Consumer medicine information

Omeprazole ADVZ

Omeprazole

BRAND INFORMATION

Brand name

Omeprazole ADVZ

Active ingredient

Omeprazole

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Omeprazole ADVZ.

SUMMARY CMI

Omeprazole ADVZ

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 ADVZ?

Omeprazole ADVZ contains the active ingredient omeprazole. Omeprazole ADVZ is used to treat the following conditions:

  • Reflux oesophagitis
  • Peptic ulcers
  • Peptic ulcers associated with Helicobacter pylori infection
  • Peptic ulcers associated with Non-steroidal Anti-Inflammatory Drugs (NSAIDs)
  • Children over 1 month of age: Reflux oesophagitis, symptoms of gastro-oesophageal reflux disease (GORD).

For more information, see Section 1. Why am I using Omeprazole ADVZ? in the full CMI.

2. What should I know before I use Omeprazole ADVZ?

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

3. What if I am taking other medicines?

Some medicines may interfere with Omeprazole ADVZ 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 ADVZ?

  • Take as much as advised to you by your doctor.
  • For doses of ≤ 15 mg, the 2 mg/mL strength is recommended. For doses of 20 mg or 40 mg, the 4 mg/mL strength is suitable.
  • Take on an empty stomach, at least 30 minutes before a meal.

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

5. What should I know while using Omeprazole ADVZ?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using Omeprazole ADVZ.
  • Tell your doctor if you become pregnant while you are taking Omeprazole ADVZ.
  • Tell your doctor if your reflux symptoms return after you stop taking Omeprazole ADVZ.
Looking after your medicine
  • Dry powder: Store below 25°C. Store in the original foil pouch to protect from light and moisture.
  • Reconstituted suspension: Store the reconstituted suspension in a refrigerator (2°C - 8°C). Store in the original container to protect from light. Keep the bottle tightly closed. It may be stored below 25°C for up to 2 days.

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

6. Are there any side effects?

There are a number of side effects associated with this medicine. It is important to be aware of them so that you can identif y any symptoms if they occur (see the full CMI for more details). The most common and serious side effects are headache, stomach and/or bowel complaints, nausea or vomiting, skin reactions, swelling of hands/feet or ankles, jaundice, ulcers/blisters/bleeding, blood in urine or faeces, or serious allergic reaction (swelling of the face, lips, mouth or throat which may cause difficulty in swallowing or breathing).

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 ADVZ Powder for oral suspension 2 mg/mL & 4 mg/mL

Active ingredient(s): omeprazole

Consumer Medicine Information (CMI)

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

Where to find information in this leaflet:

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

1. Why am I using Omeprazole ADVZ?

Omeprazole ADVZ contains the active ingredient omeprazole. Omeprazole ADVZ is 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.

Omeprazole ADVZ is used to treat the following conditions:

Reflux oesophagitis

Omeprazole ADVZ is used to treat the symptoms of reflux oesophagitis or reflux disease in adults and in children. This can be caused by "washing back" (reflux) of food and acid from the stomach into the gullet (oesophagus).

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

Omeprazole ADVZ is also used to help stop reflux oesophagitis coming back or relapsing.

Peptic ulcers

Omeprazole ADVZ 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.

Omeprazole ADVZ is also used to help stop gastric or duodenal ulcers coming back.

Omeprazole ADVZ also helps to relieve upper abdominal pain or discomfort that is often, but not always, related to eating.

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 Omeprazole ADVZ is taken with antibiotics, they will kill Helicobacter pylori and let your peptic ulcer heal. When Omeprazole ADVZ is taken together with two antibiotics, they are more effective than taken one or two at a time. It is possible that the antibiotics may not always kill Helicobacter pylori. You may need further treatment.

Peptic ulcers associated with Non-steroidal Anti-Inflammatory Drugs (NSAIDs)

Some peptic ulcers are caused by taking medicines called non-steroidal anti-inflammatory drugs. These medicines are commonly taken to treat joint disease or arthritis. Omeprazole ADVZ is also used to heal and prevent ulcers associated with NSAIDs.

