Consumer medicine information

Esomeprazole GH

Esomeprazole

BRAND INFORMATION

Brand name

Esomeprazole GH

Active ingredient

Esomeprazole

Schedule

SUMMARY CMI

Esomeprazole GH

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 Esomeprazole GH?

Esomeprazole GH contains the active ingredient esomeprazole magnesium trihydrate. Esomeprazole GH is used to treat Reflux Oesophagitis, Upper gastrointestinal symptoms associated with non-steroidal anti-inflammatory drugs (NSAIDs) therapy, Peptic Ulcers Associated with Helicobacter pylori Infection, Zollinger-Ellison Syndrome and Bleeding Peptic Ulcers.

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

2. What should I know before I use Esomeprazole GH?

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

Talk to your doctor or pharmacist 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 Esomeprazole GH? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Esomeprazole GH 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 Esomeprazole GH?

Esomeprazole GH is available as either tablets or as granules for suspension in sachets. The dose of Esomeprazole GH tablets is usually 20 mg or 40 mg a day. The dose of Esomeprazole GH sachets is 10 mg to 20 mg a day. The dose for tablets or sachets depends on what condition you are being treated for and how severe it is.
Follow all directions given to you by your doctor and pharmacist carefully.

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

5. What should I know while using Esomeprazole GH?

Things you should do	Remind any doctor, dentist or pharmacist you visit that you are using Esomeprazole GH. Tell your doctor if you become pregnant while you are taking Esomeprazole GH. Tell your doctor if your symptoms return.
Things you should not do	Do not take Esomeprazole GH to treat any other complaints unless your doctor tells you to. Do not give this medicine to anyone else, even if their symptoms seem similar to yours.
Driving or using machines	Be careful before you drive or use any machines or tools until you know how Esomeprazole GH affects you.
Looking after your medicine	Keep your Esomeprazole GH in the blister pack or sachet until it is time to take it. Keep it in a cool, dry place where the temperature stays below 25°C.

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

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. These include nausea or vomiting, constipation, diarrhoea, headache, wind, stomach pain, skin rash, itchy skin, dizziness or dry mouth. However, some serious side effects may need urgent medical attention. These include shortness of breath, wheezing or difficulty breathing, swelling of the face, lips, tongue or other parts of the body, severe skin reaction which may include rash, itching, redness, blistering or peeling of the skin, signs of liver inflammation including yellowing of the skin or eyes, feeling generally unwell, nausea, vomiting, loss of appetite, blood in the urine and increased or decreased urine output.

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

Esomeprazole GH

Active ingredient(s): esomeprazole magnesium trihydrate

Consumer Medicine Information (CMI)

This leaflet provides important information about using Esomeprazole GH. 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 Esomeprazole GH.

Where to find information in this leaflet:

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

1. Why am I using Esomeprazole GH?

Esomeprazole GH contains the active ingredient esomeprazole magnesium trihydrate. Esomeprazole GH 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

Esomeprazole GH is used to treat reflux oesophagitis. 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. Esomeprazole GH is also taken to help stop reflux oesophagitis coming back or relapsing.

Upper gastrointestinal symptoms associated with non steroidal anti-inflammatory drugs (NSAIDs) therapy

Esomeprazole GH is taken to treat the symptoms of pain or discomfort, in the stomach caused by NSAIDs, a type of medicine for pain or inflammation.

Esomeprazole GH is also taken to help heal and prevent ulcers caused by NSAIDs.

Peptic Ulcers Associated with Helicobacter pylori Infection

Most people who have a peptic (gastric and duodenal) ulcer also have a bacterium called Helicobacter pylori in their stomach.

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. If you have a peptic ulcer, your doctor will prescribe Esomeprazole GH with antibiotics. When Esomeprazole GH and antibiotics are taken together, they work to kill the bacterium and let your ulcer heal. You may need further treatment with antibiotics.

Zollinger-Ellison Syndrome

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

Bleeding Peptic Ulcers

When peptic ulcers become severe enough, they start to bleed. You may receive treatment injected into your veins initially. This treatment may be followed with Esomeprazole GH tablets or granules prescribed by your doctor for a longer period of time. This is to help your ulcer/s to heal.

2. What should I know before I use Esomeprazole GH?

Warnings

Do not use Esomeprazole GH if:

you are allergic to esomeprazole magnesium trihydrate, 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 allergic to any medicines containing proton pump inhibitors.

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.

Do not take Esomeprazole GH if you are also taking atazanavir or cilostazol. Please check with your doctor or pharmacist if you are taking these medicines. These medicines will be affected by Esomeprazole GH.

Check with your doctor or pharmacist if you have:

allergies to any other medicines, foods, dyes or preservatives;
any problems with your liver;
severe kidney problems;
any other medical conditions;
been diagnosed with osteoporosis;
ever had a skin reaction after treatment with a medicine similar to Esomeprazole GH that reduces stomach acid.

There is no evidence that Esomeprazole GH is addictive.

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

Check with your doctor or pharmacist if you are pregnant or intend to become pregnant.

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

It is not known if it is safe for you to take Esomeprazole GH while you are pregnant. It may affect your baby.

It is not known if your baby can take in Esomeprazole GH from breast milk if you are breastfeeding.

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

Children younger than 1 year:

Esomeprazole GH is not approved for use in children younger than 1 year of age. There is no specific information about use in children younger than 1 year of age, so Esomeprazole GH is not recommended in these patients..

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 Esomeprazole GH if you are taking the following medicines:

atazanavir and nelfinavir - medicines used to treat viral infections such as HIV;
cilostazol - a medicine used to treat intermittent claudication.

Some medicines may interfere with Esomeprazole GH and affect how it works. These include:

ketoconazole, itraconazole and voriconazole - medicines used to treat fungal infections
diazepam - a medicine used to treat anxiety and some other conditions;
phenytoin - a medicine used to treat epilepsy or fits;
citalopram, clomipramine and imipramine - medicines used to treat depression;
St John's wort - a herbal remedy used to treat mood disorders;
clarithromycin and rifampicin - medicines used to treat bacterial infections;
warfarin and clopidogrel - medicines used to prevent blood clots;
digoxin - a medicine used to treat heart conditions;
methotrexate - a medicine used to treat arthritis and some types of cancer;
tacrolimus and mycophenolate mofetil - medicines used to assist in organ transplants;
erlotinib or related medicines used to treat cancer.

These medicines may be affected by Esomeprazole GH 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.

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

4. How do I use Esomeprazole GH?

How much to take

Take one Esomeprazole GH tablet each day, unless your doctor has told you otherwise.
The dose of Esomeprazole GH tablets is usually 20 mg or 40 mg a day depending on what condition you are being treated for and how severe it is.

When to take / use Esomeprazole GH

Esomeprazole GH should be used at about the same time each day.
Keeping a regular time for taking Esomeprazole GH will help to remind you to take it.
Esomeprazole GH can be taken with food or on an empty stomach.
Keep taking Esomeprazole GH for as long as your doctor recommends.
In most patients, Esomeprazole GH relieves symptoms rapidly and healing is usually complete within 4 weeks.

How to take Esomeprazole GH

Swallow Esomeprazole GH tablets 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. If you have difficulty swallowing the tablets:

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

If you cannot swallow at all, follow steps 1-3 above to disperse the tablets and administer the liquid and pellets through a gastric tube.

If you forget to use Esomeprazole GH

Esomeprazole GH 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 Esomeprazole GH

If you think that you have used too much Esomeprazole GH, 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 Esomeprazole GH?

Things you should do

Take Esomeprazole GH exactly as your doctor has prescribed.

If you are about to start on any new medicine, tell your doctor, dentist or pharmacist that you are taking Esomeprazole GH.

Tell all doctors, dentists and pharmacists who are treating you that you are taking Esomeprazole GH.

