORD), proton pump inhibitors.

ATC-code: A02B C01

Omeprazole, a substituted benzimidazole, is a gastric proton pump inhibitor, directly

and dose-dependently inhibiting the enzyme H+,K+-ATPase, so blocking the final step

of acid production from gastric parietal cells. It inhibits both basal and stimulated acid

secretion, irrespective of the type of stimulus, increasing the pH-value and reducing

the volume of the gastric acid secretion. It has low affinity for other membrane-bound

receptors (such as the histamine H2, muscarine M1 or gastrinergic receptors).

Omeprazole is a pro-drug and, as a weak base, accumulates in the acid environment of

the parietal cells and will only become effective after being protonised and rearranged.

In an acid environment (pH of less than 4) the protonised omeprazole is converted to

the active metabolite - omeprazole sulphonamide which covalently binds to the proton

pump. The duration of the inhibition of acid secretion is therefore substantially longer

than the period in which omeprazole-base is present in plasma. The degree of

inhibition of acid secretion is directly correlated to the area under the plasma

concentration-time curve (AUC) but not to the plasma concentration at any given

time.

Most available clinical experience form controlled randomised clinical trials indicate

that omeprazole 20 mg twice daily in combination with two antibiotics for 1 week

achieve>80% Helicobacter pylori eradication rate in patients with gastro-duodenal

ulcers. Significantly lower eradication rates were noted in patients with baseline

antibiotic-resistant Helicobacter pylori. Local information on the prevalence of

resistance and local therapeutic guidelines should be taken into account in the choice

of an appropriate combination regimen for Helicobacter pylori eradication therapy.

Furthermore, in patients with persistent infection, potential development of secondary

resistance (in patients with primary susceptible strains) to an antibacterial agent

should be taken into account in the considerations for a new re-treatment regimen.


5.2 Pharmacokinetic properties

Absorption & Distribution

Omeprazole is acid labile and is administered orally as gastro-resistant granules in

hard-gelatin capsules. Absorption takes place in the small intestine with peak plasma

concentrations of omeprazole occuring within 1 to 3 hours after oral administration. The

distribution volume of omeprazole in the body is relatively small (0.3 l/kg of body

weight) and corresponds to that of the extracellular fluid and approximately 95% is

protein bound.

After intravenous administration of 40 mg omeprazole for 5 days, the absolute

measured bioavailability increased by about 50 %; this can be explained by decreased

hepatic clearance due to saturation of the CYP2C19 enzyme.

Concomitant administration with food

Concomitant administration of food delays omeprazole absorption with lower peak

concentrations but without affecting bioavailability.

Metabolism

Omeprazole is entirely metabolised, mainly in the liver by CYP 2C19. A small

percentage of the patients lack a functional CYP2C19 enzyme and have reduced

elimination rate of omeprazole. The sulphone, sulphide and hydroxy-omeprazole

metabolites are found in plasma but have no significant effect on acid secretion.

About 20% of administered dose is excreted in faeces and the remaining 80% is

excreted in urine as metabolites (mainly hydroxy-omeprazole and the corresponding

carboxylic acid).

Elimination

The plasma half-life is about 40 minutes, and the total plasma clearance is 0.3 to 0.6

l/min. In a small percentage of the patients (CYP 2 C19 poor metabolisers) a reduced

elimination rate of omeprazole has been observed. In these cases, the terminal

elimination half-life can be approximately 3 times as long as the normal value, and the

area under the plasma concentration-time curve (AUC) can increase by up to 10 fold.

Pharmacokinetics in the elderly

The bioavailability of omeprazole is slightly elevated in the elderly and the

elimination rate slightly diminished, but individual values are nearly equal to that of

young healthy subjects and there is no indication that elderly patients on therapeutic

doses of omeprazole are at increased risk of increased adverse effects.

Pharmacokinetics in renal impairment

In patients with renal impairment, the kinetics of omeprazole was very similar to that

in healthy subjects. But, as renal elimination is the most important excretory pathway

for metabolised omeprazole, the elimination rate is reduced corresponding to the

degree of renal function reduction. Once daily administration can minimise

accumulation.

Pharmacokinetics in hepatic impairment

In patients with chronic hepatic disease the clearance of omeprazole is reduced, and

the plasma half-life can increase up to approximately 3 hours. The bioavailability can

then be greater than 90%. 20 mg of omeprazole once daily for 4 weeks was tolerated

well, and no accumulation of omeprazole or its metabolites was observed.


5.3 Preclinical safety data

There are no findings from chronic toxicity investigations suggesting that any side

effects unknown to date could occur in humans. Gastric ECL-cell hyperplasia and

carcinoids have been observed in life-long studies in rats treated with omeprazole or

subjected to partial fundectomy. These changes are the result of sustained

hypergastrinaemia secondary to acid inhibition.

In mutagenicity studies (in-vitro and in-vivo) there were no findings of clinical

relevance.


6. PHARMACEUTICAL PARTICULARS

6.1 List of excipient(s)

-Capsule contents:

- Sugar spheres (containing sucrose and maize starch)

- Hypromellose

- Dimeticone emulsion (containing propyl-p-hydroxybenzoate (E216), methyl-phydroxybenzoate (E218), sorbic acid, sodium benzoate, polyethylene glycol sorbitan

monolaureate, octylphenoxy polyethoxy ethanol and propylene glycol)

- Polysorbate 80

- Mannitol

- Diacetylated monoglycerides

- Talc

- Methacrylic acid – ethyl acrylate copolymer (1:1)

- Triethyl citrate

- Stearoyl macrogolglycerides

Capsules shell:

Gelatin

Titanium dioxide (E171)

Black ink :

Shellac

Black iron oxide (E172)


6.2 Incompatibilities

Not applicable.


6.3 Shelf life

HDPE bottles:

2 years

After first opening: 3 months

Aluminium blisters:

2 years


6.4 Special precautions for storage

HDPE bottles:

Do not store above 30°C. Store in the original package and keep the bottle tightly

closed.

Aluminium blisters:

Do not store above 30° C. Store in the original package.


6.5 Nature and contents of container

Bottles (HDPE) containing 1 g silica gel dessicant, sealed with an aluminium sheet,

with child resistant closure, packed in cardboard boxes.

Pack sizes: 7, 14, or 28 capsules.

PA-Aluminium-PVC/Aluminium foil blister, packed in cardboard boxes.

Peel-to-open, perforated unit dose blister:

- PA-Aluminium-PVC/Aluminium foil blister, packed in cardboard boxes

- PA-Aluminium-PVC/Aluminium-PET foil blister, packed in cardboard boxes

Pack sizes: 7, 14, 28, 30, 50, 60, 90 or 100 capsules.

Not all pack sizes may be marketed.


6.6 Special precautions for disposal and other handling

No special requirement.


7. MARKETING AUTHORISATION HOLDER

Ergha Healthcare Ltd.,

Damastown

Mulhuddart

Dublin 15


8. MARKETING AUTHORISATION NUMBER(S)

966/15/2

9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE

AUTHORISATION

13th May 2005/5th October 2005


10. DATE OF REVISION OF THE TEXT

February 2009



It is recommended that you also refer to http://www.medicines.ie as the Summary of Product Characteristics may have been updated since this copy was printed.