Consumer medicine information

Losec Tablets

Omeprazole

BRAND INFORMATION

Brand name

Losec Tablets

Active ingredient

Omeprazole

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Losec Tablets.

SUMMARY CMI

LOSEC®

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 taking LOSEC®?

LOSEC® contains the active ingredient omeprazole (as magnesium). LOSEC® is used to treat: the symptoms of reflux oesophagitis or reflux disease; 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 LOSEC®? in the full CMI.

2. What should I know before I take LOSEC®?

Do not use if you have ever had an allergic reaction to omeprazole magnesium 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 LOSEC®? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with LOSEC® 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 take LOSEC®?

  • Take one LOSEC® tablet each day, unless your doctor has told you otherwise.
  • Swallow LOSEC® whole with a glass of water. Do not crush or chew the tablets.
  • If you have difficulty swallowing the tablets, follow the instructions in Section 4. How do I use LOSEC®?

More instructions can be found in Section 4. How do I use LOSEC®? in the full CMI.

5. What should I know while using LOSEC®?

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

For more information, see Section 5. What should I know while using LOSEC®? in the full CMI.

6. Are there any side effects?

Mild side effects include: constipation, nausea or vomiting, diarrhoea, wind, stomach pain, headache, dizziness, skin rash, itchy skin, dry or sore mouth.

Serious side effects (Call your doctor straight away, or go straight to the Emergency Department) include: swelling of the face, lips, mouth, tongue or throat, shortness of breath or difficulty in breathing, skin reaction (which may include rash, itching, redness, blistering or peeling of the skin) especially in sun-exposed areas with joint pain, ulcers, blisters or bleeding of the lips, eyes, mouth, nose and genitals, blood in the urine, swelling of hands, feet or ankles, yellowing of the skin or eyes, feeling generally unwell, nausea, vomiting, loss of appetite.

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

LOSEC®

Active ingredient(s): omeprazole magnesium


Consumer Medicine Information (CMI)

This leaflet provides important information about using LOSEC®. 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 LOSEC®.

Where to find information in this leaflet:

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

1. Why am I taking LOSEC®?

LOSEC® contains the active ingredient omeprazole (as magnesium). LOSEC® is a type of medicine called a proton-pump inhibitor. It works by decreasing 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.

Reflux Oesophagitis

LOSEC® is used to treat the symptoms of reflux oesophagitis or reflux disease.

This can be caused by "washing back" (reflux) of food and acid from the stomach into the food pipe (oesophagus).

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

LOSEC® is also taken to help stop reflux oesophagitis coming back or relapsing.

Peptic Ulcers

LOSEC® is used to treat 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 from the stomach.

These ulcers can be caused by too much acid being made in the stomach.

LOSEC® is also used to help stop gastric or duodenal ulcers coming back.

Peptic Ulcers Associated with Helicobacter pylori Infection

LOSEC® is used to treat peptic ulcers associated with helicobacter pylori infection.

Most people who have a peptic ulcer also have a bacterium called Helicobacter pylori in their stomach.

When LOSEC® is taken with antibiotics, they work to kill the bacterium and let your ulcer heal. You may need further treatment with antibiotics.

Peptic Ulcers Associated with Non-steroidal Anti-Inflammatory Drugs (NSAIDs)

LOSEC® is used to treat peptic ulcers associated with non-steroidal anti-inflammatory drugs (NSAIDs).

Some peptic ulcers are caused by taking medicines called non-steroidal anti-inflammatory drugs (NSAIDs), a type of medicine used to treat pain or inflammation.

LOSEC® is also used to heal and prevent ulcers associated with NSAIDs.

Zollinger-Ellison Syndrome

LOSEC® is also used to treat a rare condition called Zollinger-Ellison syndrome.

This syndrome is where the stomach produces large amounts of acid, much more than in ulcers or reflux disease.

There is no evidence that LOSEC® is addictive.

