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.
Summary of Product Characteristics
last updated on medicines.ie:
|BySec 20 mg gastro-resistant hard capsules|
|Each gastro-resistant capsule contains 20 mg of omeprazoleFor excipients, see section 6.1.|
|Gastro-resistant capsule, hardOpaque white capsule, with imprint "20 mg"|
|Treatment and prevention of relapse of reflux oesophagitisEradication of Helicobacter pylori in patients with associated peptic ulcers, incombination with appropriate antibacterial regimens (see section 4.2 Posologyand Method of Administration)Treatment and prevention of recurrence of duodenal ulcersTreatment of benign gastric ulcersTreatment of NSAID related gastric and duodenal ulcers. Prevention ofrelapse of NSAID related gastric and duodenal ulcers is restricted to patientswith a previous history of these conditionsZollinger-Ellison syndrome.|
Reflux OesophagitisTreatment of reflux oesophagitis: The usual dose is 20 mg once daily. The duration oftreatment is 4-8 weeks. In severe/recurrent cases, the dose of omeprazole can beincreased to 40 mg once daily.Maintenance treatment of reflux oesophagitis to prevent relapse: The usual daily doseis 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 inchildren with severe reflux oesophagitis resistant to other therapeutic measures andtreatment should be initiated by a hospital based paediatrician.Continuous pH measurement and genotyping (concerning CYP 2C19 status) may beperformed, 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/dayWeight over 20 kg: 20 mg/dayTreatment duration is usually 4 to 8 weeks and should not exceed 12 weeks due to lackof data on long-term use in this age group.
Eradication therapy:Patients with peptic ulcers due to Helicobacter pylori infection receive eradicationtherapy with appropriate combinations of antibiotics at adequate doses. Selection of aregimen 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 : omeprazole20 mg, clarithromycin 250 mg, metronidazole 400-500 mg all bd (see Section 5.1). Toavoid the development of resistance the treatment duration should not be reduced.Combination therapy including metronidazole should not be considered as first choicebecause of the carcinogenic potential of metronidazole and, if used, treatment shouldbe restricted to less than 10 days.In patients with active ulcers an extension of the therapy with omeprazolemonotherapy see posology and treatment duration below.
Duodenal and gastric ulcersOmeprazole monotherapy is only for use if eradication therapy is not indicated or hasbeen unsuccessful (ie ulcers still active after adequate eradication regimen).Treatment of duodenal ulcers: The usual dose is 20 mg once daily. The duration of thetreatment 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 durationof the treatment is 4-8 weeks.In severe/recurrent cases of duodenal and gastric ulcers the dose of omeprazole can beincreased to 40 mg once daily.
NSAID related gastric and duodenal ulcersTreatment of NSAID related gastric and duodenal ulcers: The usual dose is 20 mgdaily. The treatment duration is 4 to 8 weeks.Maintenance treatment of NSAID related gastric and duodenal ulcers to preventrelapse 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 aslong 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 withZollinger-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 section4.3).Impaired renal function: Dose adjustment is not required in patients with impairedrenal function.Impaired hepatic function: As bioavailability and half-life can increase in patientswith impaired hepatic function, the dose may require adjustment with a maximumdaily dose of 20 mg.
Method of administration:The capsules should be swallowed whole with sufficient fluid. The capsules shouldnot be chewed or milled. In patients with swallowing difficulties, the capsules may beopened and the contents swallowed alone or suspended in a small amount of fruit juiceor yoghurt after gentle mixing.
|Omeprazole is contraindicated in patients with hypersensitivity to omeprazole or toany 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 hepaticimpairment (See section 4.5).|
Prior to initiating treatmentIn patients with peptic ulcer disease Helicobacter pylori-status should be determinedif relevant. In Helicobacter pylori-positive patients, the elimination of the bacteriumby eradication therapy should be the primary aim, wherever possible.If a gastric ulcer is suspected, the possibility of malignancy must be excluded beforeomeprazole 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 causativeagent should be strongly considered.The maintenance treatment of ulcers associated with the intake of NSAIDs should berestricted to patients with a previous history of gastroduodenal lesions.
Risk of GI infectionsDecreased gastric acidity increases gastric counts of bacteria normally present in thegastro-intestinal tract. Treatment with acid-reducing medicinal products leads to aslightly increased risk of gastrointestinal infections, such as Salmonella andCampylobacter.
Patients with impaired hepatic or renal functionIn patients with severe impaired hepatic function, liver enzyme values should bechecked periodically during treatment with omeprazole.During combination treatment caution should be exercised in patients with renal orhepatic dysfunction (for dose restriction see 4.2 Posology and Method ofAdministration). Use with clarithromycin is contra-indicated in patients with hepaticimpairment (see section 4.3).
Reactions to excipientsThis product contains sucrose and patients with rare hereditary problems of fructoseintolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiencyshould not take this product.This product contains parahydroxybenzoates and may cause allergic reactions(possibly delayed).
