Consumer medicine information

Omeprazole Sandoz IV

Omeprazole

BRAND INFORMATION

Brand name

Omeprazole Sandoz IV

Active ingredient

Omeprazole

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Omeprazole Sandoz IV.

What is in this leaflet

This leaflet answers some common questions about Omeprazole Sandoz IV. It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you using this medicine against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Omeprazole Sandoz IV is used for

This medicine is used to treat and help heal peptic ulcers.

Depending on the position of the ulcer it is called a gastric or duodenal ulcer. A gastric ulcer occurs in the stomach. A duodenal ulcer occurs in the duodenum which is the tube leading out of the stomach.

Ulcers can be caused in part by too much acid being made in the stomach.

This medicine is also used to help prevent gastric or duodenal ulcers from coming back.

Reflux oesophagitis

This medicine is used to treat and prevent reflux oesophagitis. This can be caused by "washing back" (reflux) of food and acid from the stomach into the oesophagus (food pipe).

Reflux can cause a burning sensation in the chest rising up to the throat, also known as heartburn.

Zollinger-Ellison syndrome

This medicine is also used to treat a rare condition called Zollinger-Ellison syndrome, where the stomach produces very large amounts of acid, much more than in ulcers or reflux disease.

How Omeprazole Sandoz IV works

Omeprazole Sandoz IV belongs to a group of medicines called proton pump inhibitors. It works by decreasing the amount of acid made by the stomach. This does not stop food being digested in the normal way. It helps reduce the pain and also allows the ulcer to heal.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

There is no evidence that this medicine is addictive.

This medicine is available only with a doctor's prescription.

Before you are given Omeprazole Sandoz IV

When you must not take it

Do not take this medicine if:

  1. you have an allergy to:
  • omeprazole sodium
  • any of the ingredients listed at the end of this leaflet.
Some of the symptoms of an allergic reaction may include skin rash, itchiness, shortness of breath, swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing.
  1. you are currently taking a medicine containing the active substance nelfinavir, used to treat HIV infections.
Check with your doctor or pharmacist if you are taking any other medicines used to treat HIV infections, such as atazanavir.
  1. you are pregnant or breastfeeding, unless permitted by your doctor.
It is not yet known if it is safe for you to take this medicine while you are pregnant. It may affect your developing baby. It is also not yet known if this medicine passes into breast milk if you are breastfeeding. Ask your doctor about the risks and benefits involved in taking this medicine while pregnant or breastfeeding.
  1. you are also taking cilostazol.
Check with your doctor or pharmacist if you are taking cilostazol. This medicine will be affected by Omeprazole Sandoz IV.

Do not use this medicine after the expiry date printed on the pack has passed.

Do not use this medicine if the packaging is torn or shows signs of tampering.

Before you are given it

You must tell your doctor if:

  1. you have any allergies to:
  • omeprazole sodium
  • any medicine containing a proton-pump inhibitor
  • any of the ingredients listed at the end of this leaflet
  • any other substances, such as foods, preservatives or dyes.
  1. you are pregnant or intend to become pregnant.
Your doctor will discuss the risks and benefits of using this medicine during pregnancy.
  1. you are breastfeeding or intend to breastfeed.
This medicine is not recommended for use during breastfeeding.
  1. you have or have had any problems with your liver or other medical conditions.
  2. you are taking other medicines that may cause low levels of magnesium in the blood (hypomagnesaemia). For example diuretics.

If you have not told your doctor about any of the above, tell them before you are given Omeprazole Sandoz IV.

Taking other medicines

Do not take Omeprazole Sandoz IV if you are taking the following medicine:

cilostazol, a medicine used to treat intermittent claudication.

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and Omeprazole Sandoz IV may interfere with each other. These include:

  • ketoconazole, itraconazole, voriconazole - medicines used to treat fungal infection
  • diazepam - a medicine used to treat anxiety and some other conditions
  • phenytoin - a medicine used to treat epilepsy or fits
  • warfarin and clopidogrel - medicines used to prevent blood clots
  • clarithromycin or rifampicin - medicines used to treat infections
  • atazanavir and nelfinavir - medicines used to treat viral infection such as HIV
  • erlotinib or related medicines used to treat cancer
  • tacrolimus - used as immunosuppressant, adjunct to liver or kidney transplantation
  • St. John's wort - a medicine used to treat anxiety, stress, nervous tension and some other conditions.
  • digoxin - a medicine used to treat heart problems.