2. What should I know before I take LOSEC®?

Warnings

Do not take LOSEC® if:

  • you are allergic to omeprazole, or any of the ingredients listed at the end of this leaflet.
  • you are allergic to any medicine containing a proton pump inhibitor.
  • Always check the ingredients to make sure you can use this medicine.
    Some of the symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin.
  • you are also taking cilostazol.
    Please check with your doctor or pharmacist if you are taking cilostazol. This medicine will be affected by LOSEC®.
  • the use by (expiry) date printed on the pack or if the packaging is torn or shows signs of tampering.
    If it has expired or is damaged, return it to your pharmacist for disposal.

Check with your doctor if you have:

  • allergies to any other medicines, foods, dyes or preservatives.
  • take any medicines for any other condition.
  • any problems with your liver.
  • any other medical conditions.
  • been diagnosed with osteoporosis.
  • ever had a skin reaction after treatment with a medicine similar to LOSEC® 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 LOSEC® 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 LOSEC® 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 LOSEC® 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 LOSEC® if you are taking the following medicine:

  • cilostazol - a medicine used to treat intermittent claudication.

Some medicines may interfere with LOSEC® and affect how it works.

  • phenytoin - a medicine used to treat epilepsy or fits.
  • warfarin and clopidogrel - medicines 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, voriconazole - medicines used to treat fungal infection.
  • clarithromycin or rifampicin - medicines used to treat infections.
  • atazanavir and nelfinavir - medicines used to treat viral infections such as HIV.
  • tacrolimus and mycophenolate mofetil - medicines used to assist in organ transplants.
  • methotrexate - a medicine used to treat arthritis and some types of cancer.
  • erlotinib or related medicines used to treat cancer.

These medicines may be affected by LOSEC® or may affect how well it works. You may need different amounts of your medicine 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 these things, tell them before you take LOSEC®.

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

4. How do I take LOSEC®?

How much to take

  • Take one LOSEC® tablet each day, unless your doctor has told you otherwise.
  • Adults: The dose of LOSEC® is usually 20 mg a day.
    The dose may vary from 10 mg to 40 mg a day depending on what condition you are being treated for and how severe it is.
  • Children (1 year or older): The dose of LOSEC® is 10 mg a day for children 10 to 20 kg. This dose may be increased to 20 mg if required. For children more than 20 kg the dose is 20 mg a day. This dose may be increased to 40 mg if required.
  • Follow the instructions provided and use LOSEC® until your doctor tells you to stop.

When to take LOSEC®

  • Take LOSEC® at about the same time each day.
  • Keeping a regular time for taking LOSEC® will help to remind you to take it.
  • LOSEC® can be taken with food or on an empty stomach.

How to take LOSEC®

  • Swallow LOSEC® whole with a glass of water. Do not crush or chew the tablets.
  • If the tablets are chewed or crushed, they will not work properly.
  • Keep taking LOSEC® for as long as your doctor recommends.
    In most patients, LOSEC® relieves symptoms rapidly and healing is usually complete within 4 weeks. Continue taking LOSEC® for as long as your doctor tells you to.

If you have difficulty swallowing the tablets:

  1. Place the tablet in half a glass of non-carbonated water or fruit juice. Mineral water, carbonated fruit juices, or other liquids are not suitable.
  2. Gently mix the tablet and liquid by stirring, taking care not to crush the tablet.
  3. Stir until the tablet disperses into little pellets.
  4. Drink the liquid with the pellets immediately, or within 30 minutes. Do not chew the pellets.
  5. Rinse the glass with half a glass of water and drink.

If you forget to use LOSEC®

LOSEC® should be used regularly at the same time each day. If you miss your dose at the usual time, take it as soon as you remember, and then go back to taking it 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 LOSEC®

If you think that you have used too much LOSEC®, 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.

5. What should I know while using LOSEC®?

Things you should do

Take LOSEC® exactly as your doctor has prescribed.

If you are about to start any new medicine, remind your doctor and pharmacist that you are taking LOSEC®.

Tell all doctors, dentists and pharmacists who are treating you that you are taking LOSEC®.

Tell your doctor if you become pregnant while you are taking LOSEC®.

Tell your doctor if your symptoms return.

Although LOSEC® can heal ulcers successfully, it may not prevent them recurring at a later date.

If you need to have any medical tests while you are taking LOSEC®, tell your doctor.

It may affect the results of some tests.

Remind any doctor, dentist or pharmacist you visit that you are using LOSEC®.