Tell your doctor if you become pregnant while you are taking Esomeprazole GH.

Tell your doctor if your symptoms return.

Although Esomeprazole GH 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 Esomeprazole GH, tell your doctor.

It may affect the results of some tests.

Things you should not do

Do not take it to treat any other complaints unless your doctor tells you to.
Do not give this medicine to anyone else, even if their symptoms seem similar to yours.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Esomeprazole GH affects you.

Looking after your medicine

Keep your Esomeprazole GH in the blister pack or sachet until it is time to take it. If you take Esomeprazole GH out of the blister pack or sachet it will not keep well.
Keep it in a cool, dry place where the temperature stays below 25°C.

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

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

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

Keep it where young children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

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.

Less serious side effects

Less serious side effects	What to do
nausea or vomiting constipation diarrhoea headache wind stomach pain skin rash, itchy skin dizziness dry mouth	Speak to your doctor if you have any of these less serious side effects and they worry you.
blurred vision mood changes, confusion or depression muscle pain or weakness joint pain increase in breast size (males) increased sweating changes in sleep patterns fever increased bruising "pins and needles" hair loss tremor skin reaction, especially in sun-exposed areas, with joint pain muscle twitching or jerking movements irregular (fast or slow) heartbeat loss of consciousness or awareness	Speak to your doctor immediately if you have any of these side effects. These side effects may require medical attention.

Serious side effects

Serious side effects	What to do
shortness of breath, wheezing or difficulty breathing swelling of the face, lips, tongue or other parts of the body severe skin reaction which may include rash, itching, redness, blistering or peeling of the skin signs of liver inflammation including yellowing of the skin or eyes, feeling generally unwell, nausea, vomiting, loss of appetite blood in the urine increased or decreased urine output	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.
pain or indigestion during treatment with Esomeprazole GH you begin to vomit blood or food you pass black (blood-stained) motions	Contact your doctor immediately if you notice any of these side effects.

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

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. 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 Esomeprazole GH contains

Active ingredient (main ingredient)	Esomeprazole magnesium trihydrate
Other ingredients (inactive ingredients)	Non Pareil Seeds 40-50 (PI 108808) Hyprolose Crospovidone Icing sugar with maize starch (PI 109216) Magnesium oxide - light Purified talc Macrogol 6000 Methacrylic acid - ethyl acrylate copolymer (1:1) Glycerol Macrogol 400 Polysorbate 80 Hypromellose phthalate Microcrystalline cellulose Povidone Pregelatinised maize starch Silicon dioxide OPADRY complete film coating system 03B54193 PINK (PI 108604) OPADRY complete film coating system 03B84893 PINK (PI 108603) Iron oxide red Iron oxide yellow
Potential allergens	Sugars

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

What Esomeprazole GH looks like

Esomeprazole GH enteric-coated tablet 20 mg are light pink coloured, oblong, biconvex, coated tablets debossed with '20' on one side and ‘CE’ on the other. [AUST R 307865 (blister pack) and AUST R 307868 (HDPE pack)].

Esomeprazole GH enteric-coated tablet 40 mg are pink coloured, oblong, biconvex, coated tablets debossed with '40' on one side and ‘CE’ on the other side. [AUST R 307866 (blister pack) and AUST R 307867 (HDPE pack)].

Who distributes Esomeprazole GH

Generic Health Pty Ltd
Suite 2, Level 2
19-23 Prospect Street
Box Hill, VIC, 3128
Australia

ii1256301 [email protected]

ii1256302 +61 3 9809 7900

ii1256303 www.generichealth.com.au

This leaflet was prepared in February 2025.

Published by MIMS May 2025

BRAND INFORMATION

Brand name

Esomeprazole GH

Active ingredient

Esomeprazole

Schedule

Notes

Distributed by Generic Health Pty Ltd

1 Name of Medicine

Esomeprazole magnesium trihydrate.

2 Qualitative and Quantitative Composition

Esomeprazole GH (esomeprazole enteric-coated 20 mg and 40 mg tablets) is comprised of enteric-coated pellets containing esomeprazole (as magnesium trihydrate).
List of excipients with known effect: sugars.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Esomeprazole GH 20 mg enteric-coated tablets.

Light pink coloured, oblong, biconvex, coated tablets debossed with '20' on one side and 'CE' on the other.

Esomeprazole GH 40 mg enteric-coated tablets.

Pink coloured, oblong, biconvex, coated tablets debossed with '40' on one side and 'CE' on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

Esomeprazole GH (esomeprazole enteric-coated 20 mg and 40 mg tablet) is indicated for:

Gastro-oesophageal reflux disease (GORD).

Treatment of erosive reflux oesophagitis; long-term management of patients with healed oesophagitis to prevent relapse; symptomatic treatment of gastro-oesophageal reflux disease (GORD).

Patients requiring NSAID therapy.

Short-term treatment of upper gastrointestinal symptoms associated with non-steroidal anti-inflammatory drug NSAID (nonselective and COX-2 selective) therapy; healing of gastric ulcers associated with non-steroidal anti-inflammatory drug NSAID (non-selective and COX-2 selective) therapy; prevention of gastric and duodenal ulcers associated with non-steroidal anti-inflammatory drug NSAID (non-selective and COX-2 selective) therapy in patients at risk.

Prevention of rebleeding of gastric or duodenal ulcers following treatment with esomeprazole solution administered by intravenous infusion.

Pathological hypersecretory conditions including Zollinger-Ellison syndrome and idiopathic hypersecretion.

In combination with appropriate antibiotics for.

Healing of duodenal ulcer associated with Helicobacter pylori; eradication of Helicobacter pylori in patients with active or healed peptic ulcer.

4.2 Dose and Method of Administration

Esomeprazole GH enteric-coated tablets should be swallowed whole with liquid. The tablets should not be chewed or crushed.
If required, the tablets can also be dispersed in half a glass of non-carbonated water (mineral water is not suitable). No other liquids should be used. 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.
For patients who cannot swallow, the tablets can be dispersed in non-carbonated water and administered via a large syringe through a gastric tube. To ensure appropriate dosing and to avoid clogging, the gastric tube should be flushed with non-carbonated water following administration.

Adults.

Gastro-oesophageal reflux disease (GORD).

Treatment of erosive reflux oesophagitis.

40 mg once daily for 4 weeks. An additional 4 weeks treatment is recommended for patients in whom oesophagitis has not healed or who have persistent symptoms.

Long-term management (maintenance) of patients with healed oesophagitis to prevent relapse.

20 mg once daily.

Symptomatic treatment of gastro-oesophageal reflux disease (GORD).

In patients with normal endoscopy 20 mg once daily for 4 weeks. If symptom control has not been achieved after 4 weeks, the patient should be further investigated. For patients with symptom resolution after 4 weeks initial therapy, subsequent symptom control can be achieved using an on-demand regimen taking 20 mg once daily, when needed.
Patients requiring NSAID (non-selective and COX-2 selective) therapy.

Short-term treatment of upper gastrointestinal symptoms associated with NSAID therapy.

20 mg once daily in patients requiring NSAID therapy. If symptom control has not been achieved after 4 weeks, the patient should be further investigated. Controlled studies did not extend beyond 4 weeks.

Healing of gastric ulcers associated with NSAID (non-selective and COX-2 selective) therapy.

The usual dose is 20 mg once daily for 4 to 8 weeks.

Prevention of gastric and duodenal ulcers associated with NSAID (non-selective and COX-2 selective) therapy in patients at risk.