Duration of therapyBecause of limited safety data for patients on maintenance treatment for longer than 1year, regular review of the treatment and thorough risk-benefit assessment should beperformed in long-term use exceeding 1 year.
Potential interactions (monitoring of blood levels recommended)During concomitant regimens with omeprazole and other medicinal products (forNSAID related ulcers or eradication therapy) caution should be exercised whenadministering additional medicinal products as interactions might occur (See Section4.5). This is particularly important with products with a narrow therapeutic index suchas warfarin and phenytion. Levels of these should be measured as a dose reductionmay be needed. Levels of ciclosporin may be increased and therefore plasma levelsshould be monitored (see section 4.5.).
Monitoring vision and hearingAlthough not known with oral omeprazole, blindness and deafness have been reportedwith the injectable form; therefore, in severely ill patients, monitoring of visual andauditory senses is recommended.
Concomitant use contra-indicated (See section 4.3)Because of potential clinically significant decrease in omeprazole plasmaconcentrations, St. John's wort should not be used concomitantly with omeprazole.Due to the reduction in atazanavir sulphate exposure levels, atazanavir should not beco-administered with omeprazole.Due to the increase of plasma concentrations of omeprazole and clarithromycin duringconcomitant administration, the combination therapy with clarithromycin should notbe used in patients with hepatic impairment.Cytochrome P450Omeprazole is metabolised in the liver through cytochrome P450 isoforms (mainlyCYP 2C19, S-mephenytoin hydroxylase) and inhibits enzymes of the CYP2Csubfamily (CYP 2C19 and CYP 2C9) and can delay the elimination of other activesubstances metabolised by these enzymes. This has been observed for phenytoin andwarfarin and benzodiazepines such as diazepam, triazolam and flurazepam. Periodicmonitoring of patients receiving warfarin or phenytoin is recommended and areduction of warfarin or phenytoin dose may be necessary. Other active substancesthat could be affected are hexabarbital, citalopram, imipramine, and clomipramine.Omeprazole may inhibit the hepatic metabolism of disulfiram with some possiblyrelated cases of muscular rigidity reported.
Increased plasma concentrationsThere are contradictionary data on the interaction of omeprazole with ciclosporin.Therefore, the plasma levels of ciclosporin should be monitored in those patientstreated with omeprazole, as an increase in ciclosporin levels is possible.
Increased absorptionSimultaneous 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 absorptionDue to the decreased intragastric acidity, the absorption of ketoconazole oritraconazole may be reduced during omeprazole treatment.Omeprazole may reduce the oral absorption of vitamin B12. This should be taken intoaccount in patients with low basal levels who undergo a long-term treatment withomeprazole.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. Theabsorption of omeprazole is not affected by alcohol.
|Use of omeprazole during pregnancy and lactation requires a careful benefit-riskassessment.|
PregnancyLimited epidemiologic studies indicate no adverse effects on pregnancy or increases ingeneral malformation rate, but there is no information on individual abnormalities.
LactationIn rats, omeprazole and its metabolites are excreted into milk. Omeprazoleconcentration in human breast milk reaches approximately 6% of the maximumplasma concentration in the mother but it is not known if this can affect the baby.
|Sleepiness/drowsiness are common reactions associated with omeprazole and visualdisturbances (see section 4.8) have also been reported: if patients are affected theyshould not drive, operate machinery of take part in activities where these symptomscould put themselves or others at risk.|
|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, GIsymptoms, improve during continued therapy|
Blood and the lymphatic
Rare: Hypochromic, microcytic anaemia in
Very rare:,thrombocytopenia, leucopenia,
Very rare: urticaria, fever, angioedema,
bronchoconstriction, anaphylactic shock, allergic
Nervous system disorders
Common: somnolence/drowsiness, insomnia,
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
Uncommon: visual disturbances including
blurred vision, loss of visual acuity and/or
reduced field of vision.
Blindness (see section 4.4 monitoring vision
Ear and labyrinth disorders
Deafness (see section 4.4 monitoring vision
Common: diarrhoea, constipation, flatulence
(possibly with abdominal pain), nausea,
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,
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
Uncommon: pruritus, skin eruptions, alopecia,
erythema multiforme, photosensitivity, and
Very rare: Stevens-Johnson syndrome or toxic
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.