Things you should not do

  • Do not take LOSEC® 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.
  • Do not stop taking your 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.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how LOSEC® affects you.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

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

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 windowsills.

Keep it where young children cannot reach it.

When to discard your medicine

If your doctor tells you to stop taking LOSEC® or the tablets have passed their expiry date, ask your pharmacist what to do with any tablets you have left over.

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
  • nausea or vomiting
  • diarrhoea
  • wind
  • stomach pain
  • headache
  • dizziness
  • skin rash, itchy skin
  • dry or sore mouth
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 that may require medical attention. Serious side effects are rare.

  • muscle pain or weakness, joint pain
  • "pins and needles"
  • 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 LOSEC®
  • you begin to vomit blood or food
  • you pass black (blood-stained) motions
Tell your doctor immediately if you notice any of theses serious side effects.

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

  • swelling of the 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 the urine
  • swelling of hands, feet or ankles
  • 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, LOSEC® may be associated with changes in your liver or blood, which may require your doctor to do certain blood tests.

Other problems are more likely to arise from the ulcer itself rather than the treatment.

Tell your doctor if your reflux symptoms return after you stop taking LOSEC®.

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 LOSEC® contains

Active ingredient
(main ingredient)
Omeprazole magnesium
Other ingredients
(inactive ingredients)
Glyceryl monostearate
Hyprolose
Hypromellose
Magnesium stearate
Methacrylic acid copolymer
Microcrystalline cellulose
Synthetic paraffin
Macrogol 6000
Polysorbate 80
Crospovidone
Sodium stearylfumarate
Purified talc
Titanium dioxide
Triethyl citrate
Sodium hydroxide
Sugar spheres (maize starch and sucrose)
Iron oxide red (CI77491)
Iron oxide yellow (CI77492)

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

LOSEC® tablets do not contain gluten.

What LOSEC® looks like

LOSEC® 10 mg tablets are light pink, oblong shaped, marked with 10 mg on one side and a logo on the other side.

LOSEC® 20 mg tablets are pink, oblong shaped, marked with 20 mg on one side and a logo on the other side.

Australian Registration Numbers:

LOSEC® 10 mg (blister pack) - AUST R 63414

LOSEC® 20 mg (blister pack) - AUST R 63416

LOSEC® 40 mg (blister pack) - AUST R 63418*

*non-marketed

Who distributes LOSEC®

Pharmaco (Australia) Ltd
Suite 1A, Level 2, 802 Pacific Highway
Gordon NSW 2072
Phone: 1800 201 564

Under license of CHEPLAPHARM Arzneimittel GmbH, Germany.

This leaflet was prepared in November 2021.

Published by MIMS February 2022

BRAND INFORMATION

Brand name

Losec Tablets

Active ingredient

Omeprazole

Schedule

S4

 

1 Name of Medicine

Omeprazole magnesium.

2 Qualitative and Quantitative Composition

The active ingredient in Losec Tablets is omeprazole magnesium, a substituted benzimidazole. Losec is available in 10 mg, 20 mg and 40 mg tablets containing omeprazole magnesium 10.3 mg, 20.6 mg and 41.3 mg, respectively, as the active ingredient.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Losec Tablets 10 mg are a light pink, oblong, biconvex, film-coated tablet engraved with the Losec logo on one side and 10 mg on the other. Each tablet contains omeprazole magnesium 10.3 mg as enteric-coated pellets.
Losec Tablets 20 mg are a pink, oblong, biconvex, film-coated tablet engraved with the Losec logo on one side and 20 mg on the other. Each tablet contains omeprazole magnesium 20.6 mg as enteric-coated pellets.
Losec Tablets 40 mg# are a red-brown, oblong, biconvex, film-coated tablet engraved with the Losec logo on one side and 40 mg and a score on the other. Each tablet contains omeprazole magnesium 41.3 mg as the enteric-coated pellets.
#Not marketed.

4 Clinical Particulars

4.1 Therapeutic Indications

Losec Tablets are indicated for:

Gastro-oesophageal reflux disease (GORD).

1. Symptomatic GORD.

The relief of heartburn and other symptoms associated with GORD.