These medicines may be affected by Omeprazole Sandoz IV, or may affect how well it works. You may need different amounts of your medicine or you may need to use different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while using this medicine.

How Omeprazole Sandoz IV is given

Omeprazole Sandoz IV will be given to you in hospital by highly trained medical personnel.

It will be injected into a vein over a period of 20 to 30 minutes. This is called intravenous infusion.

Your doctor will decide what dose and how long you will receive this medicine.

In most patients, Omeprazole Sandoz IV relieves symptoms rapidly and it will be replaced with omeprazole capsules as soon as you are well enough to swallow them.

Omeprazole Sandoz IV is usually given once daily and may be increased to twice daily depending on your response.

Ask your doctor if you want to know more about the dose of Omeprazole Sandoz IV you receive.

If you have been given too much (overdose)

As Omeprazole Sandoz IV will be given to you under the supervision of your doctor, it is very unlikely that you will receive too much.

However, if you experience severe side effects after being given this medicine, tell your doctor immediately or go to the Accident and Emergency department of your nearest hospital. You may need urgent medical attention.

Symptoms of an omeprazole overdose may include severe nausea (feeling sick) or vomiting, diarrhoea, confusion, headache, dizziness, abdominal pain and depression.

While you are being given Omeprazole Sandoz IV

Things you must do

Tell your doctor immediately if you become pregnant while being given this medicine.

If you are about to be started on any new medicine, tell your doctor, dentist or pharmacist that you are being given Omeprazole Sandoz IV.

Tell all doctors, dentists and pharmacists who are treating you that you are being given Omeprazole Sandoz IV.

Things to be careful of

Be careful driving or operating machinery until you know how Omeprazole Sandoz IV affects you.

Side effects

Tell your doctor or nurse as soon as possible if you do not feel well while you are being given Omeprazole Sandoz IV.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need urgent medical attention if you get some of the side effects.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Ask your doctor, nurse or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • constipation
  • diarrhoea
  • nausea (feeling sick)
  • vomiting
  • headache
  • abdominal pain
  • excessive gas in stomach or bowel
  • dry or sore mouth
  • skin rash, itchy skin.

These side effects are usually mild.

Tell your doctor immediately if you notice any of the following:

  • joint pain, muscle pain or weakness
  • dizziness
  • tingling or numbness in the hands or feet
  • changes in sleep patterns & inability to sleep
  • unusual hair loss or thinning of hair
  • blurred vision or loss of vision
  • increase in breast size (males)
  • sleepiness or drowsiness
  • agitation, confusion, mood changes or hallucinations
  • depression or feeling of deep sadness & unworthiness
  • bruising or bleeding more easily than normal
  • increased sweating
  • signs of frequent infections such as fever, severe chills, sore throat or mouth ulcers
  • signs of liver inflammation including yellowing of the skin or eyes, feeling generally unwell, nausea, vomiting, loss of appetite
  • inability to get or maintain erection.
  • fractures, for example hip, wrist or spine.

These are serious side effects which may require medical attention. Serious side effects are rare.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital.

  • swelling of face, lips, mouth, tongue or throat which may cause difficulty in breathing
  • shortness of breath or difficulty in breathing
  • skin reaction which may include rash, itching, redness, blistering or peeling of the skin
  • ulcers, blisters or bleeding of the lips, eyes, mouth, nose and genitals
  • blood in urine
  • swelling of feet, hands and ankles.

These are very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are very rare.

Tell your doctor if you notice anything that is making you feel unwell.

Other side effects not listed above may occur in some people.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Other health problems may arise from the condition being treated itself rather than the treatment.

For this reason, contact your doctor immediately if you notice any of the following:

  • pain or indigestion during treatment with Omeprazole Sandoz IV
  • vomiting blood or food
  • passing black or blood-stained motions
  • unexpected weight loss.