Children over 1 month of age

Reflux oesophagitis and treatment of symptoms of gastro-oesophageal reflux disease (GORD). This is where acid from the stomach escapes into the gullet (the tube which connects your throat to your stomach) causing pain, inflammation and heartburn.

In children, the symptoms of the condition can include the return of stomach contents into the mouth (regurgitation), being sick (vomiting) and poor weight gain.

2. What should I know before I use Omeprazole ADVZ?

Warnings

Do not use Omeprazole ADVZ if:

  • you are allergic to omeprazole, or any of the ingredients listed at the end of this leaflet. Always check the ingredients to make sure you can use this medicine.
  • you are taking cilostazol, a medicine used to treat intermittent claudication (cramp-like pain in one or both legs).

Check with your doctor if you:

  • are allergic to proton-pump inhibitors
  • have been diagnosed with osteoporosis
  • have any problems with your liver
  • have ever had a skin reaction after treatment with a medicine similar to omeprazole that reduces stomach acid
  • take clopidogrel (medicine used to prevent blood clots), or medicines used to treat viral infections such as atazanavir and nelfinavir.

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 ADVZ 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.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

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.

Tell your doctor if you are taking any other medicines, including:

  • cilostazol - a medicine used to treat intermittent claudication (cramp-like pain in one or both legs)
  • warfarin and clopidogrel - medicines used to prevent blood clots
  • atazanavir and nelfinavir - medicines used to treat viral infections such as HIV
  • phenytoin – a medicine used to treat epilepsy or fits
  • digoxin - a medicine used to treat heart conditions
  • diazepam - a medicine used to treat anxiety and some other conditions
  • ketoconazole, itraconazole, voriconazole - medicines used to treat fungal infection
  • St John's Wort - a herbal remedy used to treat mood disorders
  • clarithromycin or rifampicin - medicines used to treat infections
  • 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
  • citalopram / escitalopram – medicines used to treat depression.

Some medicines may interfere with Omeprazole ADVZ and affect how it works.

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 ADVZ.

4. How do I use Omeprazole ADVZ?

How much to take

Your doctor will tell you how much medicine to take and how long to take it for. This will depend on your condition and how old you are.

For doses of ≤ 15 mg, the 2 mg/mL strength is recommended. For doses of 20 mg or 40 mg, the 4 mg/mL strength is suitable.

Adults

The dose of Omeprazole ADVZ is usually 20 mg a day, but 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

The recommended dose in children over 1 month of age to 1 year of age is 1 mg/kg once daily. Your doctor will calculate how much omeprazole your child should take. The recommended dose in children over one year of age is 10 mg once a day in children weighing 10 - 20 kg and 20 mg in children weighing more than 20 kg.

Follow the instructions provided and use Omeprazole ADVZ until your doctor tells you to stop.

When to take Omeprazole ADVZ

Omeprazole ADVZ should be taken at about the same time each day, preferably in the morning. Take on an empty stomach, at least 30 minutes before a meal. Keeping a regular time for taking Omeprazole ADVZ will help to remind you to take it.

How to prepare Omeprazole ADVZ and how to measure the dose

Please refer to section INSTRUCTIONS FOR USE at the end of this leaflet.

If you forget to take Omeprazole ADVZ

Omeprazole ADVZ should be taken 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 take too much Omeprazole ADVZ

If you think that you have taken too much Omeprazole ADVZ, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26 - Australia, or 0800 POISON or 0800 764 766 – New Zealand), 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 Omeprazole ADVZ?

Things you should do

You must use Omeprazole ADVZ exactly as your doctor has prescribed.

Remind any doctor, dentist or pharmacist you visit that you are using Omeprazole ADVZ.

Tell your doctor if you become pregnant while you are taking Omeprazole ADVZ.

Tell your doctor if your reflux symptoms return after you stop taking Omeprazole ADVZ.

Looking after your medicine

  • Dry powder: Store below 25°C. Store in the original foil pouch to protect from light and moisture.
  • Reconstituted suspension: Store the reconstituted suspension in a refrigerator (2°C - 8°C) for up to 28 days. Store in the original container to protect from light. Keep the bottle tightly closed. It may be stored below 25°C for up to 2 days.

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

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.

When to discard your medicine

Discard the medicine 28 days from date of preparation.

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 are all mild side effects:
  • constipation
  • nausea or vomiting
  • diarrhoea and wind (flatulence)
  • headache
  • stomach pain.
Some people may notice:
  • skin rash, itchy skin
  • muscle pain or weakness
  • dizziness
  • "pins and needles"
  • changes in sleep patterns
  • mood changes, confusion or depression
  • increase in breast size (males)
  • fever
  • increased bruising
  • dry or sore mouth
  • blurred vision
  • increased sweating
  • hair loss
  • tremor.
  • treatment > 3 month possibly decrease magnesium blood levels resulting in fatigue, involuntary muscle contractions, disorientation, convulsions, dizziness or increased heart rate
  • low magnesium blood levels may cause decrease of potassium or calcium levels in blood
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
  • 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.
The following side effects are more likely to arise from the ulcer itself rather than the treatment:
  • pain or indigestion during treatment with Omeprazole ADVZ
  • beginning to vomit blood or food
  • passing black (blood-stained) motions.
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.

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 (Australia). 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 ADVZ contains

Active ingredient
(main ingredient)		Omeprazole
Other ingredients
(inactive ingredients)
  • Sodium hydrogen carbonate
  • Potassium hydrogen carbonate
  • Sodium alginate
  • Maltitol
  • Mannitol
  • Sucralose
  • Xanthan gum
  • Vanilla flavour (for omeprazole 2 mg only)
  • Menthol flavour
  • Titanium dioxide
  • Sodium benzoate
  • Sodium methyl parahydroxybenzoate

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

What Omeprazole ADVZ looks like

Omeprazole ADVZ is packed in an amber plastic bottle with powder, fitted with a red closure cap also containing powder, all enclosed in an aluminium foil pouch. Each pack also contains a bottle adapter, an oral dosing syringe and a replacement cap.

Each bottle contains 47 g of powder for oral suspension. Once reconstituted, the bottle contains 90 mL of oral suspension, of which 75 mL is intended for dosing and administration.

Before reconstitution: White / off-white / slightly yellow powder in a cap attached to a bottle containing white / off-white / slightly yellow powder, which may contain dark specks due to sweetener.

After reconstitution: White / off-white / brownish oral suspension. May contain dark specks due to sweetener.

Omeprazole ADVZ - Powder for oral suspension 2 mg/mL: Aust R 391771

Omeprazole ADVZ - Powder for oral suspension 4 mg/mL: Aust R 391772

Who distributes Omeprazole ADVZ

Distributed in Australia by:

Boucher & Muir Pty Ltd t/a ADVANZ PHARMA (Australia)
Level 9, 76 Berry Street
North Sydney NSW 2060

Ph: 1800 627 680

Distributed in New Zealand by:

BNM Group
39 Anzac Road
Browns Bay
Auckland 0753

Ph: 0800 565 633

This leaflet was revised in April 2023.

INSTRUCTIONS FOR USE

It is recommended that a pharmacist reconstitutes Omeprazole ADVZ oral suspension prior to its dispensing to the patient.

Preparing and taking the suspension

The container is two compartment system containing powder both in the cap and in the bottle. The two powders first need to be combined and are then to be reconstituted in water. A red mixing disk will drop into the medicine to help mix the powders and also mix the reconstituted suspension after addition of the water. It should remain in the bottle. The red cap is replaced by a grey cap after reconstitution.

Instructions for initial reconstitution

Combination of powder in cap and bottle

  • Shake the bottle for 10 seconds to loosen the powder.
  • Twist the red cap anti-clockwise (see arrow on cap) until the seal is broken to release the powder in the red cap into the bottle.
  • Twist the red cap back to the original position, securely fastening the red cap onto the bottle.

Reconstitution of the powder

  • Shake the bottle vigorously for 10 seconds to mix the powders.
  • Tap the base of the bottle three times on a hard-horizontal surface to make sure all powder is in the bottle and not in the cap.
  • Remove the red cap from the bottle.
  • Add 64 mL of water by using a suitable measuring device.
  • Securely fasten the red cap onto the bottle and shake vigorously for 30 seconds.

Placement of syringe adaptor

  • Remove the red cap and red ring and throw away.
  • Insert the colourless, transparent bottle adaptor and replace the red cap with the grey plastic screw-cap.
  • Leave for 15 minutes for product to reach final consistency.

The reconstituted suspension will be a white / off-white / brownish suspension. It may contain dark specks due to the sweetener.

Measuring your dose

Instructions for use of the syringe

  1. Shake for 20 seconds immediately prior to each use.
  2. To open the bottle, press the grey cap down and turn it anti-clockwise (Figure 1). Do not remove the white cap portion.
  3. Take the syringe and put it into the adaptor opening (Figure 2).
  4. Turn the bottle upside down (Figure 3).
  5. Fill the syringe with a small amount of suspension by pulling the plunger down (Figure 4A).
Then push the plunger upward in order to remove any possible bubbles (Figure 4B).
Finally, pull the plunger down to the graduation mark corresponding to the quantity in millilitres (mL) prescribed by your doctor.
The top flat edge of the piston should be in line with the graduation mark you are measuring to (Figure 4C).
  1. Turn the bottle the right way up (Figure 5A).
  2. Remove the syringe from the adaptor (Figure 5B).
  3. Put the end of the syringe into the mouth of the patient and push the plunger slowly back in to take the medicine. The suspension will be released slowly while the last portion will be released faster due to reduced resistance in the tip of the syringe.
  4. Wash the syringe with water and let it dry before you use it again (Figure 6).
  5. Close the bottle with the grey plastic screw cap - leave the bottle adaptor in the bottle.

Note: It is normal to have the red plastic disc in the suspension during use; do not attempt to remove it.

Instruction for administration via nasogastric (NG) or percutaneous endoscopic gastrostomy (PEG) tubes

Ensure that the enteral feeding tube is free from obstruction before administration.

  1. Flush the enteral tube with 5 mL of water.
  2. Administer the required dose of omeprazole oral suspension with a suitable measuring device.
  3. Flush the enteral tube with 5 mL of water.

This product is compatible for use with polyurethane and PVC nasogastric (NG) and percutaneous endoscopic gastrostomy (PEG) tubes of size 6 Fr to 16 Fr. For the smallest diameter tubes (6 Fr) a smaller flush volume of 2 mL may be used to support the use in very young children where fluid intake restriction may be of relevance.

Published by MIMS December 2023

BRAND INFORMATION

Brand name

Omeprazole ADVZ

Active ingredient

Omeprazole

Schedule

S4

 

1 Name of Medicine

Omeprazole.

2 Qualitative and Quantitative Composition

Omeprazole ADVZ 2 mg/mL powder for oral suspension: After reconstitution, each 1 mL of suspension contains 2 mg of omeprazole. Each reconstituted bottle (90 mL) contains 180 mg of omeprazole.
Omeprazole ADVZ 4 mg/mL powder for oral suspension: After reconstitution, each 1 mL of suspension contains 4 mg of omeprazole. Each reconstituted bottle (90 mL) contains 360 mg of omeprazole.

Excipients with known effect.

Each 1 mL of suspension contains sodium methyl hydroxybenzoate 2.3 mg, maltitol 272 mg, sodium benzoate 5 mg, sodium 17.2 mg and potassium 54.3 mg.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder for oral suspension.

Powder in cap.

White/off-white/slightly yellow powder.

Powder in bottle.

White/off-white/slightly yellow powder. May contain dark specks due to sweetener.
When reconstituted, it will be a white/off-white/brownish suspension. It may contain dark specks due to the sweetener.

4 Clinical Particulars

4.1 Therapeutic Indications

Omeprazole ADVZ is indicated for:

Adults.

Treatment of duodenal ulcers.
Prevention of relapse of duodenal ulcers.
Treatment of gastric ulcers.
Prevention of relapse of gastric ulcers.
In combination with appropriate antibiotics, Helicobacter pylori (H. pylori) eradication in peptic ulcer disease.
Treatment of NSAID-associated gastric and duodenal ulcers.
Prevention of NSAID-associated gastric and duodenal ulcers in patients at risk.
Treatment of reflux oesophagitis.
Long-term management of patients with healed reflux oesophagitis.
Treatment of symptomatic gastro-oesophageal reflux disease (GORD).

Paediatric use.

Children over 1 month of age.

Treatment of reflux oesophagitis.
Symptomatic treatment of heartburn and acid regurgitation in GORD.

Children over 4 years of age and adolescents.

In combination with antibiotics in treatment of duodenal ulcer caused by H. pylori.

4.2 Dose and Method of Administration

Omeprazole ADVZ is recommended to be given in the morning.
Omeprazole ADVZ 2 mg/mL oral suspension is suitable for doses of ≤ 15 mg. For doses of 20 mg or greater, Omeprazole ADVZ 4 mg/mL oral suspension is suitable.

Symptomatic GORD.

Recommended dose for symptom relief.

Omeprazole 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 omeprazole 20 mg daily, further investigation is recommended.

Erosive oesophagitis.

Recommended healing dosage.

Omeprazole 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, omeprazole 40 mg once daily usually produces healing within 8 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 nonsteroidal 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.

Omeprazole 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, omeprazole 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 nonsteroidal anti-inflammatory drugs (NSAIDs), the recommended dose is omeprazole 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.

Omeprazole 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, omeprazole 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 nonsteroidal anti-inflammatory drugs (NSAIDs), the recommended dose is omeprazole 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 omeprazole 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 omeprazole 20 mg once daily.

Use in children.

Children over 1 month of age. Treatment of reflux oesophagitis.
Symptomatic treatment of heartburn and acid regurgitation in GORD.
See Table 1.
The 2 mg/mL and 4 mg/mL strengths are equivalent with respect to buffering capacity (same amount of buffer on a mL basis).
For doses of ≤ 15 mg, the 2 mg/mL strength is recommended. The 2 mg/mL strength is indicated for age 1 month to 1 year for administering up to 15 mg, and ≥ 1 year of age for administering 10 mg, to provide sufficient buffering capacity and absorption.
For doses of 20 mg or 40 mg, the 4 mg/mL strength is suitable.
The 4 mg/mL strength is suitable for the administration of higher doses such as 20 mg (5 mL) or 40 mg (10 mL).

Reflux oesophagitis.

The treatment time is 4-8 weeks.

Symptomatic treatment of heartburn and acid regurgitation in gastro-oesophageal reflux disease.

The treatment time is 2-4 weeks. If symptom control has not been achieved after 2-4 weeks the patient should be investigated further.
Children over 4 years of age and adolescents. Treatment of duodenal ulcer caused by H. pylori.
When selecting appropriate combination therapy, consideration should be given to official national, regional and local guidance regarding bacterial resistance, duration of treatment (most commonly 7 days but sometimes up to 14 days), and appropriate use of antibacterial agents. The treatment should be supervised by a specialist. See Table 2.

Elderly.

No dosage adjustment of omeprazole 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.

Method of administration.

Omeprazole oral suspension should be taken on an empty stomach, at least 30 minutes before a meal.

Precautions to be taken before handling or administering the medicinal product.

Omeprazole powder for oral suspension requires reconstitution prior to oral administration. For instructions on reconstitution of the medicinal product before administration, see Section 6.6 Special Precautions for Disposal.
For instructions for administration via nasogastric (NG) or percutaneous endoscopic gastrostomy (PEG) tubes (see Section 6.6 Special Precautions for Disposal).

Preparing and taking the suspension.

It is recommended that a pharmacist reconstitutes Omeprazole ADVZ oral suspension prior to dispensing to the patient.
The container is a two compartment system containing powder both in the cap and in the bottle. The two powders first need to be combined and are then to be reconstituted in water. A red mixing disk will drop into the medicine to help mix the powders and also mix the reconstituted suspension after addition of the water. It should remain in the bottle. The red cap is replaced by a grey cap after reconstitution.
Instructions for initial reconstitution.

Combination of powder in cap and bottle.

Shake the bottle for 10 seconds to loosen the powder.
Twist the red cap anti-clockwise (see arrow on cap) until the seal is broken to release the powder in the red cap into the bottle.
Twist the red cap back to the original position, securely fastening the red cap onto the bottle.

Reconstitution of the powder.

Shake the bottle vigorously for 10 seconds to mix the powders.
Tap the base of the bottle three times on a hard-horizontal surface to make sure all powder is in the bottle and not in the cap.
Remove the red cap from the bottle.
Add 64 mL of water by using a suitable measuring device.
Securely fasten the red cap onto the bottle and shake vigorously for 30 seconds.

Placement of syringe adaptor.

Remove the red cap and red ring and throw away.
Insert the colourless, transparent bottle adaptor and replace the red cap with the grey plastic screw-cap.
Leave for 15 minutes for product to reach final consistency.
The reconstituted suspension will be a white/off-white/brownish suspension. It may contain dark specks due to the sweetener.
Measuring the dose.

Instructions for use of the syringe.

1. Shake for 20 seconds immediately prior to each use.
2. To open the bottle, press the grey cap down and turn it anti-clockwise. Do not remove the white cap portion.
3. Take the syringe and put it into the adaptor opening.
4. Turn the bottle upside down.
5. Fill the syringe with a small amount of suspension by pulling the plunger down.
Then push the plunger upward in order to remove any possible bubbles. Finally, pull the plunger down to the graduation mark corresponding to the quantity in millilitres (mL) prescribed.
The top flat edge of the piston should be in line with the graduation mark you are measuring to.
6. Turn the bottle the right way up.
7. Remove the syringe from the adaptor.
8. Put the end of the syringe into the mouth of the patient and push the plunger slowly back in to take the medicine. The suspension will be released slowly while the last portion will be released faster due to reduced resistance in the tip of the syringe.
9. Wash the syringe with water and let it dry before you use it again.
10. Close the bottle with the grey plastic screw cap - leave the bottle adaptor in the bottle.

Note.

It is normal to have the red plastic disc in the suspension during use; do not attempt to remove it.
Instructions for administration via nasogastric (NG) or percutaneous endoscopic gastrostomy (PEG) tubes. Ensure that the enteral feeding tube is free from obstruction before administration.
1. Flush the enteral tube with 5 mL of water.
2. Administer the required dose of omeprazole oral suspension with a suitable measuring device.
3. Flush the enteral tube with 5 mL of water.
This product is compatible for use with polyurethane and PVC nasogastric (NG) and percutaneous endoscopic gastrostomy (PEG) tubes of size 6 Fr to 16 Fr. For the smallest diameter tubes (6 Fr) a smaller flush volume of 2 mL may be used to support the use in very young children where fluid intake restriction may be of relevance.

4.3 Contraindications

Hypersensitivity to omeprazole, 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 effect 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 omeprazole. The occurrence of SCLE with previous PPI treatment may increase the risk of SCLE with other PPIs.

Hypomagnesaemia.

Hypomagnesaemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs. Severe hypomagnesaemia may result in serious adverse events such as tetany, seizures and potentially also arrhythmias. In some patients, treatment of hypomagnesaemia with magnesium replacement was not sufficient to correct the magnesium imbalance and discontinuation of the PPI was required. In patients later retreated with the same or different PPI, hypomagnesaemia returned within a shorter time period. For patients expected to be on prolonged treatment or who take PPIs with other medicines such as digoxin or medicines that may cause hypomagnesaemia (e.g. diuretics), consideration should be given to monitoring magnesium levels prior to initiation and periodically thereafter.
Hypomagnesaemia may lead to hypocalcaemia and/or hypokalaemia (see Section 4.8 Adverse Effects (Undesirable Effects)).

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 omeprazole 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.

Citalopram/escitalopram.

Co-administration of omeprazole (20 mg) with citalopram (20 mg single dose) doubles the AUC of the S-isomer of citalopram, but the R-isomer of citalopram is not affected. A reduction in the dose of citalopram may be necessary based on clinical judgement. For patients taking omeprazole, the citalopram dose should not exceed the maximum dose of 20 mg/day.
Co-administration of omeprazole (30 mg) with escitalopram (20 mg single dose) increased the plasma levels (approximately 50%) and terminal half-life (31%) of escitalopram. A reduction in the dose of escitalopram may be necessary based on clinical judgement.

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, oestradiol, erythromycin and budesonide).

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)

Omeprazole suspension is 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). Hypomagnesaemia may result in hypokalaemia and/or hypocalcaemia.

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.

Paediatric population.

The safety of omeprazole has been assessed in a total of 310 children aged 0 to 16 years with acid-related disease. There are limited long term safety data from 46 children who received maintenance therapy of omeprazole during a clinical study for severe erosive oesophagitis for up to 749 days. The adverse event profile was generally the same as for adults in short- as well as in long-term treatment. There are no long-term data regarding the effects of omeprazole treatment on puberty and growth.

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 http://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.

Omeprazole 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% in 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 3.

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.
In a non-controlled study in children (1 to 16 years of age) with severe reflux oesophagitis, omeprazole at doses of 0.7 to 1.4 mg/kg improved oesophagitis level in 90% of the cases and significantly reduced reflux symptoms. In a single-blind study, children aged 0-24 months with clinically diagnosed gastro-oesophageal reflux disease were treated with 0.5, 1.0 or 1.5 mg omeprazole/kg. The frequency of vomiting/regurgitation episodes decreased by 50% after 8 weeks of treatment irrespective of the dose.
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 therefore administered in omeprazole oral suspension as a buffered suspension. The buffer protects omeprazole from acid degradation, facilitating absorption.
Absorption of omeprazole is rapid, with peak plasma levels occurring approximately 30 minutes after dose. Absorption of omeprazole takes place in the small intestine and is usually completed within 3-6 hours. In a bioavailability study, the administration with food (milk) reduced the extent of absorption by approximately 20%. The systemic availability (bioavailability) from a single oral dose of omeprazole is approximately 40%. After repeated once-daily administration, the bioavailability increases to about 60%.

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 hydroxy-omeprazole, 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 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 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.
In children younger than 6 months, clearance of omeprazole is low due to low capacity to metabolise omeprazole.

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

Omeprazole ADVZ contains sodium bicarbonate, potassium bicarbonate, sodium alginate, maltitol, mannitol, sucralose, xanthan gum, vanilla flavour, mint flavour, titanium dioxide, sodium benzoate and sodium methyl hydroxybenzoate.

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

Dry powder.

Store below 25°C. Store in the original foil pouch to protect from light and moisture.

Reconstituted suspension.

Store the reconstituted suspension in a refrigerator (2°C-8°C) for up to 28 days.
Store in the original container to protect from light. Keep the bottle tightly closed. It may be stored below 25°C for up to 2 days.

6.5 Nature and Contents of Container

Amber plastic (PET) bottle with powder, fitted with a red polypropylene (PP) closure cap containing powder, all enclosed in an aluminium foil pouch.
Each bottle contains 47 g of powder for oral suspension. Once reconstituted, the bottle contains 90 mL of oral suspension, of which 75 mL is intended for dosing and administration.
Each pack also contains an opaque PP oral dosing syringe (5 mL, graduated at each 1 mL and intermediate marks every 0.1 mL) with white HDPE plunger, colourless, transparent LDPE bottle adaptor and grey PP replacement cap.

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

The chemical name is 5-methoxy-2-[(RS)-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl]-1H-benzimidazole. Omeprazole is a white or almost white powder which is very slightly soluble in water, soluble in methylene chloride, sparingly soluble in ethanol (96%) and in methanol. It dissolves in dilute solutions of alkali hydroxides.

Chemical structure.


Molecular formula: C17H19N3O3S.
Molecular weight: 345.4.

CAS number.

73590-58-6.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.