2. Erosive oesophagitis.

The treatment and prevention of relapse.

Peptic ulcers.

1. The treatment of duodenal and gastric ulcer.
2. Combination therapy for the treatment of peptic ulcer disease associated with Helicobacter pylori infection.
3. The treatment of gastric and duodenal ulcers and erosions associated with non-steroidal anti-inflammatory drugs.
4. 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.
5. Long-term prevention of relapse in gastric and duodenal ulceration, in patients proven to be Helicobacter 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

Losec Tablets should be swallowed whole (not broken or chewed) with liquid.
If required, the tablets can also be dispersed in half a glass of non-carbonated water (mineral water is not suitable) or non-carbonated fruit juices. Stir until the tablets disintegrate and drink the liquid with the pellets immediately or within 30 minutes. Rinse the glass with half a glass of water and drink. The pellets must not be chewed or crushed.

Symptomatic GORD.

Recommended dose for symptom relief: Losec Tablets 10 mg to 20 mg once daily for a maximum of 4 weeks.
In most patients symptom relief is rapid. If symptom control has not been achieved after 4 weeks treatment with Losec Tablets 20 mg daily, further investigation is recommended.

Erosive oesophagitis.

Recommended healing dosage: Losec Tablets 20 mg once daily for 4 to 8 weeks.
In most patients, symptomatic relief is rapid and healing is usually complete within 4 weeks. For those patients not fully healed on endoscopic examination during initial treatment, endoscopic healing usually occurs during a further 4 weeks treatment period.
In patients with ulcerative reflux oesophagitis refractory to treatment, Losec Tablets 40 mg once daily usually produces healing within 8 weeks.

Maintenance therapy.

It is recommended that, after healing, maintenance therapy be commenced, Losec Tablets 10 mg once daily. If needed, this dose should be increased to Losec Tablets 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%:
amoxycillin 500 mg and metronidazole 400 mg both three times a day, for two weeks; or
amoxycillin 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: Losec Tablets 20 mg orally once daily for 4 to 8 weeks.
In most patients, symptomatic relief is rapid and healing is usually complete within 4 weeks. For those patients not fully healed during initial treatment, healing usually occurs during a further 4 weeks treatment period.
In duodenal ulcer patients refractory to treatment, Losec Tablets 40 mg once daily usually produces healing within 4 to 8 weeks.

Maintenance therapy.

For the long-term prevention of relapse in patients with duodenal ulcer who are proven to be Helicobacter pylori negative and whose ulceration had not been associated with non-steroidal anti-inflammatory drugs (NSAIDs), the recommended dose is Losec Tablets 10 mg to 20 mg daily.
For NSAID-associated duodenal ulcers see NSAID-associated gastric or duodenal ulcers or erosions.

Gastric ulcer.

Recommended healing dosage: Losec Tablets 20 mg once daily for 4 to 8 weeks.
In most patients, symptomatic relief is rapid and healing is usually complete within 4 weeks.
For those patients not fully healed during initial treatment, healing usually occurs during a further 4 weeks treatment period.
In gastric ulcer patients refractory to treatment, Losec Tablets 40 mg once daily usually produces healing within 8 weeks.

Maintenance therapy.

For the long-term prevention of relapse in patients with gastric ulcer who are proven to be Helicobacter pylori negative and whose ulceration had not been associated with non-steroidal anti-inflammatory drugs (NSAIDs), the recommended dose is Losec Tablets 20 mg daily.
For 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 Losec Tablets 20 mg to 40 mg daily. Symptom resolution is rapid and healing occurs within 4 weeks in most patients. For those patients not fully healed after the initial course, healing usually occurs during a further 4 weeks treatment period.
For the prevention of NSAID-associated gastric or duodenal ulcers or erosions and dyspeptic symptoms, the recommended dose is Losec Tablets 20 mg once daily.

Zollinger-Ellison syndrome.

Recommended initial dose: Losec Tablets 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 20-120 mg daily. When doses exceed 80 mg orally daily, the dose should be divided and given twice daily.

Use in children.

For use in children one year and older the recommended dose is:

Weight 10-20 kg.

Dose: Losec Tablets 10 mg once daily for 2 to 8 weeks.