|There have been rare reports of omeprazole overdoses up to 2,400 mg as a single oraldose. Symptoms including nausea, vomiting, dizziness, abdominal pain, diarrhoea,headache, apathy, depression and confusion have been reported. However, these weretransient and without serious outcome and no specific treatment was needed.|
|Pharmacotherapeutic group: Drugs for peptic ulcer and gastro-oesophageal refluxdisease (GORD), proton pump inhibitors.ATC-code: A02B C01Omeprazole, a substituted benzimidazole, is a gastric proton pump inhibitor, directlyand dose-dependently inhibiting the enzyme H+,K+-ATPase, so blocking the final stepof acid production from gastric parietal cells. It inhibits both basal and stimulated acidsecretion, irrespective of the type of stimulus, increasing the pH-value and reducingthe volume of the gastric acid secretion. It has low affinity for other membrane-boundreceptors (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 ofthe 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 tothe active metabolite - omeprazole sulphonamide which covalently binds to the protonpump. The duration of the inhibition of acid secretion is therefore substantially longerthan the period in which omeprazole-base is present in plasma. The degree ofinhibition of acid secretion is directly correlated to the area under the plasmaconcentration-time curve (AUC) but not to the plasma concentration at any giventime.Most available clinical experience form controlled randomised clinical trials indicatethat omeprazole 20 mg twice daily in combination with two antibiotics for 1 weekachieve>80% Helicobacter pylori eradication rate in patients with gastro-duodenalulcers. Significantly lower eradication rates were noted in patients with baselineantibiotic-resistant Helicobacter pylori. Local information on the prevalence ofresistance and local therapeutic guidelines should be taken into account in the choiceof an appropriate combination regimen for Helicobacter pylori eradication therapy.Furthermore, in patients with persistent infection, potential development of secondaryresistance (in patients with primary susceptible strains) to an antibacterial agentshould be taken into account in the considerations for a new re-treatment regimen.|
Absorption & DistributionOmeprazole is acid labile and is administered orally as gastro-resistant granules inhard-gelatin capsules. Absorption takes place in the small intestine with peak plasmaconcentrations of omeprazole occuring within 1 to 3 hours after oral administration. Thedistribution volume of omeprazole in the body is relatively small (0.3 l/kg of bodyweight) and corresponds to that of the extracellular fluid and approximately 95% isprotein bound.After intravenous administration of 40 mg omeprazole for 5 days, the absolutemeasured bioavailability increased by about 50 %; this can be explained by decreasedhepatic clearance due to saturation of the CYP2C19 enzyme.
Concomitant administration with foodConcomitant administration of food delays omeprazole absorption with lower peakconcentrations but without affecting bioavailability.
MetabolismOmeprazole is entirely metabolised, mainly in the liver by CYP 2C19. A smallpercentage of the patients lack a functional CYP2C19 enzyme and have reducedelimination rate of omeprazole. The sulphone, sulphide and hydroxy-omeprazolemetabolites 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% isexcreted in urine as metabolites (mainly hydroxy-omeprazole and the correspondingcarboxylic acid).
EliminationThe plasma half-life is about 40 minutes, and the total plasma clearance is 0.3 to 0.6l/min. In a small percentage of the patients (CYP 2 C19 poor metabolisers) a reducedelimination rate of omeprazole has been observed. In these cases, the terminalelimination half-life can be approximately 3 times as long as the normal value, and thearea under the plasma concentration-time curve (AUC) can increase by up to 10 fold.
Pharmacokinetics in the elderlyThe bioavailability of omeprazole is slightly elevated in the elderly and theelimination rate slightly diminished, but individual values are nearly equal to that ofyoung healthy subjects and there is no indication that elderly patients on therapeuticdoses of omeprazole are at increased risk of increased adverse effects.
Pharmacokinetics in renal impairmentIn patients with renal impairment, the kinetics of omeprazole was very similar to thatin healthy subjects. But, as renal elimination is the most important excretory pathwayfor metabolised omeprazole, the elimination rate is reduced corresponding to thedegree of renal function reduction. Once daily administration can minimiseaccumulation.
Pharmacokinetics in hepatic impairmentIn patients with chronic hepatic disease the clearance of omeprazole is reduced, andthe plasma half-life can increase up to approximately 3 hours. The bioavailability canthen be greater than 90%. 20 mg of omeprazole once daily for 4 weeks was toleratedwell, and no accumulation of omeprazole or its metabolites was observed.
|There are no findings from chronic toxicity investigations suggesting that any sideeffects unknown to date could occur in humans. Gastric ECL-cell hyperplasia andcarcinoids have been observed in life-long studies in rats treated with omeprazole orsubjected to partial fundectomy. These changes are the result of sustainedhypergastrinaemia secondary to acid inhibition.In mutagenicity studies (in-vitro and in-vivo) there were no findings of clinicalrelevance.|
-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 sorbitanmonolaureate, 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:GelatinTitanium dioxide (E171)
Black ink :ShellacBlack iron oxide (E172)
HDPE bottles:2 yearsAfter first opening: 3 monthsAluminium blisters:2 years
HDPE bottles:Do not store above 30°C. Store in the original package and keep the bottle tightlyclosed.Aluminium blisters:Do not store above 30° C. Store in the original package.
|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.|
|Ergha Healthcare Ltd.,DamastownMulhuddartDublin 15|
9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE
AUTHORISATION13th May 2005/5th October 2005
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.