After being given Omeprazole Sandoz IV

Storage

Omeprazole Sandoz IV will be stored in the pharmacy or on the hospital ward. It will be stored in a cool dry place where the temperature stays below 25°C, protected from light.

Product description

What it looks like

Omeprazole Sandoz IV is a white to almost white powder. The powder is mixed with normal saline or 5% glucose before being injected. The reconstituted solution is a clear, colourless solution.

Ingredients

Active ingredient:

Each vial contains 42.56mg omeprazole sodium (this is equal to 40mg omeprazole).

Inactive Ingredients:

  • disodium edetate
  • sodium hydroxide.

Omeprazole Sandoz IV does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Supplier

Sandoz Pty Ltd
ABN 60 075 449 553
54 Waterloo Road,
Macquarie Park, NSW 2113
Australia
Tel: 1800 726 369

Novartis New Zealand Ltd
Private Bag 65904 Mairangi Bay
Auckland 0754
New Zealand
Tel: 0800 354 335

This leaflet was revised in November 2017.

Australian Registration Number:

AUST R 127835

Published by MIMS March 2018

BRAND INFORMATION

Brand name

Omeprazole Sandoz IV

Active ingredient

Omeprazole

Schedule

S4

 

1 Name of Medicine

Omeprazole sodium.

2 Qualitative and Quantitative Composition

Each vial of Omeprazole Sandoz IV powder for injection contains omeprazole sodium, which occurs as a white or almost white powder, hygroscopic, freely soluble in water and in alcohol, soluble in propylene glycol, very slightly soluble in methylene chloride. The reconstituted solution appears as a clear, colourless solution.
Each 10 mL glass contains 42.56 mg omeprazole sodium equivalent to 40 mg omeprazole.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Omeprazole Sandoz IV 40 mg powder for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

Short-term use when omeprazole cannot be administered orally for or during the following conditions:
treatment of duodenal ulcer, gastric ulcer and ulcerative oesophagitis;
treatment of Zollinger-Ellison syndrome;
long-term prevention of relapse in healed severe reflux oesophagitis (grades 3 and 4) and gastric and duodenal peptic ulceration in patients proven to be Helicobacter pylori negative, whose ulceration is not associated with ingestion of NSAIDs, when oral therapy is not possible.
Omeprazole Sandoz IV should be replaced with oral therapy as soon as practicable.

4.2 Dose and Method of Administration

Dosage.

Omeprazole Sandoz IV should only be used where oral medication is inappropriate, e.g. in severely ill patients. Omeprazole Sandoz IV should be replaced with oral therapy as soon as practicable. If intravenous therapy is necessary for more than five days, consideration should be given to reducing the daily dose.
The product is for single use in one patient only.

Duodenal ulcer, gastric ulcer and ulcerative reflux oesophagitis.

Omeprazole Sandoz IV 40 mg given intravenously once daily is recommended. This produces an immediate decrease in intragastric acidity and a mean decrease over 24 hours of approximately 90%.

Zollinger-Ellison syndrome.

The recommended initial dose of Omeprazole Sandoz IV given intravenously is 60 mg daily. Higher daily doses, up to 240 mg daily, may be required. The dose should be adjusted according to individual response. When the dose exceeds 120 mg intravenously daily, it should be administered twice daily in equally divided amounts.

Method of administration.

Reconstitution.

Omeprazole Sandoz IV should be reconstituted with 100 mL of sodium chloride 0.9% or glucose 5% and infused over a period of 20 to 30 minutes.
Omeprazole Sandoz IV should be administered within 6 hours after reconstitution to reduce microbiological hazard. Omeprazole Sandoz IV is for one dose in one patient only. Discard any remaining contents. Omeprazole Sandoz IV may be added to plastic giving sets.

Dosage adjustment in.

Renal impairment.

The systemic bioavailability of omeprazole is not significantly altered in patients with reduced renal function and no dosage adjustment is required.

Hepatic impairment.

The rate of plasma elimination of omeprazole and its metabolites is decreased in patients with liver cirrhosis. However, no accumulation has been observed during the use of the recommended oral dose of omeprazole 20 mg daily and no adjustment to the normal dosage regimen is required (see Section 4.4 Special Warnings and Precautions for Use).

Elderly.

No dosage adjustment of Omeprazole Sandoz IV is necessary in the elderly.

Paediatric.

There is no experience with Omeprazole Sandoz IV in children.

4.3 Contraindications

Hypersensitivity to omeprazole, substituted benzimidazoles or any other ingredients.
Combination therapy with clarithromycin should not be used in patients with hepatic impairment.
Omeprazole, an inhibitor of CYP2C19, is contraindicated in patients taking cilostazol.
Omeprazole, like other proton pump inhibitors (PPIs) must not be used concomitantly with nelfinavir.

4.4 Special Warnings and Precautions for Use

As with all antisecretory agents, the presence of any alarm symptom (e.g. significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis or melaena) and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment with omeprazole may alleviate symptoms and delay diagnosis.

Hypomagnesaemia.

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.
Severe hypomagnesaemia has been reported in patients treated with PPIs like omeprazole. 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 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.
PPIs, especially if used in high doses and over long durations, may modestly increase the risk of hip, wrist and spine fracture, predominantly in the elderly or in the presence of other recognised risk factors. Observational studies suggest that PPIs may increase the overall risk of fracture. 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.

Antimicrobial resistance.

The development of antimicrobial resistance may have an adverse effect on eradication regimens. The clinical impact on eradication regimens for H. pylori has not been comprehensively studied.

Subacute cutaneous lupus erythematosus (SCLE).

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

CYP2C19 enzyme.

Approximately 3% of the Caucasian population and 15-20% of the Asian population lack a functional CYP2C19 enzyme and are called poor metabolisers. In these individuals the metabolism of omeprazole is most likely 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 3 to 5 times higher. The implications of these findings need to be addressed from clinical perspective.

Effects related to acid inhibition.

Decreased gastric acidity due to any means including PPIs 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.

Use in hepatic impairment.

Patients with impaired liver function show a markedly increased bioavailability, a reduced total plasma clearance and up to a four-fold prolongation of the elimination half-life. However, urinary recovery over 96 hours remains unchanged, indicating no accumulation of omeprazole or its metabolites. The normal dose of omeprazole 20 mg daily may be used in patients with severe liver disease (see Section 4.2 Dose and Method of Administration).

Use in the elderly.

No data available.

Paediatric use.

There is no experience with Omeprazole Sandoz IV in children.

Effects on laboratory tests.

Increased CgA level may interfere with investigations for neuroendocrine tumours. To avoid this interference, omeprazole treatment should be stopped for at least 5 days before CgA measurements (see Section 5 Pharmacological Properties).
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.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Absorption.

The decreased intragastric acidity during treatment with omeprazole and other PPIs might increase or decrease the absorption of drugs if the mechanism of absorption is influenced by gastric acidity.
Omeprazole produces a profound and sustained inhibition of gastric acid secretion. The absorption of compounds whose absorption depends on gastric pH may decrease during treatment with omeprazole. 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.

Metabolism.

Cytochrome P450 effects. Omeprazole is mainly metabolised via the hepatic cytochrome P450 system (CYP2C19) and may be expected to interact with the metabolism of other drugs metabolised by this enzyme.
Potential interactions.

Clopidogrel.

Clopidogrel is metabolised to its active metabolite by CYP2C19. Inhibition of CYP2C19 by omeprazole would be expected to result in reduced drug levels of the active metabolite of clopidogrel and a reduction in its antiplatelet activity and therefore its clinical efficacy. Concomitant use of omeprazole with clopidogrel should be discouraged.
Potential interactions that have been excluded. Results from a range of in vivo interaction studies with omeprazole versus other drugs indicate that omeprazole 20 to 40 mg, given repeatedly, has no influence on any other relevant isoforms of CYP, as shown by the lack of metabolic interaction with substrates for CYP1A2 (caffeine, phenacetin, theophylline), CYP2C9 (S-warfarin, piroxicam, diclofenac, and naproxen), CYP2D6 (metoprolol, propranolol), CYP2E1 (ethanol) and CYP3A (cyclosporin, lignocaine, quinidine and oestradiol).

Effects of omeprazole on other medicines.

Demonstrated interactions.

Diazepam.

Following dosing with omeprazole 40 mg once daily, the clearance of diazepam was decreased by 54% and the mean elimination half-life of diazepam was increased by 130%, with a consequent significant increase in plasma diazepam concentrations. For omeprazole 20 mg, the clearance of diazepam was decreased by approximately 25% in the majority of the population, while no change was detected in poor metabolisers. Consideration should be given to a reduction in diazepam dosage when Omeprazole Sandoz IV is co-prescribed.

Phenytoin.

Omeprazole 40 mg daily for seven days reduced plasma clearance of IV (intravenous) phenytoin by 15 to 20% and increased the elimination half-life by 27%. Monitoring of patients receiving phenytoin is recommended and a reduction of the phenytoin dose may be necessary. In a study that administered omeprazole 20 mg to patients with epilepsy, steady-state plasma levels of phenytoin were unchanged during omeprazole treatment.

Warfarin.

Concomitant administration of oral omeprazole 20 mg to patients on continuous treatment with warfarin caused a slight though statistically significant increase in the plasma concentration of the R-enantiomer of warfarin. Plasma concentrations of the more potent S-enantiomer were not affected and no change in warfarin's anticoagulant activity was observed.
It is recommended that coagulation tests be monitored closely when initiating or ceasing Omeprazole Sandoz IV in patients co-prescribed warfarin.

Cilostazol.

Omeprazole given in doses of 40 mg daily to healthy subjects in a cross over study for 7 days increased Cmax and AUC for cilostazol by 18% and 26% respectively, and one of its active metabolites by 29% and 69%, respectively (see Section 4.3 Contraindications).

Methotrexate.

When given together with PPIs, 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.

Antiretroviral drugs.

Omeprazole has been reported to interact with some antiretroviral drugs. The clinical importance and the mechanisms behind these interactions are not always known. Increased gastric pH during omeprazole treatment may change the absorption of the antiretroviral drug. Other possible interaction mechanisms are via CYP2C19.
For some antiretroviral drugs, such as atazanavir and nelfinavir, decreased serum levels have been reported when given together with omeprazole. Concomitant administration of omeprazole and drugs such as atazanavir is not recommended. Concomitant administration with nelfinavir is contraindicated (see Section 4.3 Contraindications). For other antiretroviral drugs, such as saquinavir, elevated serum levels have been reported. There are also some antiretroviral drugs of which unchanged serum levels have been reported when given with omeprazole.

Tacrolimus.

Concomitant administration of omeprazole and tacrolimus may increase the serum levels of tacrolimus.

St. John’s wort.

Because of potential clinically significant interaction, St. John’s Wort should not be used concomitantly with omeprazole.

Digoxin.

Concomitant treatment with omeprazole (20 mg daily) and digoxin in healthy subjects increased the bioavailability of digoxin by 10% (up to 30% in two out of ten subjects). 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 then be reinforced.

Effects of other medicines on omeprazole.

Demonstrated interactions. Drugs known to induce CYP2C19 or CYP3A4 or both (such as rifampicin) may lead to decreased omeprazole serum levels by increasing the rate of metabolism of omeprazole.
Drugs known to inhibit CYP2C19 or CYP3A4 or both (such as clarithromycin or voriconazole) may lead to increased omeprazole serum levels by decreasing the rate of metabolism of omeprazole. Concomitant administration of omeprazole and voriconazole, a CYP2C19 and CYP3A4 inhibitor, resulted in more than doubling of the omeprazole exposure. Plasma concentrations of omeprazole are increased during concomitant administration with clarithromycin.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There was no evidence of an adverse effect on fertility following administration of omeprazole to male and female rats at doses up to 320 mg/kg/day orally (16-fold anticipated exposure at the clinical oral dose of 40 mg/day, based on plasma AUC) and 100 mg/kg/day intravenously (14-fold anticipated exposure at the clinical intravenous dose of 40 mg/day, based on plasma AUC). Oral administration to male rats prior to mating and to female rats prior to and throughout gestation at seven-fold clinical exposure was associated with embryofetal toxicity.
(Category B3)
Results from three prospective epidemiological studies indicate that while there was no increase in the overall malformation rates compared with controls, the data indicated a potentially higher rate of cardiac defects in the omeprazole group.
There was no evidence of teratogenicity following administration of omeprazole to pregnant rats and rabbits during the period of organogenesis. Doses in rats were associated with systemic exposures of up to 16 and 14-fold (oral and intravenous administration, respectively) the anticipated exposure at the clinical dose of 40 mg/day (based on plasma AUC). Studies in rats did not demonstrate embryotoxicity apart from increased locomotor activity in prenatally exposed offspring at systemic exposures approximating clinical exposure, based on plasma AUC. In rabbits, oral doses were associated with systemic exposure less than clinical exposure (plasma AUC) and intravenous doses were up to 13-fold the 40 mg/day clinical dose (on a mg/m2 basis). Embryofetal toxicity and maternotoxicity occurred at doses associated with less than clinical exposures.
 Omeprazole and its metabolites are excreted in milk in rats but it is not known if this occurs in humans. In rats, reduced offspring postpartum growth rate was observed following administration of omeprazole during late gestation and throughout lactation at oral doses of 138 mg/kg/day and above (seven-fold anticipated exposure at the clinical dose of 40 mg/day, based on plasma AUC) and intravenous doses of 3.2 mg/kg/day and above (less than clinical exposure). It is recommended that omeprazole not be used in breastfeeding mothers.

4.7 Effects on Ability to Drive and Use Machines

No effects have been observed. Adverse drug reactions such as somnolence, dizziness and visual disturbances may occur. If affected, patients should not drive or operate machinery.

4.8 Adverse Effects (Undesirable Effects)

Omeprazole IV is well tolerated. Most adverse reactions have been mild and transient and there has been no consistent relationship with treatment.
The most common side effects (1-10% of patients) are headache, abdominal pain, constipation, diarrhoea, flatulence and nausea/ vomiting.
The types of adverse events reported with omeprazole IV have been of a similar spectrum to oral omeprazole.
Doses of up to 200 mg omeprazole IV have not been associated with any dose related increase in adverse events.
The following adverse drug reactions have been identified or suspected in the clinical trials programme for omeprazole and postmarketing.
Adverse reactions within each body system are listed in descending order of frequency: very common: ≥ 10%; common: ≥ 1% and < 10%; uncommon: ≥ 0.1% and < 1%; rare: ≥ 0.01% and < 0.1%; very rare: < 0.01%). These include the following:

Gastrointestinal disorders.

Common: diarrhoea, constipation, abdominal pain, nausea/vomiting, flatulence, fundic gland polyps (benign).
Rare: stomatitis, gastrointestinal candidiasis, microscopic colitis, dry mouth.
Very rare: dyspepsia, haemorrhagic necrotic gastritis (reported in children).

Psychiatric disorders.

Common: insomnia.
Rare: reversible mental confusion, agitation, aggression, light headedness, depression and hallucinations, predominantly in severely ill patients or elderly patients.

Nervous system disorders.

Common: headache, drowsiness, somnolence.
Uncommon: dizziness, paraesthesia, taste disturbances.

Hepatobiliary disorders.

Uncommon: increased liver enzymes.
Rare: encephalopathy in patients with pre-existing severe liver disease, hepatitis with or without jaundice, hepatic failure.

Skin and subcutaneous tissue disorders.

Uncommon: rash, skin eruptions, urticaria and/or pruritus, alopecia, erythema multiforme, dermatitis.
Rare: photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN).
Not known: subacute cutaneous lupus erythematosus (see Section 4.4 Special Warnings and Precautions for Use).

Immune system disorders.

Rare: hypersensitivity reactions, e.g. angioedema, fever, bronchospasm, interstitial nephritis, anaphylactic reaction/shock, allergic vasculitis.

Respiratory, thoracic and mediastinal disorders.

Rare: bronchospasm.
Very rare: dyspnoea.

Renal and urinary disorders.

Rare: interstitial nephritis.
Very rare: impaired renal function, including nephrosis.

Metabolism and nutrition disorders.

Rare: hyponatraemia.
Very rare: weight increase, hypomagnesaemia and hypokalaemia (reported in children).
Severe hypomagnesaemia may result in hypocalcaemia. Hypomagnesaemia may also result in hypokalaemia.

General disorders and administration site conditions.

Uncommon: peripheral oedema, malaise.
Rare: increased sweating.

Reproductive system and breast disorders.

Rare: gynaecomastia.
Very rare: impotence (although causality has not been established).

Blood and lymphatic system disorders.

Rare: leucopenia, thrombocytopenia, agranulocytosis, pancytopenia.

Musculoskeletal and connective tissue disorders.

Uncommon: fracture of the hip, wrist or spine.
Rare: arthralgia, muscular weakness, joint pain, myalgia.

Eye disorders.

Rare: blurred vision.
Loss of vision has been reported in isolated cases in association with the use of intravenous omeprazole. These cases involved critically ill patients who received high doses of omeprazole as an intravenous bolus injection. A causal relationship has not been established.

Ear and labyrinth disorders.

Uncommon: vertigo.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

Rare reports have been received of overdosage with omeprazole. 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 from overdosage with omeprazole. Also apathy, depression and confusion have been described in single cases. The symptoms described in connection to omeprazole overdosage have been transient, and no serious clinical outcome due to omeprazole has been reported.
There is no information at present regarding poisoning or overdosage and no specific recommendations for treatment can be given. In suspected cases of overdosage, treatment should be supportive and symptomatic.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Omeprazole reversibly reduces gastric acid secretion by specifically inhibiting the gastric enzyme H+/K+ ATPase, the proton pump, in the acid environment of the intracellular canaliculi within the parietal cell. This effect of omeprazole on the final step of the gastric acid formation process is dose dependent and effectively inhibits both basal acid secretion and stimulated acid secretion, irrespective of the stimulus to acid production.
Omeprazole has no effect on acetylcholine or histamine receptors. No clinically significant pharmacodynamic effects, other than those explained by the effect on acid secretion, have been observed.

Effect on gastric acid secretion.

Oral dosing with omeprazole 20 mg once daily provides rapid and effective reduction of gastric acid secretion. After a single dose the onset of antisecretory effect occurs within one hour and is maximal within two hours. With repeated once daily dosing the maximum effect is usually achieved within four days of commencing treatment.
A single dose of 40 mg intravenously will achieve immediate and maximal control of acid production, similar to that observed following five days continuous oral administration of omeprazole 20 mg.
A mean decrease of approximately 80% in 24 hour intragastric acidity is maintained in duodenal ulcer patients treated with an oral dose of omeprazole 20 mg. Omeprazole produces a mean decrease in peak pentagastrin stimulated acid output of approximately 70% 24 hours after dosing. When the drug is discontinued, secretory activity returns to approximately 50% of maximum after 24 hours and gradually returns to normal over three to five days.

Other effects related to acid inhibition.

Decreased gastric acidity due to any means including proton pump inhibitors (PPIs) 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.
In some patients, fasting serum gastrin levels have been noted to rise two to fourfold during treatment with omeprazole. Up to 3% of patients have values exceeding 400 picogram/mL.
During treatment with antisecretory medicinal products, serum gastrin increases in response to the decreased acid secretion. Also Chromogranin A (CgA) increases due to decreased gastric acidity. The increased CgA level may interfere with investigations for neuroendocrine tumours.
Available published evidence suggests that PPIs should be discontinued between 5 days and 2 weeks prior to CgA measurements. This is to allow CgA levels that might be spuriously elevated following PPI treatment to return to reference range.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Distribution.

The plasma protein binding of omeprazole is approximately 95%. The inhibition of acid secretion is related to the area under the plasma concentration time curve (AUC) but not to the actual plasma concentration at any given time.

Metabolism.

Omeprazole is entirely metabolised by the cytochrome P450 system (CYP), mainly in the liver. Identified metabolites in plasma are the sulfone, the sulfide and hydroxyomeprazole. These metabolites have no significant effect on acid secretion. The average half-life of the terminal phase of the plasma concentration time curve following IV administration of omeprazole is approximately 40 minutes; the total plasma clearance is 0.3 to 0.6 L/minute. There is no change in half-life during repeated dosing.

Excretion.