20 mg once daily. Controlled studies did not extend beyond 6 months.
Prevention of rebleeding of gastric or duodenal ulcers. 40 mg once daily for a duration determined by the treating physician. Oral esomeprazole should be preceded by esomeprazole administered intravenously.
Pathological hypersecretory conditions including Zollinger-Ellison syndrome and idiopathic hypersecretion. The recommended initial dosage is esomeprazole 40 mg twice daily. The dosage should then be individually adjusted and treatment continued as long as clinically indicated. Doses up to 120 mg twice daily have been administered.
In combination with appropriate antibiotics for. Healing of duodenal ulcer associated with Helicobacter pylori; and
Eradication of Helicobacter pylori with active or healed peptic ulceration.
20 mg esomeprazole twice daily for 7 days. In Section 5.1 (see Section 5.1 Pharmacodynamic Properties, Clinical trials), esomeprazole was used in combination with 1000 mg amoxycillin and 500 mg clarithromycin, both twice daily for 7 days.

Children and adolescents 12-18 years.

Treatment of erosive reflux oesophagitis.

40 mg once daily for 4 weeks. An additional 4 weeks treatment is recommended for patients in whom oesophagitis has not healed or who have persistent symptoms.

Long-term management (maintenance) of patients with healed oesophagitis to prevent relapse.

20 mg once daily.

Symptomatic treatment of gastro-oesophageal reflux disease (GORD).

In patients with normal endoscopy 20 mg once daily for 4 weeks. If symptom control has not been achieved after 4 weeks, the patient should be further investigated. Once symptoms have resolved, subsequent symptom control can be achieved using 20 mg once daily under medical supervision.

Children 1-11 years.

(Esomeprazole GH enteric-coated tablets are not available in 10 mg strength).
Gastro-oesophageal reflux disease (GORD).

Treatment of erosive reflux oesophagitis.

Weight < 20 kg: 10 mg once daily for 8 weeks.
Weight ≥ 20 kg: 10 mg or 20 mg once daily for 8 weeks.

Long-term management (maintenance) of patients with healed oesophagitis to prevent relapse.

10 mg once daily.

Symptomatic treatment of gastro-oesophageal reflux disease (GORD).

10 mg once daily for up to 8 weeks.
Doses over 1 mg/kg have not been studied.

Children below the age of 1 year.

Esomeprazole is not approved for use in children younger than 1 year.

Elderly.

Dose adjustment is not required in the elderly.

Hepatic impairment.

Dose adjustment is not required in patients with mild to moderate liver impairment (Child Pugh A and B). For patients with severe liver impairment (Child Pugh C), a maximum dose of 20 mg esomeprazole should not be exceeded (see Section 4.4 Special Warnings and Precautions for Use).

Renal impairment.

Dosage adjustment is not required in patients with impaired renal function. Due to limited experience in patients with severe renal insufficiency such patients should be treated with caution.

4.3 Contraindications

Known hypersensitivity to esomeprazole, substituted benzimidazoles or any other constituents of the formulation.
Esomeprazole like other proton pump inhibitors should not be administered with atazanavir (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Effects of esomeprazole on other drugs).
Esomeprazole, an inhibitor of CYP2C19, is contraindicated in patients taking cilostazol.

4.4 Special Warnings and Precautions for Use

As with all antisecretory agents, the presence of any alarm symptom (e.g. significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis or melaena) and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment with esomeprazole may alleviate symptoms and delay diagnosis.
Patients on long-term treatment (particularly those treated for more than a year) should be kept under regular surveillance.
Patients on on-demand treatment should be instructed to contact their physician if their symptoms change in character. When prescribing esomeprazole for on demand therapy, the implications for interactions with other pharmaceuticals, due to fluctuating plasma concentrations of esomeprazole should be considered (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
When prescribing esomeprazole for eradication of Helicobacter pylori possible drug interactions for all components in the triple therapy should be considered. Clarithromycin is a potent inhibitor of CYP3A4 and hence contraindications and interactions for clarithromycin should be considered when the triple therapy is used in patients concurrently taking other drugs metabolised via CYP3A4 such as cisapride.

Effects of acid inhibitions.

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

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 esomeprazole (40 mg p.o. daily) resulting in decreased exposure to the active metabolite of clopidogrel by an average of 40% and resulting in decreased maximum inhibition of (ADP induced) platelet aggregation by an average of 14%. Based on these data, concomitant use of esomeprazole and clopidogrel should be avoided (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Acute tubulointerstitial nephritis.

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

Cyanocobalamin (vitamin B-12) deficiency.

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

Osteoporotic fractures.

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

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 esomeprazole. 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. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesaemia required magnesium replacement and discontinuation of the PPI.
For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesaemia (e.g. diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically during PPI treatment.
Hypomagnesaemia may lead to hypocalcaemia and/or hypokalaemia (see Section 4.8 Adverse Effects (Undesirable Effects)).

Special patient populations.

Use in hepatic impairment. The metabolism of esomeprazole in patients with mild to moderate liver dysfunction (Child-Pugh A or B) may be impaired, however no dose adjustment is required. The metabolic rate is decreased in patients with severe liver dysfunction (Child-Pugh C) resulting in a doubling of the area under the plasma concentration-time curve for esomeprazole. Therefore, a maximum of 20 mg should not be exceeded in patients with severe dysfunction. Esomeprazole or its major metabolites do not show any tendency to accumulate with once daily dosing (see Section 4.2 Dose and Method of Administration).
Use in renal impairment. No studies have been performed in patients with decreased renal function. Since the kidney is responsible for the excretion of the metabolites of esomeprazole but not for the elimination of the parent compound, the metabolism of esomeprazole is not expected to be changed in patients with impaired renal function.
Use in the elderly. The metabolism of esomeprazole is not significantly changed in elderly subjects (71-80 years).
Paediatric use.

Children 12-18 years.

The pharmacokinetics of esomeprazole were studied in 28 adolescent patients with GORD aged 12 to 18 years, in a single centre study. Patients were randomised to receive esomeprazole 20 mg or 40 mg once daily for 8 days. Mean C_max and AUC values of esomeprazole were not affected by body weight or age; and more than dose proportional increases in mean C_max and AUC values were observed between the two dose groups in the study. Overall, esomeprazole pharmacokinetics in adolescent patients aged 12 to 18 years were similar to those observed in adult patients with symptomatic GORD (Table 1).

Children 1-11 years.

Following repeated dose administration of 10 mg and 20 mg esomeprazole, the total exposure (AUC) and the time to reach maximum plasma drug concentration (t_max) for the 10 mg dose was similar across the 1 to 11 year-olds and similar to the total exposure seen with the 20 mg dose in 12 to 18 year-olds and adults. The 20 mg dose resulted in higher exposure in 6 to 11 year-olds compared to 12 to 18 year-olds and adults (see Table 2).

Repeated dose administration of 5 mg esomeprazole resulted in insufficient exposure in 1 to 5 year-olds.
A single-centre, randomised, single-blind, two-arm parallel, repeated dose study examined the pharmacokinetics of esomeprazole and its efficacy in controlling intragastric pH in infants aged 1-24 months. Patients were randomised to either esomeprazole 0.25 mg/kg or 1.0 mg/kg orally once daily for 7 or 8 days. Fifty patients were randomised of which 43 were ≤ 12 months of age and 7 were > 12 months of age. Forty-five patients completed the study of whom 39 were ≤ 12 months of age and 6 were > 12 months of age. The median time to reach maximum plasma concentration (t_max) of esomeprazole was approximately 2 hours for the 0.25 mg/kg dose and 3 hours for the 1.0 mg/kg dose group. Mean AUC_T was 3.51 micromol.h/L for the 1.0 mg/kg dose and 0.65 micromol.h/L for the 0.25 mg/kg dose. Mean C_max values of 0.85 micromol/L and 0.17 micromol/L were obtained for the 1.0 mg/kg and 0.25 mg/kg doses respectively. Large inter-individual variability in AUC_t, AUC_T, and C_SSmax of esomeprazole was observed for both 0.25 mg/kg and 1.0 mg/kg doses and the variability seemed larger in the younger children. No conclusions regarding dose proportionality could be drawn. The mean percentage of time with intragastric pH > 4 increased from 30.5% at baseline to 47.9% in the 0.25 mg/kg dose group and from 28.6% to 69.3% in the 1.0 mg/kg dose group. Statistically, the increase was significantly higher with esomeprazole 1.0 mg/kg dose compared with the 0.25 mg/kg dose. Both doses of esomeprazole were well tolerated. Esomeprazole is not approved for use in children < 1 year of age.

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 population lack a functional CYP2C19 enzyme and are called poor metabolisers. In these individuals the metabolism of esomeprazole is most likely catalysed by CYP3A4. After repeated once-daily administration of 40 mg esomeprazole, the mean area under the plasma concentration-time curve was approximately 100% higher in poor metabolisers than in subjects having a functional CYP2C19 enzyme (extensive metabolisers). Mean plasma concentrations were increased by about 60%. These findings have no implications for the dosage of esomeprazole.

Gender.

Following a single dose of 40 mg esomeprazole the mean area under the plasma-concentration-time curve is approximately 30% higher in females than in males. No gender difference is seen after repeated once-daily administration. These findings have no implications for the dosage of esomeprazole.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Esomeprazole is metabolised via the CYP2C19 and CYP3A4 isoforms of the hepatic cytochrome P-450 system and may be expected to interact with the pharmacokinetics of other drugs metabolised by this system.
Esomeprazole inhibits CYP2C19, the major esomeprazole metabolising enzyme. Thus, when esomeprazole is combined with drugs metabolised by CYP2C19 (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Effects of esomeprazole on other drugs), the plasma concentrations of these drugs may be increased and a dose reduction could be needed. This should be considered especially when prescribing esomeprazole for on demand therapy.
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 esomeprazole (40 mg p.o. daily) resulting in decreased exposure to the active metabolite of clopidogrel by an average of 40%, and resulting in decreased maximum inhibition of (ADP induced) platelet aggregation by an average of 14%. Based on these data, concomitant use of esomeprazole 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.

Other drugs that affect esomeprazole.

Clarithromycin.

Concomitant administration of esomeprazole and a CYP3A4 inhibitor, clarithromycin (500 mg bid), resulted in a doubling of the exposure (AUC) to esomeprazole. Dose adjustment of esomeprazole is not required.
Concomitant administration of esomeprazole and a combined inhibitor of CYP2C19 and CYP3A4, such as voriconazole, may result in more than doubling of the esomeprazole exposure. However, dose adjustment of esomeprazole, with normal dosage, is not required.
CYP3A4 is a less important pathway than CYP2C19. However, inhibitors of CYP3A4 other than clarithromycin (e.g. ketoconazole, itraconazole, erythromycin etc) may also reduce esomeprazole clearance, although this is unlikely to be of any clinical significance.
Drugs known to induce CYP2C19 or CYP3A4 or both (such as rifampicin and St John's wort) may lead to decreased esomeprazole serum levels by increasing the esomeprazole metabolism.

Effects of esomeprazole on other drugs.

Cisapride.

In healthy volunteers, concomitant administration of esomeprazole 40 mg resulted in a 32% increase in area under the plasma concentration-time curve (AUC) and a 31% prolongation of elimination half-life (t_1/2) but no significant increase in peak plasma levels of cisapride. The slightly prolonged QTc interval observed after administration of cisapride alone, was not further prolonged when cisapride was given in combination with esomeprazole (see Section 4.4 Special Warnings and Precautions for Use).

Cilostazol.

Omeprazole as well as esomeprazole act as inhibitors of CYP2C19. Omeprazole, given in doses of 40 mg to healthy subjects in a cross-over study, increased C_max 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).

Citalopram, clomipramine and imipramine.

Because the plasma concentrations of these drugs may be increased by the concomitant administration of esomeprazole a dose reduction could be needed.

Diazepam.

Concomitant administration of 30 mg esomeprazole to healthy volunteers resulted in 45% decrease in clearance of the CYP2C19 substrate diazepam. This interaction is unlikely to be of clinical relevance.

NSAID drugs.

Studies evaluating concomitant administration of esomeprazole and either naproxen (non-selective NSAID) or rofecoxib (COX-2 selective NSAID) did not identify any clinically relevant interactions in young healthy Caucasian volunteers.

Phenytoin.

Concomitant administration of 40 mg esomeprazole resulted in a 13% increase in trough plasma levels of phenytoin in epileptic patients. Dose adjustment was not required in this study. It is recommended to monitor the plasma concentrations of phenytoin when treatment with esomeprazole is introduced or withdrawn.

Warfarin.

Concomitant administration of 40 mg esomeprazole to warfarin-treated patients showed that, despite a slight elevation in the trough plasma concentration of the less potent R-isomer of warfarin, the coagulation times were within the accepted range. However, from post-marketing use cases of elevated INR of clinical significance have been reported during concomitant treatment with warfarin. Close monitoring is recommended when initiating and ending treatment with warfarin or other coumarin derivatives.

Tacrolimus.

Concomitant administration of esomeprazole has been reported to increase the serum levels of tacrolimus.

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 esomeprazole may need to be considered.

Antiretroviral drugs.

Concomitant administration with esomeprazole and atazanavir is contraindicated.
Omeprazole has been reported to interact with some antiretroviral drugs. The clinical importance and the mechanisms behind these reported 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 and concomitant administration is not recommended. For other antiretroviral drugs, such as saquinavir, increased serum levels have been reported. There are also some antiretroviral drugs for which unchanged serum levels have been reported when given with omeprazole. Due to the similar pharmacodynamic effects and pharmacokinetic properties of omeprazole and esomeprazole, concomitant administration with esomeprazole and antiretroviral drugs such as nelfinavir is not recommended.

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 esomeprazole (40 mg p.o. daily) resulting in decreased exposure to the active metabolite of clopidogrel by an average of 40%, and resulting in decreased maximum inhibition of (ADP induced) platelet aggregation by an average of 14%. Based on these data, concomitant use of esomeprazole 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.

Medicinal products with pH dependent absorption.

The decreased intragastric acidity during treatment with esomeprazole and other PPIs, might increase or decrease the absorption of drugs if the mechanism of absorption is influenced by gastric acidity. In common with the use of other inhibitors of acid secretion or antacids, the absorption of drugs such as ketoconazole, itraconazole and erlotinib can decrease and the absorption of drugs such as digoxin can increase during treatment with esomeprazole. 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).
Esomeprazole can reduce the absorption of drugs where gastric pH is an important determinant of their bioavailability. Esomeprazole is an enantiomer of omeprazole. Coadministration of omeprazole and mycophenolate mofetil in healthy and transplant patients 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 proton pump inhibitors and mycophenolate mofetil. Use esomeprazole with caution in transplant patients receiving mycophenolate mofetil.

Potential interactions that have been excluded.

Amoxycillin or quinidine.

Esomeprazole has been shown to have no clinically relevant effects on the pharmacokinetics of amoxicillin or quinidine.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

A fertility study has not been conducted on esomeprazole. However, there was no evidence that omeprazole impaired fertility in the rat at an estimated exposure (plasma AUC) of 1-2.5 times the maximum clinical exposure for adults.
(Category B3)
For esomeprazole limited clinical data on exposed pregnancies are available. Esomeprazole should only be given to pregnant women if its use is considered essential.
Esomeprazole was not teratogenic in rats or rabbits at oral doses up to 800 and 250 micromol/kg.day, respectively [corresponding to respective exposures (plasma AUC) of about 6-10 times and 0.04 times the anticipated clinical value in adults]. However, in rabbits, esomeprazole was associated with reduced foetal weights and an increased incidence of minor skeletal anomalies, although these effects were most probably related to the maternal toxicity of esomeprazole in this species. No effects on the foetuses were observed in the rat teratology study, in which an adequate systemic exposure to esomeprazole was achieved.
It is not known if esomeprazole or its metabolites appear in human breast milk. No studies in lactating women have been performed. Therefore esomeprazole should not be used during breast feeding.

4.7 Effects on Ability to Drive and Use Machines

Esomeprazole is not likely to affect the ability to drive or use machines.

4.8 Adverse Effects (Undesirable Effects)

Esomeprazole is well tolerated.

Clinical trials and post-marketing data.

The following adverse reactions have been identified or suspected in the clinical trials program and/or from post-marketing experience for esomeprazole. None was found to be dose-related.
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 system disorders.

Rare: leukopenia, thrombocytopenia.
Very rare: agranulocytosis, pancytopenia.

Immune system disorders.

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

Metabolism and nutrition disorders.

Uncommon: peripheral oedema.
Rare: hyponatraemia.
Very rare: hypomagnesaemia; hypomagnesaemia may result in hypokalaemia and/or hypocalcaemia.

Psychiatric disorders.

Uncommon: insomnia.
Rare: agitation, confusion, depression.
Very rare: aggression, hallucination.

Nervous system disorders.

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

Eye disturbances.

Rare: blurred vision.

Ear and labyrinth disorders.

Uncommon: vertigo.

Respiratory, thoracic, mediastinal disorders.

Rare: bronchospasm.

Gastrointestinal disorders.

Common: abdominal pain, diarrhoea, flatulence, nausea/vomiting, constipation.
Uncommon: dry mouth.
Rare: stomatitis, gastrointestinal candidiasis.
Very rare: microscopic colitis.
Frequency 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.
Very rare: hepatic failure, hepatic encephalopathy.

Skin and subcutaneous tissue disorders.

Uncommon: dermatitis, pruritus, urticaria, rash.
Rare: alopecia, photosensitivity.
Very rare: 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.
Very rare: muscular weakness.

Renal and urinary disorders.

Very rare: tubulointerstitial nephritis (with possible progression to renal failure).

Reproductive system and breast disorders.

Very rare: gynaecomastia.

General disorders and administration site conditions.

Rare: malaise, hyperhidrosis.
See Table 3.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

The symptoms described in connection with deliberate esomeprazole overdose are transient. The symptoms described in connection with 280 mg were gastrointestinal symptoms and weakness. Single doses of 80 mg esomeprazole were uneventful. No specific antidote is known. Esomeprazole is extensively protein bound and is therefore not readily dialyzable. As in any case of overdose, treatment should be symptomatic and general supportive measures should be utilised.
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.

Esomeprazole is a proton pump inhibitor. Esomeprazole magnesium trihydrate reversibly reduces gastric acid secretion by specifically inhibiting the gastric enzyme H+, K+-ATPase proton pump in the parietal cell. Both the R- and S-isomer of omeprazole have similar pharmacodynamic activity. In humans, acid control with esomeprazole is dose dependent and is significantly greater, more sustained and less variable compared to that obtained with equal doses of omeprazole.
Esomeprazole is a weak base and is concentrated and converted to the active form in the highly acidic environment of the secretory canaliculi of the parietal cell, where it inhibits the enzyme H+, K+-ATPase (the acid pump) and inhibits both basal and stimulated acid secretion.

Effect on gastric acid secretion.

After oral dosing with esomeprazole 20 mg and 40 mg the onset of effect occurs within one hour. After repeated administration with 20 mg esomeprazole once daily for five days, mean peak acid output after pentagastrin stimulation is decreased 90% when measured 6-7 hours after dosing on day five.
After five days of oral dosing with 20 mg and 40 mg of esomeprazole, intragastric pH above 4 was maintained for a mean time of 13 hours and 17 hours, respectively over 24 hours in symptomatic GORD patients. The corresponding time for omeprazole 20 mg of 10 hours was significantly shorter. In this study plus another, the percentage of GORD patients maintaining an intragastric pH above 4 for at least 8, 12 and 16 hours are tabulated in Table 4.

In vivo results demonstrate that acid control with esomeprazole is dose dependent and that it is significantly greater, more sustained and less variable compared to an equal dose of the racemate.
Using AUC as a surrogate parameter for plasma concentration, a relationship between inhibition of acid secretion and exposure has been shown.
In separate comparative studies (Table 5) the time and % patients with an intragastric pH above 4 after five days of oral dosing was compared for esomeprazole 40 mg, pantoprazole 40 mg, and lansoprazole 30 mg and rabeprazole 20 mg. The results from these pharmacodynamic studies are tabulated in Table 5.

In a five-way crossover study, the 24 hour intragastric pH profile of oral esomeprazole 40 mg, lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg and rabeprazole 20 mg once daily was evaluated in 34 symptomatic GORD patients. The results are tabulated in Table 6.

A six-way crossover study was conducted to investigate the dose response relationship assessed by intragastric pH monitoring after repeated once daily oral doses of 20, 40 and 80 mg of esomeprazole and 20, 40 and 80 mg of pantoprazole in symptomatic GORD patients. Results are provided in Table 7.

Therapeutic effects of acid inhibition.

Healing of reflux oesophagitis with esomeprazole 40 mg occurs in approximately 78% of patients after four weeks, and in 93% after eight weeks (see Section 5.1 Pharmacodynamic Properties, Clinical trials).
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 and there appears to be a causative link between H. pylori and gastric carcinoma. An attempt to eradicate H. pylori is appropriate therapy in most patients with active or healed peptic ulcer (see Section 5.1 Pharmacodynamic Properties, Clinical trials; Section 4.2 Dose and Method of Administration).
After eradication treatment for one week there is no need for subsequent monotherapy with antisecretory drugs for effective ulcer healing and symptom resolution in uncomplicated duodenal ulcers. Eradication of H. pylori is also associated with long-term remission of peptic ulcer disease, thus reducing complications such as gastrointestinal bleeding, as well as the need for prolonged anti-secretory treatment.

Other effects related to acid inhibition.

During treatment with antisecretory agents serum gastrin increases in response to decreased acid secretion.
An increased number of ECL cells possibly related to the increased serum gastrin levels, have been observed in some patients during long term treatment with esomeprazole.
During long-term treatment with antisecretory drugs gastric glandular cysts have been reported to occur. These changes are a physiological consequence of pronounced inhibition of acid secretion, are benign and appear reversible.

Clinical trials.

Healing of erosive reflux oesophagitis. Randomised double-blind clinical trials (n=15,120) were evaluated to assess the comparative efficacy of esomeprazole in the healing of erosive reflux oesophagitis (grades A to D, according to the Los Angeles endoscopic classification system*) after four and eight weeks treatment. A secondary outcome measure was gastro-oesophageal symptom resolution. These trials compared esomeprazole 40 mg and/or 20 mg with the standard dose of omeprazole 20 mg, lansoprazole 30 mg or pantoprazole 40 mg.

Esomeprazole 40 mg vs esomeprazole 20 mg vs omeprazole 20 mg.

In study B1, the endoscopic healing rates at 4 and 8 weeks and the proportion of patients reporting resolution of symptoms (complete resolution of heartburn and acid regurgitation) were statistically higher for esomeprazole 40 mg compared to omeprazole 20 mg (see Table 8).

Esomeprazole 20 mg vs omeprazole 20 mg.

In study B3, the healing rates were comparable for esomeprazole 20 mg and omeprazole 20 mg (see Table 8).

Based on pooled data from all clinical trials in patients with baseline endoscopy grades B to D, healing rates at 4 and 8 weeks were statistically significantly better for esomeprazole 40 mg, compared with omeprazole 20 mg.

Esomeprazole 40 mg vs lansoprazole 30 mg.

In a randomised, double blind, parallel group trial (n=5,241), the endoscopic healing rates at 4 and 8 weeks were statistically significantly higher for esomeprazole 40 mg compared to lansoprazole 30 mg. Sustained resolution of heartburn occurred faster and in more patients treated with esomeprazole.

Esomeprazole 40 mg vs pantoprazole 40 mg (EXPO study).

In the healing phase of the EXPO study, a randomised, double-blind, multi-centre study (n=3,170), esomeprazole 40 mg had significantly more patients healed on endoscopic assessment at 4 and 8 weeks compared to pantoprazole 40 mg. The proportions of patients with complete healing of reflux oesophagitis by week 8 as per Kaplan-Meier life table estimates were 95.5% (95% CI, 94.43-96.58%) and 92.0% (95% CI, 90.65-93.41%) respectively for esomeprazole 40 mg dose and pantoprazole 40 mg dose (p=0.0006) (Primary Efficacy). When adjusted for severity of initial oesophagitis using the LA classification system, the proportions of patients healed at 8 weeks were 91.6% (95% CI, 90.1-92.9%) and 88.9% (95% CI, 87.3-90.4%) respectively for esomeprazole 40 mg dose and pantoprazole 40 mg dose (p=0.018) (Secondary Efficacy). The crude healing rates after 4 and 8 weeks are given together with the percentages of healed patients for each baseline LA grade in Table 9. Sustained heartburn resolution was achieved significantly faster in patients treated with esomeprazole. The proportion of heartburn-free days was also significantly greater in esomeprazole patients. Endoscopically healed patients free of moderate/severe heartburn and acid regurgitation at 4 or 8 weeks entered the 6 month maintenance phase of the study (see Section 5.1 Pharmacodynamic Properties, Clinical trials, Maintenance treatment of erosive reflux oesophagitis).

Maintenance treatment of erosive reflux oesophagitis. Two randomised double-blind placebo controlled clinical trials (n=750) were evaluated to assess the comparative efficacy of esomeprazole in patients with healed erosive reflux oesophagitis at 1, 2 and 6 months treatment comparing esomeprazole 40 mg or esomeprazole 20 mg or esomeprazole 10 mg with placebo.
Across both studies, maintenance of healing of erosive reflux oesophagitis at 6 months was achieved in a dose-dependent pattern and these results were significantly different from placebo. There were no differences between the esomeprazole 20 mg and 40 mg group of patients.
In the maintenance phase of the EXPO study, endoscopic and symptomatic remission rates in patients with endoscopically healed erosive oesophagitis (n=2,766) were compared in treatment groups receiving either esomeprazole 20 mg or pantoprazole 20 mg once daily for 6 months. Patients were randomised to receive maintenance treatment independent of the treatment used in the healing phase. A significantly higher proportion of patients were in endoscopic and symptomatic remission during 6 months of treatment with esomeprazole 20 mg daily (87.0% [95% CI, 85.1-88.9%] at six months) compared to pantoprazole 20 mg daily (74.9% [95% CI, 72.5-77.3%] at six months) (p-value < 0.0001) as per cumulative life table estimates (Primary Efficacy). The proportion of patients in remission at 6 months, when adjusted for severity of initial oesophagitis using the LA classification system, receiving esomeprazole for the healing and maintenance phase was 70.9% compared to 59.6% of patients receiving pantoprazole for the healing and maintenance phases (p-value < 0.0001) as per Table 10.

Symptomatic treatment of GORD in patients with normal endoscopy. At the time of registration, five randomised, double-blind controlled clinical trials (n=3,362) were evaluated to assess the efficacy of esomeprazole in the complete resolution of heartburn at 4 weeks comparing esomeprazole 20 mg or 40 mg with omeprazole 20 mg or placebo. Study B7 was a dose-finding study, two studies compared esomeprazole 40 mg and omeprazole 20 mg (B8 and B9), and two compared esomeprazole 20 mg, 40 mg and placebo (B16 and B17).
There were no apparent differences in any of the studies between population subsets based on gender, age, race or H. pylori status in the proportion of patients with complete resolution of heartburn by treatment. The proportion of patients with complete resolution of heartburn at 4 weeks in studies B7, B8 and B9 (n=2,645), independent of treatment, was approximately 60%. There was no statistically significant difference between any of the treatment groups with regard to complete resolution of heartburn at 2 weeks or 4 weeks.
In studies B16 and B17 the proportion of patients (n=717) with complete resolution of heartburn at 4 weeks was significantly higher for esomeprazole 20 mg and 40 mg compared to placebo.
Treatment of GORD in paediatric and adolescent patients (1-18 years). A randomised, double-blind multi-centre study was conducted to determine the safety and efficacy in patients with clinically diagnosed GORD aged 12 to 17 years, inclusive (n=149) treated with esomeprazole 20 mg or 40 mg daily. This study was primarily designed as a safety study with a secondary objective to evaluate the clinical outcome. Both doses of esomeprazole were safe and well tolerated with the adverse event profile of this population being consistent with the adverse event profile seen in adults. No clinically important findings or trends in haematology, clinical chemistry, vital signs or physical examination were observed. GORD symptoms were statistically significantly reduced after treatment with esomeprazole.
Symptoms (heartburn, acid regurgitation, epigastric pain, vomiting) were reduced or resolved in both the 20 mg (72.4%) and 40 mg (75.3%) treatment arms over the 8 week study period.
A multi-centre, parallel-group study was conducted in 109 paediatric patients aged 1 to 11 years with endoscopically proven GORD to evaluate safety and tolerability of esomeprazole once daily for up to eight weeks. Dosing of patients was based on weight with patients weighing < 20 kg receiving esomeprazole 5 mg or 10 mg once daily and patients weighing ≥ 20 kg receiving esomeprazole 10 mg or 20 mg once daily. Fifty-three patients had erosive esophagitis at baseline. Of the 45 patients who had follow-up endoscopy, 40 (88.9%) of these patients had their erosive oesophagitis healed through eight weeks. A statistically significant reduction in overall GORD symptom scores from baseline to the final visit, as assessed by the physician/investigators, was observed in all treatment groups. In addition a statistically significant reduction in symptoms from baseline was observed at each study visit (Week 2, Week 4, Week 6, and final visit) for all treatment groups (p < 0.0036). Adverse reactions recorded during the study did not identify any new safety concerns.
On demand treatment. Three large randomised long-term placebo controlled double-blind clinical trials in patients with non-erosive GORD were evaluated to assess the efficacy of on-demand treatment with esomeprazole 20 mg and/or 40 mg or placebo over a 6 month period following initial complete resolution of heartburn.
Based on the primary variable of "time to study discontinuation due to unwillingness to continue" there was no difference between esomeprazole 20 mg and 40 mg. Following initial treatment, effective symptom control is maintained in approximately 90% of patients taking on demand therapy with either esomeprazole 20 mg or 40 mg once daily, when needed. On average, patients only took one dose of esomeprazole approximately every 3 days to effectively control their symptoms, and most patients took esomeprazole for 3 consecutive days or less.
Short-term treatment of NSAID associated upper gastrointestinal (GI) symptoms. Two large randomised multicentre placebo controlled double-blind trials (NEN-0001; n=402 and NEN-0003; n=376) were evaluated to assess the efficacy of esomeprazole 20 mg orally versus placebo through 4 weeks of treatment of upper GI symptoms associated with NSAID use in patients receiving daily NSAID (non-selective and COX-2 selective) therapy.
The primary endpoint for both trials was change in severity of upper GI symptoms associated with NSAID use (pain, discomfort, or burning in the upper abdomen) referred to as upper GI symptoms. Patients completed a diary card once daily during the study period and were instructed to fill in the diary card at the same time each day throughout the study, close to intake of study drug. The patient was asked to rate the intensity of his/her upper GI symptoms by the following question: "How severe has your most intense episode of pain, discomfort or burning in the upper abdomen been during the last 24 hours?" The question was answered using a 7-graded scale as follows: 0=None (No symptoms); 1=Minimal (Can be easily ignored without effort); 2=Mild (Can be ignored with effort); 3=Moderate (Cannot be ignored but does not influence my daily activities); 4=Moderately Severe (Cannot be ignored and occasionally limits my daily activities); 5=Severe (Cannot be ignored and often limits my daily activities); 6=Very Severe (Cannot be ignored and markedly limits my daily activities and often requires rest). Additional symptoms (heartburn, acid regurgitation, and abdominal bloating, and nausea) were captured by investigator-recorded assessments and were considered to be supportive of the primary study endpoint.
A further analysis was performed for; age; gender; race; H. pylori status; NSAID compliance and baseline NSAID type. Validated patient-reported outcome (PRO) measures (including a disease-specific health related quality-of-life questionnaire Gastrointestinal Symptom Rating Scale (GSRS) and the Quality of Life in Reflux and Dyspepsia (QOLRAD)) were also selected as secondary endpoints.
In both trials, esomeprazole was significantly better than placebo in the treatment of upper GI symptoms (pain, discomfort and burning in the upper abdomen) in patients using non-selective or COX-2-selective NSAIDs (see Table 11). These differences were evident at 2 weeks and were sustained or further improved after 4 weeks of treatment. The median time for patients to achieve relief of upper GI symptoms for esomeprazole 20 mg was 10 to 11 days compared to 17 to 21 days for placebo, across both trials. The esomeprazole 20 mg group gained a significantly higher percentage of symptom-free days (range 29.0% to 30.6% of days) compared to placebo (range 13.9% to 21.0% of days) and gained significantly better resolution of investigator-recorded symptoms of heartburn and acid regurgitation compared to placebo.

Based on the Quality of Life in Reflux and Dyspepsia questionnaire, patients on esomeprazole 20 mg gained significantly improved well-being (emotional distress dimension), sleep quality (sleep problem dimension) and improved ability to eat and drink (food/drink problems dimension) compared to placebo. The GSRS questionnaire indicated significantly less reflux symptoms in both studies and significantly less abdominal pain and indigestion in one of the two studies.
No dosage adjustment is required based on age category, gender, race, or type of NSAID. Efficacy parameters were not affected by H. pylori status.
Gastric ulcer healing. Two large randomised, multicentre, active-controlled, comparative, double-blind, parallel-group trials were conducted to assess the efficacy of esomeprazole 40 mg and 20 mg once daily versus ranitidine 150 mg twice daily through 8 weeks of treatment for healing of gastric ulcers in patients receiving daily NSAID (non-selective and COX-2 selective) therapy. Patients had at least one gastric ulcer of ≥ 5 mm but not > 25 mm at greatest diameter. The primary variable was the gastric healing status (healed or unhealed) as observed endoscopically through 8 weeks.
A total of 846 patients were randomised (SH-NEN-0005 n=406; SH-NEN-0006 n=440); 765 patients completed the studies.
In SH-NEN-0005, the efficacy evaluation based on the ITT population (n=399) demonstrated that esomeprazole 40 mg and esomeprazole 20 mg treatment resulted in statistically significant higher observed gastric ulcer healing rates at both Week 4 (E40 p=0.036, E20 p=0.023) and Week 8 (E40 p = < 0.001, E20 p=0.003) compared to the ranitidine 150 mg twice daily treatment. The Week 8 results in the PP population (n=301) were similar to those in the ITT population. In addition, esomeprazole treatment resulted in a statistically significant greater beneficial effect on some patient-reported and investigator-assessed NSAID-associated upper GI symptoms compared to ranitidine following 8 weeks of treatment.
In SH-NEN-0006, the efficacy evaluation based on the ITT population (n=410) demonstrated that esomeprazole 40 mg and esomeprazole 20 mg treatment resulted in statistically significant higher observed gastric ulcer healing rates at Week 4 compared to the ranitidine 150 mg twice daily treatment (E40 p=0.009, E20 p=0.003). At week 8, although not statistically different, the healing rates were numerically higher with esomeprazole 40 mg and esomeprazole 20 mg compared to ranitidine 150 mg twice daily. The Week 4 and Week 8 results in the PP population were similar to those in the ITT population.
Ulcer prevention. Two large randomised, multicentre, placebo-controlled, double-blind, parallel-group studies were conducted to assess the efficacy of up to 6 months of treatment with esomeprazole 40 mg and 20 mg once daily versus placebo in preventing gastric ulcers and/or duodenal ulcers in patients receiving continuous NSAID (non-selective and COX-2 selective) therapy, who were at risk of developing NSAID related ulcers.
A total of 1429 patients were randomised (SH-NEN-0013 n=585; SH-NEN-0014 n=844); 1067 patients completed the studies.
Patients enrolled in the studies were ulcer free (as determined by endoscopy at baseline; erosions were permitted) but at risk of developing NSAID-associated gastric ulcers and/or duodenal ulcers because of a documented gastric and duodenal ulcer within the past 5 years and/or age ≥ 60 years.
The cumulative proportion of patients without gastric ulcer and/or duodenal ulcer throughout the 6 month treatment period was higher in patients treated with esomeprazole 40 mg or esomeprazole 20 mg than in patients treated with placebo. The reduction of gastric ulcer and/or duodenal ulcer development relative to placebo was statistically significant in the 2 studies, both in the ITT and PP population.
A 26-week randomised double-blind, placebo-controlled trial (n=992) was conducted to evaluate the efficacy of esomeprazole 20 mg daily for the prevention of gastric and/or duodenal ulcers in patients taking low-dose aspirin (75-325 mg daily) at moderate to high risk of developing gastroduodenal ulcers. In patients receiving esomeprazole 20 mg the estimated cumulative proportion of patients with a gastric and/or duodenal ulcer at 6 months was significantly lower compared to the placebo group (1.8% vs 6.2%, p=0.0007, life-table analysis).
Esomeprazole 20 mg daily was also significantly more effective at reducing the risk of lesions in the oesophagus compared to placebo in patients using low dose aspirin.
Prevention of rebleeding of gastric or duodenal ulcers. In a randomised, double blind, placebo-controlled clinical study, 764 patients with bleeding gastric or duodenal ulcers were randomised to receive esomeprazole IV for injection (n=375) or placebo (n=389). Following endoscopic haemostasis, patients received either 80 mg esomeprazole IV administered as a bolus infusion over 30 minutes followed by a continuous infusion of 8 mg per hour or placebo for 72 hours. After the initial 72 hour period, all patients received oral esomeprazole 40 mg for 27 days for acid suppression. The occurrence of rebleeding within 3 days was 5.9% in the esomeprazole IV treated group compared to 10.3% for the placebo group. At 7 and 30 days post-treatment, the occurrence of rebleeding in the esomeprazole treated group versus the placebo treated group was 7.2% vs 12.9% and 7.7% vs 13.6% respectively.
The Kaplan-Meier curve in Figure 1 shows the cumulative percentage of patients rebleeding within 30 days of commencing treatment.

Esomeprazole IV treatment followed by the oral treatment regimen reduced the total number of days patients were hospitalised due to rebleeding during the 30 day treatment by 43% compared to placebo. Hospitalisations exceeding 5 days were observed in 4.8% of patients treated with esomeprazole compared to 10.5% for placebo.
Control of gastric acid secretion in patients with hypersecretory states. A 12 month study in 21 patients diagnosed with pathological hypersecretory conditions including Zollinger-Ellison syndrome and idiopathic hypersecretion was conducted to determine if appropriately titrated doses of esomeprazole controlled gastric acid secretion (pharmacodynamic assessment) during the study and to evaluate the safety and tolerability of esomeprazole in patients with hypersecretory states. Basal acid output was controlled with high-dose esomeprazole (doses from 40 mg bid up to 240 mg daily) in 95% (20) of patients at 6 months and 90% (19) at 12 months. Most patients achieved control on 40 mg bid. High-dose esomeprazole was found to be generally safe and well tolerated throughout the study.
Helicobacter pylori eradication. Two large randomised double-blind clinical trials were evaluated to assess the efficacy of esomeprazole in combination with specified antibiotics for the eradication of H. pylori. In the first trial, study B13, the seven day regimen consisted of esomeprazole 20 mg bid in combination with amoxycillin, 1000 mg bid and clarithromycin 250 mg x 2 bid (EAC) and was compared with standard seven day therapy of omeprazole 20 mg bid, amoxycillin 1000 mg bid and clarithromycin 250 mg x 2 bid (OAC). In the second trial, study B14, the above seven day treatment regimen was combined with three additional weeks of treatment with placebo (EAC + placebo) or omeprazole (OAC + omeprazole). This study looked at the healing rate of duodenal ulcer and eradication rate of H. pylori following treatment with omeprazole or placebo.
The estimated intention to treat (ITT) eradication rates in study B13 for the EAC and OAC treatment groups were 90% and 88% respectively. In study B14 the estimated ITT cumulative healing rates were 97% and 96% in the EAC + placebo and OAC + omeprazole groups, respectively, whilst the estimated ITT eradication rates were 86% and 88% respectively.

5.2 Pharmacokinetic Properties

Absorption.

Esomeprazole is acid labile and is administered orally as enteric coated pellets in tablets. The enteric coating film, protecting the esomeprazole magnesium trihydrate, dissolves at a pH above 5.5. Hence esomeprazole magnesium trihydrate is not released until the pellets are emptied into the duodenum.
Once esomeprazole magnesium trihydrate dissolves in this near neutral environment, the esomeprazole ion transforms to its neutral form and is absorbed as such. In vivo conversion to the R-isomer is negligible. Absorption is rapid with peak plasma levels of esomeprazole occurring approximately 1 to 2 hours after the dose. The absolute bioavailability is 64% after a single dose of 40 mg and increases to 89% after repeated once-daily administration. For 20 mg esomeprazole the corresponding values are 50% and 68% respectively.
Food intake both delays and decreases the absorption of esomeprazole although this has no significant influence on the effect of esomeprazole on intragastric acidity.

Distribution.

The apparent volume of distribution at steady state in healthy subjects is approximately 0.22 L/kg body weight. Esomeprazole is 97% protein bound.

Metabolism.

Esomeprazole is completely metabolised by the cytochrome P450 system (CYP450). The intrinsic clearance of esomeprazole (S-isomer) is one third of that of the R-isomer, resulting in a higher AUC with less inter-individual variation compared to the racemate. The major part of the metabolism of esomeprazole is dependent on the polymorphic CYP2C19, responsible for the formation of the hydroxy- and desmethyl metabolites of esomeprazole. The remaining part is dependent on another specific isoform, CYP3A4, responsible for the formation of esomeprazole sulphone, the main metabolite in plasma.
The parameters below reflect mainly the pharmacokinetics in individuals with a functional CYP2C19 enzyme, extensive metabolisers.
Total plasma clearance is about 17 L/h after a single dose and about 9 L/h after repeated administration. The plasma elimination half-life is about 1.3 hours after repeated once-daily dosing. The area under the plasma concentration-time curve increases with repeated administration of esomeprazole. 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 esomeprazole and/or its sulphone metabolite. Esomeprazole is completely eliminated from plasma between doses with no tendency for accumulation during once-daily administration.

Excretion.

The major metabolites of esomeprazole have no effect on gastric acid secretion. Almost 80% of an oral dose of esomeprazole is excreted as metabolites in the urine, the remainder in the faeces. Less than 1% of the parent drug is found in urine.

5.3 Preclinical Safety Data

Genotoxicity.

Esomeprazole was negative in a bacterial gene mutation assay. In clastogenicity tests, esomeprazole was positive (as was omeprazole) in an in vitro chromosome aberration test in human lymphocytes. However, two in vivo tests (a mouse micronucleus test and an in vivo chromosome aberration test in rat bone marrow) in the presence of long and high systemic exposure to esomeprazole, showed that esomeprazole was not clastogenic under in vivo conditions. Exposure levels in man are well below those at which clastogenic effects occurred in vitro.

Carcinogenicity.

Preclinical bridging studies between the enantiomer esomeprazole and the racemate (omeprazole) showed that these compounds are pharmacologically and toxicologically similar at equivalent systemic exposure. Thus, the extensive preclinical database for omeprazole is also relevant for the safety assessment of esomeprazole.
No carcinogenicity studies have been conducted on esomeprazole. However, omeprazole (the racemate) produced enterochromaffin-like (ECL) cell hyperplasia and gastric carcinoids in rats. In a 104-week study in rats, carcinoids were observed at doses (on a mg/m² basis) which ranged from 0.4 to 30-fold the maximum clinical dose for adults. However, a no-effect dose level was not determined in female rats. A similar effect was not observed in a 78-week mouse carcinogenicity study with omeprazole. These gastric effects in the rat are believed to be the result of sustained, pronounced hypergastrinaemia secondary to reduced production of gastric acid. Similar effects are elicited by other proton pump inhibitors, H₂-receptor antagonists and by partial fundectomy.

6 Pharmaceutical Particulars

6.1 List of Excipients

The tablets contain the following inactive ingredients: non pareil seeds 40-50 (PI 108808), hyprolose, crospovidone, icing sugar with maize starch (PI 109216), light magnesium oxide, purified talc, macrogol 6000, methacrylic acid - ethyl acrylate copolymer (1:1), glycerol monostearate, polysorbate 80, hypromellose phthalate, microcrystalline cellulose, povidone, pregelatinised maize starch, silicon dioxide, macrogol 400, hypromellose and purified water. The 20 mg tablet contains Opadry complete film coating system 03B84893 Pink (PI 108603) and the 40 mg tablet contains Opadry complete film coating system 03B54193 Pink (PI 108604).

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. Keep bottle tightly closed/airtight.

6.5 Nature and Contents of Container

Esomeprazole GH is available in Al/Al blister pack (PVC/OPA/Al/PVC/Plain/Al foil) or Al/Al blister pack (PVC/OPA/Al/PVC/Peelable child resistance PET/Al foil) of 7, 30, 100's.
75 cc HDPE bottle with 38 mm neck (with induction sealing liner containing molecular sieve desiccant canister) of 30s or 120 cc HDPE bottle pack (with induction sealing liner containing molecular sieve desiccant canister) of 56's.

Note.

All pack sizes may not be marketed.

Australian registration numbers.

Esomeprazole GH 20 mg tablet blister pack: AUST R 307865.
Esomeprazole GH 40 mg tablet blister pack: AUST R 307866.
Esomeprazole GH 20 mg tablet bottle: AUST R 307868.
Esomeprazole GH 40 mg tablet bottle: AUST R 307867.

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

Esomeprazole GH (esomeprazole enteric-coated tablet) is a proton pump inhibitor. The active ingredient in Esomeprazole GH (esomeprazole enteric-coated tablet) is esomeprazole magnesium trihydrate, a substituted benzimidazole. Esomeprazole is the S-isomer of omeprazole. It is optically stable in vivo, with negligible conversion to the R-isomer.

Chemical structure.

The chemical structure of esomeprazole magnesium trihydrate is:

Chemical name: Magnesium bis[5-methoxy-2-[(S)-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl]-1H-benzimidazol-1-ide] trihydrate.
Molecular formula: C₃₄H₃₆N₆O₆S₂Mg.3H₂O.
Molecular weight: 767. 2 (trihydrate).

CAS number.

[217087-09-7].

7 Medicine Schedule (Poisons Standard)

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