Weight > 20 kg.

Dose: Losec Tablets 20 mg once daily for 2 to 8 weeks.
If needed the dose may be increased to 20 mg and 40 mg respectively.
The tablet may be dispersed in yoghurt or orange juice to assist with administration.

Elderly.

No dosage adjustment of Losec Tablets is necessary in the elderly.

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).

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 magnesium, substituted benzimidazoles or any other ingredients.
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, 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.

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 B12) 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 B12) 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 affect on eradication regimens. The clinical impact of this resistance on H. pylori has not been comprehensively studied.

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, in hospitalised patients, possibly also Clostridium difficile.

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 Losec. The occurrence of SCLE with previous PPI treatment may increase the risk of SCLE with other PPIs.

Special patient populations.

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 20 mg omeprazole 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 4.2 Dose and Method of Administration; Section 5.1 Pharmacodynamic Properties, Clinical trials.

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.

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.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Omeprazole is mainly metabolised via the hepatic cytochrome P-450 system (CYP2C19) and may be expected to interact with the metabolism of other drugs metabolised by this enzyme.

Effects of omeprazole on other drugs.

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 Losec Tablets are co-prescribed.

Phenytoin.

Omeprazole 40 mg daily for 7 days reduced plasma clearance of IV phenytoin by 15-20% 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.

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 (or other vitamin K antagonist) dose may be necessary.

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.

Antiretroviral drugs.

Concomitant administration with omeprazole and drugs such as atazanavir and nelfinavir is not recommended.
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. 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.

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.

Tacrolimus.

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

Medicinal products with pH dependent 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 (e.g. ketoconazole, itraconazole, erlotinib etc) may decrease and the absorption of drugs such as 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.

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.

Clarithromycin.

Plasma concentrations of omeprazole are increased during concomitant administration.

Voriconazole.

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

Potential interactions that have been excluded.

Results from a range of in vivo interaction studies with omeprazole versus other drugs indicate that omeprazole 20-40 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).

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 7-fold clinical exposure was associated with embryofoetal toxicity.
(Category B3)
Results from three prospective epidemiological studies indicate that whilst 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 (7-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 nursing mothers.

4.7 Effects on Ability to Drive and Use Machines

No effects have been observed.

4.8 Adverse Effects (Undesirable Effects)

Losec 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: ≥ 10%; common: ≥ 1% and < 10%; uncommon: ≥ 0.1% and < 1%; rare ≥ 0.01% and < 0.1%; very rare: < 0.01%). These include the following:

Blood and lymphatic disorders.

Rare: leukopenia, thrombocytopenia, agranulocytosis, pancytopenia.

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); severe hypomagnesaemia may result in hypocalcaemia.
Hypomagnesaemia may also result in hypokalaemia.

Psychiatric disorders.

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

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.

Gastrointestinal disorders.

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

Hepatobiliary disorders.

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

Skin and subcutaneous tissue disorders.

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

Musculoskeletal, connective tissue and bone disorders.

Rare: arthralgia, myalgia, muscular weakness.

Renal and urinary disorders.

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

Reproductive system and breast disorders.

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

General disorders and administration site conditions.

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

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 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 2400 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. The rate of elimination was unchanged (first-order kinetics) with increased doses and no specific treatment has been needed. In suspected cases of overdosage treatment should be supportive and symptomatic.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Losec is a proton pump inhibitor. 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 2 hours. With repeated once daily dosing the maximum effect is usually achieved within 4 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 3 to 5 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 NSAID ingestion (see Section 4.2 Dose and Method of Administration).
In vitro testing has shown that omeprazole has an MIC90 of 25 microgram/mL against H. pylori. However, in vivo it only suppresses the organism without eradicating it. The combination of omeprazole and antimicrobial agent 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.
In some patients, fasting serum gastrin levels have been noted to rise two to four-fold 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 = 1710) 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 % patients with complete relief of heartburn after 4 weeks is presented in Table 1.

Erosive oesophagitis.

