ASANDOZ SZ00000LT000

PACKAGE LEAFLET: INFORMATION FOR THE USER Omeprazole 40mg Powder for Solution for Injection and Solvent for Omeprazole 40mg Powder for Solution for Injection

Omeprazole sodium

Read all of this leaflet carefully before you

start using this medicine.

•    Keep this leaflet. You may need to read it again.

•    If you have any further questions, ask your doctor or pharmacist.

•    If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

1.    What Omeprazole Injection is and what it is used for

2.    Before Omeprazole Injection is used

3.    How Omeprazole Injection is used

4.    Possible side effects

5.    How to store Omeprazole Injection

6.    Further information

1. What Omeprazole Injection is and what it is used for

Omeprazole 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 powder and solvent for solution for injection can be used as an alternative to oral therapy.

2. Before Omeprazole Injection is used

You must not be given Omeprazole

•    if you are allergic (hypersensitive) to omeprazole or any of the other ingredients of Omeprazole

•    if you are allergic to other proton pump inhibitor medicines (e.g. pantoprazole, lansoprazole, rabeprazole, esomeprazole)

•    if you are taking a medicine containing nelfinavir (used for HIV infection).

If you are not sure, talk to your doctor, nurse or pharmacist before you are given this medicine.

Take special care with Omeprazole

Omeprazole may hide the symptoms of other diseases. Therefore, if any of the following happen to you before you are given Omeprazole or after you are given 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.

Using other medicines

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

You must not be given Omeprazole 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 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

•    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

•    Rifampicin (used to treat tuberculosis)

•    Atazanavir (used to treat HIV infection)

•    Tacrolimus (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)).

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

Pregnancy and breast-feeding

Before you are given Omeprazole, tell your doctor if you are pregnant or trying to get pregnant. Your doctor will decide whether you can be given Omeprazole during this time.

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 if you are breast-feeding.

Driving and using machines

Omeprazole 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.

Other side effects include:

Common side effects

•    Headache

•    Effects on your stomach or gut: diarrhoea, stomach pain, constipation, wind (flatulence)

•    Feeling sick (nausea) or being sick (vomiting).

Uncommon side effects

•    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

•    Fracture in the hip, wrist or spine.¹

Rare side effects

•    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

•    Changes in blood count including agranulocytosis (lack of white blood cells)

•    Aggression

•    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

•    Low levels of magnesium in the blood.²

¹Taking a proton pump inhibitor like Omeprazole, 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).

²If you are on Omeprazole 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.

Irreversible visual impairment has been reported in isolated cases of critically ill patients who have received Omeprazole intravenous injection, especially at high doses, but no causal relationship has been established.

Omeprazole 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.

5. How to store Omeprazole Injection

3. How Omeprazole Injection is used

•    Omeprazole can be given to adults including the elderly

•    There is limited experience with Omeprazole for intravenous use in children.

Being given Omeprazole

•    Omeprazole will be given to you by a doctor who will decide how much you need

•    The medicine will be given to you as an injection into one of your veins.

If you are given more Omeprazole than you

should

If you think you have been given too much

Omeprazole, talk to your doctor straight away.

Keep out of the reach and sight of children.

Do not store above 25°C. Store in the original package in order to protect from light.

Do not use Omeprazole 40 mg powder for solution for injection after the expiry date which is state on the label after EXP. The expiry date refers to the last day of that month.

After preparation of the solution by your doctor or nurse, it must be stored below 25°C and used within four hours.

The reconstituted solution should not be used if particles are present.

The contents of the vial is meant for single use; any product that has remained in the vial has to be discarded. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist howto dispose of medicines no longer required. These measures will help to protect the environment.

6. Further information

4. Possible side effects

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

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

•    Sudden wheezing, swelling of your lips, tongue and throat or body, rash, fainting or difficulties to swallow (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.

Side effects may occur with certain frequencies, which are defined as follows:

What Omeprazole contains

Each vial of powder for solution for injection contains the active ingredient omeprazole sodium, equivalent to omeprazole 40 mg.

Each vial also contains sodium hydroxide.

Each vial is for one injection when mixed with one ampoule containing the solvent for injection. The solvent for injection contains macrogol 400, citric acid monohydrate and water for injections.

What Omeprazole looks like and contents of the pack

The powder for solution for injection is a white to almost white powder. The solvent for solution for injection is clear solution.

Omeprazole powder and solvent for solution for injection are available in packsizes of 1,5 and 10.

Marketing Authorisation Holder:

Sandoz Ltd,

Frimley Business Park, Frimley,

Camberley, Surrey, GU16 7SR, UK.

Manufacturer:

Lek Pharmaceuticals d.d.,

Verovskova 57, 1526 Ljubljana, Slovenia.

This leaflet was last approved in 04/2012 (to be

amended after approval).

Sandoz Ltd,

Frimley Business Park, Frimley, Camberley, Surrey, GU 16 7SR, United Kingdom.

T: 01276 698020 F: 01276 698324 W: www.uk.sandoz.com E: sandoz.artwork@me.com

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The following information is intended for medical or healthcare professionals only:

1.    Name of the medicinal product

Omeprazole 40 mg powder and solvent for solution for injection.

2.    Qualitative and quantitative composition

Each vial of powder for injection contains omeprazole sodium, equivalent to 40 mg omeprazole.

For a full list of excipients, see section 6.1.