About 80% of the metabolites are excreted in urine and the remainder in faeces. The two main urinary metabolites are hydroxyomeprazole and the corresponding carboxylic acid.
In repeat dose pharmacokinetic studies, a 10 mg dose of omeprazole IV (intravenously) was demonstrated to be bioequivalent to omeprazole 20 mg when administered orally.
Intravenous omeprazole produces a dose dependent inhibition of pentagastrin stimulated acid secretion in humans. A single dose of 10 mg IV demonstrates a similar effect on acid secretion as that observed following a single dose of oral omeprazole 20 mg. The effect of a single IV dose of omeprazole 40 mg results in an immediate reduction of intragastric acidity and a mean decrease over 24 hours of approximately 90% in patients with duodenal ulcer disease. This is a similar response to that seen following repeated oral dosing with 20 mg once daily.
Therefore, although a dose of omeprazole 10 mg IV is pharmacokinetically and pharmacodynamically equivalent to omeprazole 20 mg orally, a dose of 40 mg IV is required to achieve rapid control of acid production. This therapeutic goal is desirable in patients for whom omeprazole IV is indicated, as they are generally severely ill and require rapid stabilisation of their symptoms.

5.3 Preclinical Safety Data

Genotoxicity.

Omeprazole has been subjected to a battery of in vitro and in vivo genotoxicity tests to examine the mutagenic, clastogenic and DNA damaging potential of the drug. The in vitro assays include the Ames test, mouse lymphoma TK locus forward mutation assay and a chromosome aberration test in human lymphocytes. The in vivo tests were a chromosome aberration test in mouse bone marrow, an alkaline elution/ rat liver DNA damage assay and two mouse micronucleus tests. No evidence of significant genotoxicity was seen in the tests.

Carcinogenicity.

In a two year carcinogenicity study in rats, omeprazole at daily doses of 13.8, 44.0 and 140.8 mg/kg/day produced gastric enterochromaffin-like (ECL) cell hyperplasia and carcinoid tumours in a dose related manner in both male and female rats. The incidence of these effects was markedly higher in female rats.
The same effects were seen in an additional two year study in female rats at daily doses of 1.7, 3.4 and 13.8 mg/kg/day. A no effect dose was not established in female rats in the dose ranges studied.
In mice, a 78 week carcinogenicity study was performed according to relevant regulatory and scientific standards. No gastric ECL cell carcinoids were seen. However, longer-term studies have not been performed in this species.
Hypergastrinaemia, ECL cell hyperplasia and gastric carcinoids have also been produced in the rat by other treatments or procedures not related to omeprazole. These include the following.

(a) Exogenous gastrin infusion.

Subcutaneous infusion of gastrin-17 has resulted in a significant hyperplasia of ECL cells following treatment for one month.

(b) H2-receptor antagonists.

In rats administered 2 g/kg/day of ranitidine in their diet over 106 weeks, argyrophilic cell hyperplasia was observed in 37% of the animals and gastric carcinoids were found in 19% of the treated group.

(c) Surgical resection of the acid producing oxyntic mucosa.

In rats in which 75% of the stomach corpus was surgically removed, 26 of 75 animals developed ECL cell carcinoids during the 124 week study.
These findings show that the development of ECL cell carcinoids in the rat is directly related to hypergastrinaemia rather than a direct effect of omeprazole on the ECL cell.
Omeprazole may also affect other cells in the gastrointestinal tract (for example, G cells) either directly or by inducing sustained hypochlorhydria but this possibility has not been extensively studied.

6 Pharmaceutical Particulars

6.1 List of Excipients

Omeprazole Sandoz IV powder for injection also contains disodium edetate and sodium hydroxide.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.
For information on interactions with other medicines and other forms of interactions, see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Powder.

Store below 25°C. Protect from light.

Reconstituted solution.

Store below 25°C. Protect from light.
Use within 6 hours after reconstitution.

6.5 Nature and Contents of Container

Each 10 mL glass vial with rubber stopper and aluminium cap contains 42.56 mg omeprazole sodium equivalent to 40 mg omeprazole. Pack size of 5 vials.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

The chemical name of omeprazole sodium is sodium 5-methoxy-2-[(RS)-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulphinyl]-1H-benzimidazole. Its empirical formula is C17H18N3NaO3S.H2O (MW: 385.4).

Chemical structure.

Its structural formula is:

CAS number.

95510-70-6.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes