Consumer medicine information

Omeprazole-WGR

Omeprazole

BRAND INFORMATION

Brand name

Omeprazole-WGR

Active ingredient

Omeprazole

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Omeprazole-WGR.

SUMMARY CMI

Omeprazole-WGR

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using OMEPRAZOLE-WGR?

OMEPRAZOLE-WGR contains the active ingredient omeprazole. OMEPRAZOLE-WGR is used to is used to treat and prevent gastro-oesophageal reflux disease (GORD) and reflux oesophagitis from returning. It is also used to treat peptic ulcers; peptic ulcers associated with helicobacter pylori infection; peptic ulcers associated with non-steroidal anti-inflammatory drugs (NSAIDs); and a rare condition called Zollinger-Ellison syndrome. For more information, see Section 1. Why am I using Omeprazole-WGR? in the full CMI.

2. What should I know before I use OMEPRAZOLE-WGR?

Do not use if you have ever had an allergic reaction to OMEPRAZOLE-WGR or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding. For more information, see Section 2. What should I know before I use OMEPRAZOLE-WGR? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with OMEPRAZOLE-WGR and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use OMEPRAZOLE-WGR?

  • Follow all directions given to you by your doctor or pharmacist
  • Take one OMEPRAZOLE-WGR tablet at the same time each day
  • Swallow the tablet whole with a glass of water. Do not crush or chew the tablet

More instructions can be found in Section 4. How do I use OMEPRAZOLE-WGR? in the full CMI.

5. What should I know while using OMEPRAZOLE-WGR?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using OMEPRAZOLE-WGR
  • Tell your doctor if you become pregnant whilst taking OMEPRAZOLE-WGR
  • Tel your doctor is your symptoms return
Things you should not do
  • Do not take OMEPRAZOLE-WGR to treat any other complaints unless your doctor tells you to
  • Do not stop taking OMEPRAZOLE-WGR or change the dosage without checking with your doctor
Driving or using machines
  • Be careful before you drive or operate machinery until you know how OMEPRAZOLE-WGR affects you
Drinking alcohol
  • Tell your doctor if you drink alcohol
Looking after your medicine
  • Keep OMEPRAZOLE-WGR in a cool, dry place where the temperature stays below 25°C
  • Keep OMEPRAZOLE-WGR tablets in the blister pack until it is time to take them

For more information, see Section 5. What should I know while using OMEPRAZOLE-WGR? in the full CMI.

6. Are there any side effects?

Common side effects include diarrhoea, constipation, abdominal pain, nausea/vomiting, flatulence and headache. Call your doctor straight away, or go straight to the Emergency Department if you have swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing; skin reaction including rash, redness, blistering or peeling of the skin; ulcers, blisters or bleeding of the lips, eyes, mouth, nose or genitals; swelling of hands, feet or ankles; blood in the urine; signs of liver inflammation including yellowing of the skin or eyes, feeling generally unwell, nausea, vomiting, loss of appetite; skin reaction, especially in sun exposed areas, with joint pain.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Omeprazole-WGR

Active ingredient: omeprazole

Consumer Medicine Information (CMI)

This leaflet provides important information about using OMEPRAZOLE-WGR. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using OMEPRAZOLE-WGR.

Where to find information in this leaflet:

1. Why am I using OMEPRAZOLE-WGR?
2. What should I know before I use OMEPRAZOLE-WGR?
3. What if I am taking other medicines?
4. How do I use OMEPRAZOLE-WGR?
5. What should I know while using OMEPRAZOLE-WGR?
6. Are there any side effects?
7. Product details

1. Why am I using OMEPRAZOLE-WGR?

OMEPRAZOLE-WGR contains the active ingredient omeprazole. OMEPRAZOLE-WGR belongs to a group of medicines called proton pump inhibitors. It works by reducing the amount of acid made by the stomach, to give relief of symptoms and allow healing to take place. This does not stop food being digested in the normal way.

OMEPRAZOLE-WGR is used to treat the following:

Peptic Ulcers

OMEPRAZOLE-WGR tablets are used to treat peptic ulcers and also to help prevent them from coming back.

These ulcers can be caused by the stomach producing too much acid. Depending on the location of the ulcer it is called a gastric or duodenal ulcer. A gastric ulcer occurs in the stomach and a duodenal ulcer occurs in the tube leading out of the stomach, also known as the duodenum.

Peptic Ulcers associated with Helicobacter pylori infection

Most people with a peptic ulcer have been found to have the bacteria Helicobacter pylori in their stomach. OMEPRAZOLE-WGR taken together with two antibiotics will kill the bacteria and let your ulcer heal. It is possible that the antibiotics may not always kill Helicobacter pylori.

Peptic Ulcers associated with Non-steroidal Anti-inflammatory Drugs (NSAIDs)

Some peptic ulcers are caused by taking medicines known as non-steroidal anti-inflammatory drugs. These medicines are commonly taken to treat arthritis and other inflammatory conditions.

OMEPRAZOLE-WGR can be used to heal and prevent ulcers associated with NSAIDs.

Reflux Oesophagitis

OMEPRAZOLE-WGR is used to treat and prevent the symptoms of reflux oesophagitis.

This condition is caused by the washing back, or reflux, of food and acid from the stomach into the oesophagus. Symptoms include a burning sensation in the chest rising up to the throat, also known as heartburn.

Zollinger-Ellison Syndrome

OMEPRAZOLE-WGR is used to treat this rare condition where the stomach produces excessive amounts of acid.

Your doctor may have prescribed OMEPRAZOLE-WGR for another reason.

OMEPRAZOLE-WGR is available only with a doctor's prescription.

There is no evidence that OMEPRAZOLE-WGR is addictive.

2. What should I know before I use OMEPRAZOLE-WGR?

Warnings

Do not use OMEPRAZOLE-WGR if:

  • You are allergic to omeprazole, or any of the ingredients listed at the end of this leaflet. Some of the symptoms of an allergic reaction may include skin rash, itching or hives; swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing; wheezing or shortness of breath.
  • Always check the ingredients to make sure you can use this medicine.
  • You are allergic to medicines containing a proton pump inhibitor
  • You are taking cilostazol (a medicine used to treat intermittent claudication) as it will be affected by OZEMP

Do not take OMEPRAZOLE-WGR if the expiry date printed on the pack has passed.

Do not take OMEPRAZOLE-WGR if the packaging shows signs of tampering or the tablets do not look quite right.

Check with your doctor if you:

  • take any medicines for any other condition
  • are allergic to any other medicines, foods, dyes or preservatives
  • any problems with your liver
  • been diagnosed with osteoporosis
  • have any other medical conditions
  • if you have ever had a skin reaction after treatment with a medicine similar to OMEPRAZOLE-WGR that reduces stomach acid

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Do not take OMEPRAZOLE-WGR if you are pregnant or breastfeeding unless your doctor says so. Ask your doctor about the risks and benefits involved.

Check with your doctor if you are pregnant or intend to become pregnant. It is not known if it is safe for you to take OMEPRAZOLE-WGR while you are pregnant. It may affect your baby.

Talk to your doctor if you are breastfeeding or intend to breastfeed. It is not known if your baby can take in OMEPRAZOLE-WGR from breast milk if you are breastfeeding.

3. What if I am taking other medicines?

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

Do not take OMEPRAZOLE-WGR if you are taking the following medicine:

  • Cilostazol (medicine used to treat intermittent claudication)

Some medicines may interfere with OMEPRAZOLE-WGR and affect how it works.

  • phenytoin (a medicine used to treat epilepsy or fits)
  • methotrexate (a medicine used to treat arthritis and some types of cancer)
  • warfarin and clopidogrel (a medicine used to prevent blood clots)
  • digoxin (a medicine used to treat heart conditions)
  • diazepam (a medicine used to treat anxiety and some other conditions)
  • St John's wort (a herbal remedy used to treat mood disorders)
  • ketoconazole, itraconazole or voriconazole (medicines used to treat certain fungal infections)
  • medicines to treat infections such as clarithromycin or rifampicin
  • anti-viral medicines such as atazanavir and nelfinavir, used to treat infections such as HIV
  • tacrolimus and mycophenolate, immunosuppressants, medicines used to assist in organ transplants
  • erlotinib or related medicines used to treat cancer

These medicines may be affected by OMEPRAZOLE-WGR or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines. Your doctor can tell you what to do if you are taking any other medicines.

If you have not told your doctor about any of the above, tell them before you start taking OMEPRAZOLE-WGR.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect OMEPRAZOLE-WGR.

4. How do I use OMEPRAZOLE-WGR?

How much to take / use

  • The usual dose is 20 mg a day.
  • Your doctor may vary this dose depending on your condition.
  • The dose varies from patient to patient. Your doctor will decide the right dose for you.
  • Follow all directions given to you by your doctor and pharmacist carefully. They may differ from the information contained in this leaflet.
  • Follow the instructions provided and take OMEPRAZOLE-WGR until your doctor tells you to stop.
  • Swallow the tablets whole with a glass of water. Do not crush or chew the tablets.

When to take / use OMEPRAZOLE-WGR

  • OMEPRAZOLE-WGR should be taken at the same time each day.
  • Keeping a regular time for tablets will help to remind you to take them
  • OMEPRAZOLE-WGR can be taken with or without food

Keep taking OMEPRAZOLE-WGR for as long as your doctor recommends. In most patients, OMEPRAZOLE-WGR relieves symptoms rapidly and healing is usually complete within 4 weeks.

If you forget to use OMEPRAZOLE-WGR

OMEPRAZOLE-WGR should be used regularly at the same time each day. If you miss your dose at the usual time, take the missed dose as soon as you remember, and then go back to taking your tablets as you would normally.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose you missed.

If you use too much OMEPRAZOLE-WGR

If you think that you have used too much OMEPRAZOLE-WGR, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

If you take too much OMEPRAZOLE-WGR you may experience nausea, vomiting, dizziness, abdominal pain, diarrhoea and/or headache.

5. What should I know while using OMEPRAZOLE-WGR?

Things you should do

  • Take OMEPRAZOLE-WGR exactly as your doctor has prescribed
  • If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking OMEPRAZOLE-WGR.
  • Tell any other doctors, dentists and pharmacists who treat you that you are taking this medicine.
  • If you become pregnant while taking OMEPRAZOLE-WGR, tell your doctor immediately.
  • Tell your doctor if your symptoms return. Although OMEPRAZOLE-WGR can heal ulcers successfully, it may not prevent them recurring at a later date.
  • Tell your doctor if you need to have any medical tests while you are taking OMEPRAZOLE-WGR. It may affect the results of some tests.

Things you should not do

  • Do not stop taking this medicine or change the dosage without checking with your doctor. If you stop taking it suddenly or change the dose, your condition may worsen or you may have unwanted side effects.
  • Do not take OMEPRAZOLE-WGR to treat any other complaints unless your doctor tells you to.
  • Do not give your medicine to anyone else, even if they have the same condition as you

Driving or using machines

Be careful before you drive or use any machines or tools until you know how OMEPRAZOLE-WGR affects you.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

  • Keep your tablets in a cool, dry place where the temperature stays below 25°C.
  • Keep your tablets in the blister pack, until it is time to take them. If you take the tablets out of the blister, they may not keep well.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
These side effects are usually mild:
  • constipation
  • diarrhoea
  • nausea or vomiting
  • wind
  • stomach pain
  • headache
  • dizziness
  • skin rash, itchy skin
  • dry or sore mouth
  • flatulence
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
These are serious side effects which may require medical attention. Serious side effects are rare.
  • muscle pain or weakness, joint pain
  • tingling or numbness of the hands or feet
  • changes in sleep patterns
  • mood changes, confusion or depression
  • blurred vision
  • increase in breast size (males)
  • fever
  • increased bruising
  • increased sweating
  • hair loss
  • tremor
  • pain or indigestion that occurs during treatment with OMEPRAZOLE-WGR.
  • vomiting blood or food
  • blood in your stool (a dark black stool can be an indicator of this)
  • low magnesium blood levels may cause decrease of potassium or calcium levels in blood
  • involuntary muscle contraction, disorientation, convulsions, dizziness or increased heart rate caused by decrease in magnesium which may occur if you have been taking OMEPRAZOLE-WGR for a period of 3 or more months.
  • needing to urinate more frequently, lower back pain, fatigue can be signs of inflammation in your kidney.
Tell your doctor immediately if you notice any of these serious side effects
These are very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are very rare:
  • skin reaction which may include rash, redness, blistering or peeling of the skin
  • ulcers, blisters or bleeding of the lips, eyes, mouth, nose and genitals
  • swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing
  • swelling of hands, feet or ankles
  • shortness of breath or difficulty in breathing
  • blood in the urine
  • signs of liver inflammation including yellowing of the skin or eyes, feeling generally unwell, nausea, vomiting, loss of appetite
  • skin reaction, especially in sun exposed areas, with joint pain
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

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

Occasionally, OMEPRAZOLE-WGR may be associated with changes in your liver or blood, which may require your doctor to do certain blood tests.

When taking OMEPRAZOLE-WGR, inflammation in your kidney may occur. Signs and symptoms may include decreased volume of urine or blood in your urine and/or hypersensitivity reactions such as fever, rash, and joint stiffness.

You should report such signs to the treating physician.

Some health problems may arise from the condition beingtreated itself, rather than the treatment. For this reason, contact your doctor immediately if you notice any of the following:

  • pain or indigestion which occurs during treatment with OMEPRAZOLE-WGR
  • vomiting blood or food
  • passing black or blood-stained motions. Tell your doctor if your reflux symptoms return after you stop taking OMEPRAZOLE-WGR.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What OMEPRAZOLE-WGR contains

Active ingredient
(main ingredient)		omeprazole
Other ingredients
(inactive ingredients)
  • lactose monohydrate
  • sodium starch glycollate
  • sodium stearate
  • sodium stearylfumarate
  • hypromellose acetate succinate
  • triethyl citrate
  • sodium lauryl sulfate
  • carnauba wax
  • purified talc
  • monoethanolamine
  • propylene glycol
  • hypromellose
  • titanium dioxide
  • iron oxide yellow
  • iron oxide red
Potential allergenssugars (as lactose)

Do not take this medicine if you are allergic to any of these ingredients.

What OMEPRAZOLE-WGR looks like

OMEPRAZOLE-WGR tablets are brown capsule-shaped tablets debossed with ‘20’ on one side.
Each bottle or blister contains 30 tablets.
AUST R 444390 (blisters); AUST R 444410 (bottles)

Who distributes OMEPRAZOLE-WGR

Sponsor

Medis Pharma Pty Ltd
Level 1, 37 Epping Road
Macquarie Park, NSW 2113
Australia

Distributor

Arrotex Pharmaceuticals
15-17 Chapel Street
Cremorne, VIC 3121
Australia

This leaflet was prepared in January 2025.

Published by MIMS May 2025

BRAND INFORMATION

Brand name

Omeprazole-WGR

Active ingredient

Omeprazole

Schedule

S4

 

Notes

Distributed by Arrotex Pharmaceuticals Pty Ltd

1 Name of Medicine

Omeprazole.

2 Qualitative and Quantitative Composition

Omeprazole-WGR enteric-coated tablets contain 20 mg of omeprazole.

Excipients with known effect.

Contains sugars as lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Omeprazole-WGR 20 mg enteric-coated tablets are brown capsule-shaped tablets debossed with "20" on one side.

4 Clinical Particulars

4.1 Therapeutic Indications

Gastro-oesophageal reflux disease (GORD).

Symptomatic GORD.

The relief of heartburn and other symptoms associated with GORD.

Erosive oesophagitis.

The treatment and prevention of relapse.

Peptic ulcers.

The treatment of duodenal and gastric ulcer.
Combination therapy for the treatment of peptic ulcer disease associated with H. pylori infection.
The treatment of gastric and duodenal ulcers and erosions associated with non-steroidal anti-inflammatory drugs.
The prevention of gastric and duodenal ulcers and erosions associated with non-steroidal anti-inflammatory drugs in patients assessed as being at high risk of gastroduodenal ulcer or complications of gastroduodenal ulcer.
Long-term prevention of relapse in gastric and duodenal ulceration, in patients proven to be H. pylori negative, or in whom eradication is inappropriate, e.g. the elderly or ineffective.

Zollinger-Ellison syndrome.

The treatment of Zollinger-Ellison syndrome.

4.2 Dose and Method of Administration

Omeprazole-WGR tablets must be swallowed whole (not broken, halved or chewed) with liquid. Omeprazole-WGR is only available as 20 mg strength. For 10 mg dosing, other brands of omeprazole available as the 10 mg strength should be used.

Adults.

Symptomatic gastro-oesophageal reflux disease (GORD). Recommended dose for symptom relief is omeprazole 10 to 20 mg once daily for a maximum of four weeks.
In most patients symptom relief is rapid. If symptom control has not been achieved after four weeks treatment with omeprazole 20 mg daily, further investigation is recommended.
Erosive oesophagitis. Recommended healing dosage is omeprazole 20 mg once daily for four to eight weeks.
In most patients, symptomatic relief is rapid and healing is usually complete within four weeks. For those patients not fully healed on endoscopic examination during initial treatment, endoscopic healing usually occurs during a further four weeks treatment period.
In patients with ulcerative reflux oesophagitis refractory to treatment, omeprazole 40 mg once daily usually produces healing within eight weeks.

Maintenance therapy.

It is recommended that, after healing, maintenance therapy be commenced, omeprazole 10 mg once daily. If needed, this dose should be increased to omeprazole 20 mg once daily.
Peptic ulcer disease associated with Helicobacter pylori infection. Patients whose gastric or duodenal ulceration is not associated with ingestion of non-steroidal anti-inflammatory drugs require treatment with antimicrobial agents in addition to antisecretory drugs whether on first presentation or on recurrence. Omeprazole administered at a dose of 40 mg once daily or 20 mg twice daily in association with the following combinations has been found to achieve eradication rates of approximately 90%:
amoxicillin 500 mg and metronidazole 400 mg both three times a day, for two weeks; or
amoxicillin 1 g and clarithromycin 500 mg both twice a day for one week; or
clarithromycin 250 mg and metronidazole 400 mg twice a day for one week.
Patients should be retreated if there is a return of symptoms and H. pylori infection. In this situation, possible resistance of the organism to the antimicrobial agents should be considered when deciding on the combination to be used.
To ensure healing in patients with active peptic ulcer disease, see further dosage recommendations for duodenal and gastric ulcer.
Duodenal ulcer. Recommended healing dosage is omeprazole 20 mg orally once daily for four to eight weeks.
In most patients, symptomatic relief is rapid and healing is usually complete within four weeks. For those patients not fully healed during initial treatment, healing usually occurs during a further four week treatment period.
In duodenal ulcer patients refractory to treatment, omeprazole 40 mg once daily usually produces healing within four to eight weeks.

Maintenance therapy.

For the long-term prevention of relapse in patients with duodenal ulcer who are proven to be H. pylori negative and whose ulceration had not been associated with non-steroidal anti-inflammatory drugs (NSAIDs), the recommended dose is omeprazole 10 to 20 mg daily.
For NSAID associated duodenal ulcers see NSAID associated gastric or duodenal ulcers or erosions.
Gastric ulcer. Recommended healing dosage is omeprazole 20 mg once daily for four to eight weeks.
In most patients, symptomatic relief is rapid and healing is usually complete within four weeks.
For those patients not fully healed during initial treatment, healing usually occurs during a further four weeks treatment period.
In gastric ulcer patients refractory to treatment, omeprazole 40 mg once daily usually produces healing within eight weeks.

Maintenance therapy.

For the long-term prevention of relapse in patients with gastric ulcer who are proven to be H. pylori negative and whose ulceration had not been associated with non-steroidal anti-inflammatory drugs (NSAIDs), the recommended dose is omeprazole 20 mg daily.
For non-steroidal anti-inflammatory drug (NSAID) associated duodenal ulcers see NSAID associated gastric or duodenal ulcers or erosions.
NSAID associated gastric or duodenal ulcers or erosions. In patients with or without continued NSAID treatment, the recommended dose is omeprazole 20 to 40 mg daily. Symptom resolution is rapid and healing occurs within four weeks in most patients. For those patients not fully healed after the initial course, healing usually occurs during a further four weeks treatment period. For the prevention of NSAID associated gastric or duodenal ulcers or erosions and dyspeptic symptoms, the recommended dose is omeprazole 20 mg once daily.
Zollinger-Ellison syndrome. Recommended initial dose is omeprazole 60 mg once daily.
The dosage should be adjusted individually and treatment continued for as long as is clinically indicated. More than 90% of patients with severe disease and inadequate response to other therapies have been effectively controlled on doses of 20 to 120 mg daily. When doses exceed 80 mg orally daily, the dose should be divided and given twice daily.

Use in children 1 year and older.

For children weighing > 20 kg the recommended dose is omeprazole 20 mg once daily for 2 to 8 weeks. If needed the dose may be increased to 40 mg.
For children weighing 10 to 20 kg the recommended dose is omeprazole 10 mg once daily for 2 to 8 weeks. If needed the dose may be increased to 20 mg. Omeprazole-WGR is only available as 20 mg strength. The tablets must not be broken, halved or chewed. For 10 mg dosing, other brands of omeprazole available as the 10 mg strength should be used.

Use in the elderly.

No dosage adjustment of omeprazole is necessary in the elderly.

Use in patients with 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 dose of 20 mg omeprazole daily and no adjustment to the normal dosage regime is required (see Section 4.4 Special Warnings and Precautions for Use).

Use in patients with renal impairment.

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

4.3 Contraindications

Hypersensitivity to omeprazole, substituted benzimidazoles or any other ingredients in the tablets.
Omeprazole, an inhibitor of CYP2C19 is contraindicated in patients taking cilostazol.

4.4 Special Warnings and Precautions for Use

Undiagnosed malignancy.

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

Concomitant therapy with clopidogrel.

Results from studies in healthy subjects have shown a pharmacokinetic/pharmacodynamic interaction between clopidogrel (300 mg loading dose/75 mg daily maintenance dose) and omeprazole (80 mg p.o. daily, i.e. four times the recommended dose) resulting in decreased exposure to the active metabolite of clopidogrel by an average of 46% and resulting in decreased maximum inhibition of (ADP induced) platelet aggregation by an average of 16%. Based on these data, concomitant use of omeprazole and clopidogrel should be avoided (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Acute interstitial nephritis.

Acute interstitial nephritis has been observed in patients taking proton pump inhibitors (PPIs) including omeprazole. Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to idiopathic hypersensitivity reaction. Discontinue omeprazole if acute interstitial nephritis develops.

Cyanocobalamin (vitamin B-12) deficiency.

Daily treatment with acid-suppressing medicines over a long period of time (e.g. longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B-12) caused by hypo- or achlorhydria.

Osteoporotic fractures.

Some published case controlled and observational studies suggest that proton-pump inhibitor therapy may be associated with an increased risk for osteoporosis-related fractures.
The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.
Patients at risk for developing osteoporosis or osteoporotic fractures are advised to have appropriate clinical monitoring in accordance with current clinical guidelines for these conditions.

Antimicrobial resistance.

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

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 of acid inhibition.

Decreased gastric acidity due to any means including proton pump inhibitors increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with acid-reducing drugs may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter and possibly also Clostridium difficile in hospitalised patients.

Subacute cutaneous lupus erythematosus.

Subacute cutaneous lupus erythematosus (SCLE) has been reported with the use of PPIs. 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. The occurrence of SCLE with previous PPI treatment may increase the risk of SCLE with other PPIs.

Hypomagnesaemia.

Hypomagnesaemia, symptomatic or asymptomatic, has been reported rarely in patients treated with PPIs. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesaemia require magnesium replacement and discontinuation of PPI.
For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesaemia (e.g. diuretics), healthcare professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically during PPI treatment.
Hypomagnesaemia may lead to hypocalcemia and/or hypokalaemia (see Section 4.8 Adverse Effects (Undesirable Effects)).

Renal impairment.

Acute tubulointerstitial nephritis (TIN) has been observed in patients taking omeprazole and may occur at any point during omeprazole therapy (see Section 4.8). Acute tubulointerstitial nephritis can progress to renal failure. Omeprazole should be discontinued in case of suspected TIN, and appropriate treatment should be promptly initiated.

Use in hepatic impairment.

Patients with impaired liver function show a markedly increased bioavailability, a reduced total plasma clearance, and up to a fourfold 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.

See Section 4.2 Dose and Method of Administration.

Paediatric use.

See Section 4.8 Adverse Effects (Undesirable Effects).

Effects on laboratory tests.

Chromogranin A (CgA) increases due to decreased gastric acidity. The increased CgA level may interfere with investigations for neuroendocrine tumours. Literature reports indicate that proton pump inhibitor treatment should be stopped 5 to 14 days before CgA measurement. Measurements should be repeated if levels have not normalised by this time.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Absorption.

Medicinal products with pH dependent absorption.

The decreased intragastric acidity during treatment with omeprazole 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, e.g. ketoconazole, itraconazole, erlotinib etc., may decrease and absorption of digoxin can increase during treatment with omeprazole. 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).
Co-administration of omeprazole in healthy subjects and in transplant patients receiving mycophenolate mofetil has been reported to reduce exposure to the active metabolite, mycophenolic acid. This is possibly due to a decrease in mycophenolate mofetil solubility at an increased gastric pH. The clinical relevance of reduced mycophenolic acid exposure on organ rejection has not been established in transplant patients receiving omeprazole and mycophenolate mofetil. Use omeprazole with caution in transplant patients receiving mycophenolate mofetil.

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.

Effects of omeprazole on other drugs.

Clopidogrel.

Results from studies in healthy subjects have shown a pharmacokinetic/pharmacodynamic (PK/PD) interaction between clopidogrel (300 mg loading dose/75 mg daily maintenance dose) and omeprazole (80 mg p.o. daily, i.e. four times the recommended dose) resulting in decreased exposure to the active metabolite of clopidogrel by an average of 46%, and resulting in decreased maximum inhibition of (ADP induced) platelet aggregation by an average of 16%. Based on these data, concomitant use of omeprazole and clopidogrel should be avoided.
When clopidogrel was given together with a fixed dose combination of esomeprazole 20 mg + ASA 81 mg compared to clopidogrel alone in a study in healthy subjects there was a decreased exposure by almost 40% of the active metabolite of clopidogrel. However, the maximum levels of inhibition of (ADP induced) platelet aggregation in these subjects were similar in the clopidogrel and the clopidogrel + the combined (esomeprazole + ASA) product groups.
There are both observational and clinical studies on the clinical implications of a PK/PD interaction (with proton pump inhibitors, including omeprazole) investigating the number of major cardiovascular events when clopidogrel and proton pump inhibitors are given concomitantly.

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-WGR tablets are co-prescribed.

Phenytoin.

Omeprazole 40 mg daily for seven days reduced plasma clearance of 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 epileptic patients, steady-state plasma levels of phenytoin were unchanged during omeprazole treatment.

Cilostazol.

Omeprazole 40 mg daily 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 proton pump inhibitors, 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.

Warfarin.

Concomitant administration of 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.
In patients receiving warfarin or other vitamin K antagonists, monitoring of INR is recommended and a reduction of the warfarin (other vitamin K antagonists) dose may be necessary.

Anti-viral drugs.

Concomitant administration with omeprazole and drugs such as atazanavir and nelfinavir is not recommended.
Omeprazole has been reported to interact with some anti-retroviral 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 anti-retroviral drug. Other possible interaction mechanisms are via CYP2C19. For some anti-retroviral drugs, such a atazanavir and nelfinavir, decreased serum levels have been reported when given together with omeprazole. For other anti-retroviral drugs, such as saquinavir, elevated serum levels have been reported. There are also some anti-retroviral drugs of which unchanged levels have been reported when given with omeprazole.

Tacrolimus.

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

Potential interactions that have been excluded.

Results from a range of in vitro 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 (ciclosporin, lignocaine, quinidine and estradiol).

Effects of other drugs on omeprazole.

Drugs 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 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.

Voriconazole.

Concomitant administration of omeprazole and voriconazole, a CYP2C19 and CYP3A4 inhibitor, resulted in more than doubling of the omeprazole exposure.

Clarithromycin.

Plasma concentrations of omeprazole are increased during concomitant administration.

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 sevenfold clinical exposure was associated with embryofoetal toxicity.
(Category B3)

Australian categorisation definition of Category B3.

Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

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). Embryofoetal 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 (sevenfold 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.

4.8 Adverse Effects (Undesirable Effects)

Omeprazole tablets are well tolerated. Most adverse reactions have been mild and transient and there has been no consistent relationship with treatment.
Adverse reactions within each body system are listed in descending order of frequency (very common: greater than or equal to 10%; common: greater than or equal to 1% and < 10%; uncommon: greater than or equal to 0.1% and < 1%; rare: greater than or equal to 0.01% and < 0.1%; very rare: < 0.01%).
These include the following.

Immune system disorders.

Rare: hypersensitivity reactions e.g. fever, angioedema and anaphylactic reaction/shock.

Metabolism and nutrition disorders.

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

Psychiatric disorders.

Uncommon: insomnia.
Rare: agitation, aggression, reversible mental confusion, depression, hallucinations.

Gastrointestinal disorders.

Common: diarrhoea, constipation, abdominal pain, nausea/vomiting, flatulence.
Rare: stomatitis, gastrointestinal candidiasis, microscopic colitis, and dry mouth.
Very rare: dyspepsia, haemorrhagic necrotic gastritis (reported in children).
Frequency not known: Withdrawal of long-term PPI therapy can lead to aggravation of acid-related symptoms and may result in rebound acid hypersecretion.

Nervous system disorders.

Common: headache.
Uncommon: dizziness, paraesthesia, somnolence.
Rare: taste disturbance.

Eye disorders.

Rare: blurred vision.

Ear and labyrinth disorders.

Uncommon: vertigo.

Respiratory, thoracic, and mediastinal disorders.

Rare: bronchospasm.
Very rare: dyspnoea.

Hepatic 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, urticaria, pruritus, dermatitis.
Rare: photosensitivity, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), alopecia, acute generalised exanthematous pustulosis (AGEP), drug rash with eosinophilia and systemic symptoms (DRESS).
Not known: Subacute cutaneous lupus erythematosus (SCLE).

Renal and urinary disorders.

Rare: tubulointerstitial nephritis (with possible progression to renal failure).
Very rare: impaired renal function, including nephrosis.

General disorders and administration site conditions.

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

Reproductive system and breast disorders.

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

Blood and lymphatic disorders.

Rare: leucopenia, thrombocytopenia, agranulocytosis and pancytopenia.

Musculoskeletal, connective tissue and bone disorders.

Rare: arthralgia, muscular weakness and myalgia.

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

Symptoms.

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 omeprazole 2,400 mg (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. The rate of elimination was unchanged (first-order kinetics) with increased doses and no specific treatment has been needed.

Treatment.

In suspected cases of overdosage treatment should be supportive and symptomatic.
For information on the management of overdose, contact the Poisons 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 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 activities return to approximately 50% of maximum after 24 hours and gradually return to normal over three to five days.

Peptic ulcer disease associated with Helicobacter pylori.

Helicobacter pylori (H. pylori) is associated with duodenal and gastric ulcer disease in about 95 and 70% of patients, respectively. H. pylori is the major factor in the development of gastritis and ulcers in such patients. Recent evidence also suggests a causative link between H. pylori and gastric carcinoma. An attempt to eradicate H. pylori is appropriate therapy in most patients with duodenal and gastric ulcer where the latter is not caused by non-steroidal anti-inflammatory drug (NSAID) ingestion (see Section 4.2 Dose and Method of Administration).
In vitro testing has shown that omeprazole has an MIC90 (minimum inhibitory concentration) of 25 microgram/mL against H. pylori. However, in vivo it only suppresses the organism without eradicating it. The combination of omeprazole and antimicrobial agents results in eradication of the organism in vivo, despite the fact that antimicrobial agents administered singly have also proved ineffective in eradicating H. pylori. The mechanism of the synergy between omeprazole and antimicrobial agents in eradicating H. pylori is not completely understood. Optimal eradication rates are achieved when omeprazole is combined with two antimicrobial agents.
Eradication of H. pylori is associated with reduced peptic ulcer recurrence.

Other effects related to acid inhibition.

During long term treatment gastric glandular cysts have been reported in a somewhat increased frequency. These changes are benign and appear to be reversible. 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.

Clinical trials.

Gastro-oesophageal reflux disease (GORD).

Symptomatic GORD.

Randomised controlled clinical trials (n = 1,710) were evaluated to assess the efficacy of omeprazole in the complete relief of heartburn in adult patients with symptomatic GORD after four weeks treatment comparing omeprazole 10 mg and 20 mg once daily with control groups of ranitidine 150 mg twice daily or placebo. The percentage of patients with complete relief of heartburn after four weeks is presented in Table 1:

Erosive oesophagitis.

At the time of registration, seven randomised controlled clinical trials (n = 1,674) were evaluated to assess the efficacy of omeprazole in the prevention of relapse in patients with healed reflux oesophagitis. Omeprazole 10 mg and 20 mg once daily maintained endoscopic remission rates which substantially exceeded ranitidine 150 mg twice daily or placebo at six months. The difference in remission rates between omeprazole 10 mg and 20 mg favoured 20 mg. Three studies recorded remission rates over 12 months and an additional study continued for 18 months.
In a meta-analysis of five of the clinical trials (n = 1,154), 72 and 82% of patients remained in remission at six months on omeprazole 10 mg and 20 mg once daily, respectively. In a separate large study (n = 327), the remission rate following omeprazole 10 mg once daily for 18 months was 60%.
In two of the studies, patients who relapsed in the first three months of maintenance treatment were then healed and treated with a maintenance dose of omeprazole 20 mg. The difference in the total remission rate over six or twelve months, while small, suggests that it may be more difficult or take longer to obtain subsequent healing and control if 10 mg rather than 20 mg had been used for initial maintenance therapy.
Gastric safety data are available from seven controlled clinical trials of up to two years duration (irrespective of indication). A full analysis of these trials was undertaken as a consequence of histological changes observed in animals (see Section 4.4 Special Warnings and Precautions for Use). This involved a total of 1,128 patients with an evaluable series of biopsies; 843 patients treated continuously with omeprazole for six to twelve months, 77 patients completing 18 months, and 208 patients completing two years of continuous omeprazole treatment. Additionally, in open studies at least 109 patients were assessed by annual biopsy during continuous treatment for four years, and in this continuing study, biopsies are available for at least 14 patients treated for up to eight years. No instances of dysplasia or carcinoids of the gastric ECL cells have been reported in these studies. An association between focal hyperplasia and chronic gastritis with atrophy was found during long-term therapy. However, this finding is also observed in patients with untreated gastric ulcer disease with normal gastrin levels and is thus not a treatment related effect.

Use in children.

In a trial in 65 children aged 0.5 to 17 years with erosive reflux oesophagitis, an oral omeprazole dose of 2.1 mg/kg/day was required to achieve endoscopic healing in 80% of the 57 patients who completed the study. The duration of treatment was 12 to 60 weeks. Reasons for discontinuing treatment were difficulty in administering the drug or inappropriate inclusion in the study.
In 13 children aged 1 to 17 years, oral omeprazole 0.5 to 0.6 mg/kg/day for eight weeks achieved endoscopic healing in two children with giant gastric ulcer, six children with duodenal ulcer and four out of five children with oesophagitis.
There are no data on the use of omeprazole in children with less severe gastro-oesophageal reflux disease.

5.2 Pharmacokinetic Properties

Absorption.

Omeprazole is acid labile and is administered orally as enteric-coated tablets. The enteric-coating film, protecting the omeprazole, dissolves at a pH above 5. Hence omeprazole is not released until the tablet is dissolved in the duodenum.
Absorption is rapid with peak plasma levels of omeprazole occurring within four hours and is usually complete within three to six hours. The systemic bioavailability of omeprazole from a single oral dose of omeprazole tablets is approximately 35%. After repeated once daily administration, the bioavailability increases to about 60%.
Food increased Tmax by about 2.5 hours and Cmax by about 20%, but had no effect on AUC. However, these differences are not clinically significant.

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 hydroxy-omeprazole. These metabolites have no significant effect on acid secretion. The average half-life of the terminal phase of the plasma concentration time curve following intravenous 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 hydroxy omeprazole and the corresponding carboxylic acid.

Pharmacokinetics in children.

Available data from children (greater than or equal to 1 year) suggests that the pharmacokinetics, within the recommended dosages, are similar to those reported in adults.

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 these 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 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 whom 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-WGR enteric-coated tablets contain the following excipients: lactose monohydrate, sodium starch glycollate, sodium stearate, sodium stearylfumarate, hypromellose acetate succinate, triethyl citrate, sodium lauryl sulfate, carnauba wax, purified talc, monoethanolamine, propylene glycol, hypromellose, titanium dioxide, iron oxide yellow and iron oxide red.

6.2 Incompatibilities

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

Store below 25°C.

6.5 Nature and Contents of Container

Omeprazole-WGR 20 mg enteric-coated tablets are brown capsule-shaped tablets debossed with "20" on one side. They are available in bottles (HDPE with child resistant closure)* or blister packs (Al/Al) of 30 tablets.
*Currently not marketed in Australia.

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

A white or almost white powder, very slightly soluble in water, soluble in methylene chloride, sparingly soluble in alcohol and in methanol. It dissolves in dilute solutions of alkali hydroxides.

Chemical structure.


5-methoxy-2-[(RS)-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-sulphinyl]-1H-benzimidazole.
C17H19N3O3S.
MW: 345.4.

CAS number.

73590-58-6.

7 Medicine Schedule (Poisons Standard)

S4 - Schedule 4.

Summary Table of Changes