4.1.    Therapeutic indications

Omeprazole for intravenous use is indicated as an alternative to oral therapy for the following indications:

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 esophagitis

•    Long-term management of patients with healed reflux esophagitis

•    Treatment of symptomatic gastro-esophageal reflux disease

•    Treatment of Zollinger-Ellison syndrome.

4.2.    Posology and method of administration

Posology

Alternative to oral therapy In patients where the use of oral medicinal products is inappropriate, Omeprazole IV 40 mg once daily is recommended. In patients with Zollinger-Ellison Syndrome the recommended initial dose of Omeprazole given intravenously is 60 mg daily. Higher daily doses may be required and the dose should be adjusted individually. When doses exceed 60 mg daily, the dose should be divided and given twice daily.

Omeprazole solution for injection must be given only as an intravenous injection and it must not be added to infusion solutions. After reconstitution the injection should be given slowly over a period of at least 2.5 minutes at a maximum rate of 4 ml per minute. For instructions on reconstitution of the product before administration, see section 6.6.

Special populations Impaired renal function

Dose adjustment is not needed in patients with impaired renal function.

Impaired hepatic function

In patients with impaired hepatic function a daily

dose of 10-20 mg may be sufficient.

Elderly (> 65 years old)

Dose adjustment is not needed in the elderly.

Paediatric patients

There is limited experience with Omeprazole for intravenous use in children.

4.3.    Contraindications

Hypersensitivity to omeprazole, substituted benzimidazoles or to any of the excipients.

Omeprazole like other proton pump inhibitors (PPIs) should not be used concomitantly with nelfinavir (see section 4.5).

4.4.    Special warnings and precautions for use

In the presence of any alarm symptoms (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.

Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter.

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

For patients expected to be on prolonged treatment or who take proton pump inhibitors with digoxin or drugs that may cause hypomagnesaemia (e.g., diuretics), health care professionals should consider measuring magnesium levels before starting proton pump inhibitor 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.

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

Fffects of omeprazole on the pharmacokinetics of other active substances

Active substances with pH dependent absorption

The decreased intragastric acidity during treatment with omeprazole might increase or decrease the absorption of active substances with a gastric pH dependent absorption.

Nelfinavir, atazanavir

The plasma levels of nelfinavir and atazanavir are decreased in case of co-administration with omeprazole.

Concomitant administration of omeprazole with nelfinavir is contraindicated (see section 4.3). Co-administration of omeprazole (40 mg once daily) reduced mean nelvinavir exposure by ca. 40% and the mean exposure of the pharmacologically active metabolite M8 was reduced by ca. 75-90%. The interaction may also involve CYP2C19 inhibition.

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

In a crossover clinical study, clopidogrel (300 mg loading dose followed by 75 mg/day) alone and with omeprazole (80 mg at the same time as clopidogrel) were administered for 5 days. The exposure to the active metabolite of clopidogrel was decreased by 46% (Day 1) and 42% (Day 5) when clopidogrel and omeprazole were administered together. Mean inhibition of platelet aggregation (IPA) was diminished by 47% (24 hours) and 30% (Day 5) when clopidogrel and omeprazole were administered together. In another study it was shown that administering clopidogrel and omeprazole at different times did not prevent their interaction that is likely to be driven by the inhibitory effect of omeprazole on CYP2C19. Inconsistent data on the clinical implications of this PK/PD interaction in terms of major cardiovascular events have been reported from observational and clinical studies.

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 Cmax 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.

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.

6. PHARMACEUTICAL PARTICULARS

6.1.    List of excipients

Powder for solution for injection: sodium hydroxide Solvent for solution for injection: Macrogol 400, citric acid monohydrate, water for injections.

6.2.    Incompatibilities

Omeprazole powder for solution for injection must not be mixed with other medicinal products, except the solvent for injection mentioned in section 6.6.

The reconstituted product must not be mixed with other medicinal products.

6.3.    Shelf life

Powder for solution for injection: 2 years.

Solvent for solution for injection: 3 years. Reconstituted solution: 4 hours when stored below 25°C.

6.4.    Special precautions for storage

Powder and solvent for solution for injection: do not store above 25°C. Store in the original package in order to protect from light

For storage conditions of the reconstituted medicinal product, see section 6.3.

Chemical and physical in-use stability has been demonstrated for 4 hours at 25°C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C. unless reconstitution has taken place in controlled and aseptic conditions.

6.5.    Nature and contents of container

Powder for solution for injection:

10 ml colourless glass vial Type I with a rubber stopper, and an aluminium cramping cap with propylene cap.

Solvent for solution for injection:

10 ml colourless glass ampoule Type I.

Pack sizes: 1, 5 or 10.

Not all pack sizes may be marketed

6.6.    Instructions for use and handling

One vial with powder for solution for injection should be mixed with one ampoule containing 10 ml of the solvent for solution for injection. A clear solution should be obtained. Omeprazole powder for injection should only be dissolved with the solvent for injection provided. No other solvents for intravenous injection should be used.

Do not use if any particles are present in the reconstituted solution.

The reconstituted solution is for single use only.

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

SZ00000LT000

Sandoz Ltd,

Frimley Business Park, Frimley, Camberley, Surrey, GU 16 7SR, United Kingdom.

T: 01276 698020 F: 01276 698324 W: www.uk.sandoz.com E: sandoz.artwork@me.com

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