At the time of registration, seven randomised controlled clinical trials (n = 1674) 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 bd or placebo at 6 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 5 of the clinical trials (n = 1154), 72% and 82% of patients remained in remission at 6 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 20 mg omeprazole. The difference in the total remission rate over 6 or 12 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 7 controlled clinical trials of up to 2 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 1128 patients with an evaluable series of biopsies; 843 patients treated continuously with omeprazole for 6-12 months, 77 patients completing 18 months, and 208 patients completing 2 years of continuous omeprazole treatment. Additionally, in open studies at least 109 patients were assessed by annual biopsy during continuous treatment for 4 years, and in this continuing study, biopsies are available for at least 14 patients treated for up to 8 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 0.5-17 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 12-60 weeks. Reasons for discontinuing treatment were difficulty in administering the drug or inappropriate inclusion in the study.
In 13 children aged 1-17 years, oral omeprazole 0.5-0.6 mg/kg/day for 8 weeks achieved endoscopic healing in 2 children with giant gastric ulcer, 6 children with duodenal ulcer and 4 out of 5 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 magnesium is acid labile and is administered orally as enteric coated granules in tablets. The enteric coating film, protecting the omeprazole magnesium, dissolves at a pH above 5.5. Hence omeprazole magnesium is not released until the pellets are emptied into the duodenum.
Once omeprazole magnesium dissolves in this near neutral environment, the omeprazole ion transforms to its neutral form. The same form of omeprazole is available for absorption regardless of it being administered as the free form, omeprazole, or the salt, omeprazole magnesium.
Absorption is rapid with peak plasma levels of omeprazole occurring within 4 hours and is usually complete within 3-6 hours. The systemic bioavailability of omeprazole from a single oral dose of Losec Tablets is approximately 35%. After repeated once daily administration, the bioavailability increases to about 60%. Concomitant intake of food has no influence on oral bioavailability but may reduce the rate of absorption of omeprazole.

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. The major part of its metabolism is dependent on the polymorphic CYP2C19. This CYP is responsible for the formation of hydroxyomeprazole, one of the major metabolites in plasma, and to a lesser extent, for the formation of 5-O-desmethyl omeprazole. The remaining part is mainly dependent on another specific isoform, CYP3A4, responsible for the formation of omeprazole sulphone.
Identified metabolites in plasma are the sulphone, the sulphide 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 IV administration of omeprazole is approximately 40 minutes; the total plasma clearance is 0.3 to 0.6 L/min. There is no change in half-life during repeated dosing.
The parameters below reflect mainly the pharmacokinetics in individuals with a functional CYP2C19 enzyme, extensive metabolisers.
Total plasma clearance is about 30-40 L/h after a single dose. The plasma elimination half-life of omeprazole is usually shorter than one hour both after single and repeated once daily dosing. The AUC of omeprazole increases with repeated administration. This increase is dose dependent and results in a non-linear dose-AUC relationship after repeated administration. This time and dose dependency is due to a decrease of first pass metabolism and systemic clearance probably caused by an inhibition of the CYP2C19 enzyme by omeprazole and/or its metabolites (e.g. the sulphone). Omeprazole is completely eliminated from plasma between doses with no tendency for accumulation during once-daily administration.

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 (≥ 1 year) suggest that the pharmacokinetics, within the recommended dosages, is similar to that 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 were markedly higher in female rats.
The same effects were seen in an additional 2-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:

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

Losec tablets contain the following inactive ingredients: glyceryl monostearate, hyprolose, hypromellose, magnesium stearate, methacrylic acid copolymer, microcrystalline cellulose, synthetic paraffin, macrogol 6000, polysorbate 80, crospovidone, sodium stearylfumarate, purified talc, titanium dioxide, triethyl citrate, sodium hydroxide and sugar spheres (maize starch and sucrose). The tablet is coloured with iron oxide red CI77491 and/or iron oxide yellow CI77492.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

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

Losec is provided in blister packs containing 30 tablets. The tablets should be dispensed and stored in the original container.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

The chemical name is di-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl]sulfinyl]-1H-benzimidazole magnesium. Omeprazole magnesium is a crystalline substance which is freely soluble in methanol and slightly soluble in water.
The chemical structure of omeprazole magnesium is:

CAS number.

95382-33-5.

Molecular formula.

C34H36N6O6S2Mg.

Molecular weight.

713.1.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes