Esomeprazole 20mg gastro-resistant tablets

United Kingdom - English - eMC (Electronic Medicines Compendium)

Buy It Now

Active ingredient:
Esomeprazole
Available from:
NorthStar Healthcare Unlimited Company
ATC code:
A02BC05
INN (International Name):
Esomeprazole
Dosage:
20mg
Pharmaceutical form:
Gastro-resistant tablet
Administration route:
Gastroenteral; Oral
Class:
No Controlled Drug Status
Prescription type:
Valid as a prescribable product
Product summary:
BNF: 01030500; GTIN: 05051089990367

What is in this leaflet

What Esomeprazole gastro-resistant tablets are and what they are used for

What you need to know before you take Esomeprazole gastro-resistant tablets

How to take Esomeprazole gastro-resistant tablets

Possible side effects

How to store Esomeprazole gastro-resistant tablets

Contents of the pack and other information

1. What Esomeprazole gastro-resistant tablets are and what they

are used for

Esomeprazole gastro-resistant tablets contain a medicine called esomeprazole. This

belongs to a group of medicines called ‘proton pump inhibitors’. They work by reducing the

amount of acid that your stomach produces.

Esomeprazole gastro-resistant tablets are used to treat the following conditions:

Adults

‘Gastroesophageal reflux disease’ (GERD). 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.

Ulcers in the stomach or upper part of the gut (intestine) that are infected with

bacteria called ‘Helicobacter pylori’. If you have this condition, your doctor may also

prescribe antibiotics to treat the infection and allow the ulcer to heal.

Stomach ulcers caused by medicines called NSAIDs (Non-Steroidal Anti-Inflammatory

Drugs). Esomeprazole gastro-resistant tablets can also be used to stop stomach

ulcers from forming if you are taking NSAIDs.

Too much acid in the stomach caused by a growth in the pancreas (Zollinger-Ellison

syndrome).

Prolonged treatment after prevention of rebleeding of ulcers with intravenous

esomeprazole.

Adolescents aged 12 years and above

‘Gastroesophageal reflux disease’ (GERD). 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.

Ulcers in the stomach or upper part of the gut (intestine) that are infected with

bacteria called ‘Helicobacter pylori’. If you have this condition, your doctor may also

prescribe antibiotics to treat the infection and allow the ulcer to heal.

2. What you need to know before you take Esomeprazole gastro-

resistant tablets

Do not take Esomeprazole gastro-resistant tablets if:

You are allergic (hypersensitive) to esomeprazole or any of the other ingredients of

this medicine (listed in section 6).

You are allergic to other proton pump inhibitor medicines (e.g. pantoprazole,

lanzoprazole, rabeprazole, omeprazole).

You are taking a medicine containing nelfinavir (used to treat HIV infection).

Do not take Esomeprazole gastro-resistant tablets if any of the above apply to you. If you

are not sure, talk to your doctor or pharmacist before taking Esomeprazole gastro-

resistant tablets.

Warnings and precautions

Talk to your doctor or pharmacist before taking Esomeprazole gastro-resistant tablets if:

You have severe liver problems.

You have severe kidney problems.

You have ever had a skin reaction after treatment with a medicine similar to

Esomeprazole gastro-resistant tablets.

Esomeprazole gastro-resistant tablets may hide the symptoms of other diseases.

Therefore, if any of the following happen to you before you start taking

Esomeprazole gastro-resistant tablets or while you are taking it, talk to your doctor

straight away:

You lose a lot of weight for no reason and have problems swallowing.

You get stomach pain or indigestion.

You begin to vomit food or blood.

You pass black stools (blood-stained faeces).

If you have been prescribed Esomeprazole gastro-resistant tablets “on demand” you

should contact your doctor if your symptoms continue or change in character.

If you get a rash on your skin, especially in the areas exposed to the sun tell your doctor

as soon as you can, as you may need to stop your treatment with Esomeprazole gastro-

resistant tablets. Remember to also mention any other ill-effects like pain in your joints.

Taking a proton pump inhibitor like Esomeprazole gastro-resistant tablets, especially over

a period of more than one year, may slightly increase your risk of fracture in the hip, wrist

or spine. Tell your doctor if you have osteoporosis or if you are taking corticosteroids

(which can increase the risk of osteoporosis).

Children under the age of 12 years

Esomeprazole gastro-resistant tablets should not be used in children younger than 12

years. More appropriate pharmaceutical forms of esomeprazole may be available.

Other medicines and Esomeprazole gastro-resistant tablets

Tell your doctor or pharmacist if you are taking, have recently taken or might take, any

other medicines. This includes medicines that you buy without a prescription. This is

because Esomeprazole gastro-resistant tablets can affect the way some medicines work

and some medicines can have an effect on Esomeprazole gastro-resistant tablets.

DO NOT take Esomeprazole gastro-resistant tablets if you are taking a medicine

containing nelfinavir (used to treat HIV infection).

Tell your doctor or pharmacist if you are taking any of the following medicines:

Atazanavir (used to treat HIV infection).

Clopidogrel (used to prevent blood clots).

Ketoconazole, itraconazole or voriconazole (used to treat infections caused by a

fungus).

Erlotinib (used to treat cancer).

Citalopram, imipramine or clomipramine (used to treat depression).

Diazepam (used to treat anxiety, relax muscles or in epilepsy).

Phenytoin (used in epilepsy). If you are taking phenytoin, your doctor will need to

monitor you when you start or stop taking Esomeprazole gastro-resistant tablets.

Medicines that are used to thin your blood, such as warfarin. Your doctor may need to

monitor you when you start or stop taking Esomeprazole gastro-resistant tablets.

Cilostazol (used to treat intermittent claudication – a pain in your legs when you walk

which is caused by an insufficient blood supply).

Cisapride (used for indigestion and heartburn).

Digoxin (used for heart problems).

Methotrexate (a chemotherapy medicine used in high doses to treat cancer) – if you

are taking a high dose of methotrexate, your doctor may temporarily stop your

esomeprazole treatment.

Tacrolimus (organ transplantation).

Rifampicin (used for treatment of tuberculosis).

St. John’s wort (Hypericum perforatum) (used to treat depression).

If your doctor has prescribed the antibiotics amoxicillin and clarithromycin as well as

Esomeprazole gastro-resistant tablets to treat ulcers caused by Helicobacter pylori

infection, it is very important that you tell your doctor about any other medicines you are

taking.

Esomeprazole gastro-resistant tablets with food and drink

You can take your tablets with food or on an empty stomach.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a

baby, ask your doctor or pharmacist for advice before taking this medicine. Your doctor will

decide whether you can take Esomeprazole gastro-resistant tablets during this time.

It is not known if esomeprazole passes into breast milk. Therefore, you should not take

Esomeprazole gastro-resistant tablets if you are breast-feeding.

Driving and using machines

Esomeprazole gastro-resistant tablets are not likely to affect you being able to drive or use

any tools or machines. However, side effects such as dizziness and blurred vision may

uncommonly or rarely occur (see section 4). If affected, you should not drive or use

machines.

Esomeprazole gastro-resistant tablets contain sucrose and lactose

Sucrose and lactose are types of sugar. If you have been told by your doctor that you have

an intolerance to some sugars, talk to your doctor before taking this medicine.

3. How to take Esomeprazole gastro-resistant tablets

Always take this medicine exactly as your doctor or pharmacist has told you. Check with

your doctor or pharmacist if you are not sure.

If you are taking this medicine for a long time, your doctor will want to monitor you

(particularly if you are taking it for more than a year).

If your doctor has told you to take this medicine as and when you need it, tell your

doctor if your symptoms change.

How much to take

Your doctor will tell you how many tablets to take and how long to take them for. This

will depend on your condition, how old you are and how well your liver works.

The recommended doses are given below.

Adults aged 18 and above

To treat heartburn caused by gastroesophageal reflux disease (GERD):

If your doctor has found that your food pipe (gullet) has been slightly damaged, the

recommended dose is one Esomeprazole 40 mg gastro-resistant tablet once a day for

4 weeks. Your doctor may tell you to take the same dose for a further 4 weeks if your

gullet has not yet healed.

The recommended dose once the gullet has healed is one Esomeprazole 20mg

gastro-resistant tablet once a day.

If your gullet has not been damaged, the recommended dose is one Esomeprazole

20mg gastro-resistant tablet each day. Once the condition has been controlled, your

doctor may tell you to take your medicine as and when you need it, up to a maximum

of one Esomeprazole 20mg gastro-resistant tablet each day.

If you have severe liver problems, your doctor may give you a lower dose.

To treat ulcers caused by Helicobacter pylori infection and to stop them coming

back:

The recommended dose is one Esomeprazole 20mg gastro-resistant tablet twice a

day for one week.

Your doctor will also tell you to take antibiotics for example amoxicillin and

clarithromycin.

To treat stomach ulcers caused by NSAIDs (Non-Steroidal Anti-Inflammatory

Drugs):

The recommended dose is one Esomeprazole 20mg gastro-resistant tablet once a

day for 4 to 8 weeks.

To prevent stomach ulcers if you are taking NSAIDs (Non-Steroidal Anti-

Inflammatory Drugs):

The recommended dose is one Esomeprazole 20mg gastro-resistant tablet once a

PACKAGE LEAFLET: INFORMATION FOR THE USER

ESOMEPRAZOLE 20mg and 40mg

GASTRO-RESISTANT TABLETS

Esomeprazole

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or pharmacist.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

day.

To treat too much acid in the stomach caused by a growth in the pancreas

(Zollinger-Ellison syndrome):

The recommended dose is one Esomeprazole 40mg gastro-resistant tablet twice a

day.

Your doctor will adjust the dose depending on your needs and will also decide how

long you need to take the medicine for. The maximum dose is 80mg twice a day.

Prolonged treatment after prevention of rebleeding of ulcers with intravenous

esomeprazole:

The recommended dose is one Esomeprazole 40mg gastro-resistant tablet once a

day for 4 weeks.

Adolescents aged 12 or above

To treat heartburn caused by gastroesophageal reflux disease (GERD):

If your doctor has found that your food pipe (gullet) has been slightly damaged, the

recommended dose is one Esomeprazole 40mg gastro-resistant tablet once a day for

4 weeks. Your doctor may tell you to take the same dose for a further 4 weeks if your

gullet has not yet healed.

The recommended dose once the gullet has healed is one Esomeprazole 20mg

gastro-resistant tablet once a day.

If your gullet has not been damaged, the recommended dose is one Esomeprazole

20mg gastro-resistant tablet each day.

If you have severe liver problems, your doctor may give you a lower dose.

To treat ulcers caused by Helicobacter pylori infection and to stop them coming

back:

The recommended dose is one Esomeprazole 20mg gastro-resistant tablet twice a

day for one week.

Your doctor will also tell you to take antibiotics for example amoxicillin and

clarithromycin.

Taking this medicine

You can take your tablets at any time of the day.

You can take your tablets with food or on an empty stomach.

Swallow your tablets whole with a drink of water. DO NOT chew or crush the tablets.

This is because the tablets contain coated pellets which stop the medicine from being

broken down by the acid in your stomach. It is important not to damage the pellets.

What to do if you have trouble swallowing the tablets

If you have trouble swallowing the tablets:

Put them into a glass of still (non-fizzy) water. Do not use any other liquids.

Stir until the tablets break up (the mixture will not be clear). Then drink the mixture

straight away or within 30 minutes. Always stir the mixture just before drinking it.

To make sure that you have drunk all of the medicine, rinse the glass very well

with half a glass of water and drink it. The solid pieces contain the medicine - do

not chew or crush them.

If you cannot swallow at all, the tablet can be mixed with some water and put into a

syringe. It can then be given to you through a tube directly into your stomach (‘gastric

tube’).

Children under the age of 12 years

Esomeprazole gastro-resistant tablets are not recommended for children less than 12

years old.

Older people

Dose adjustment is not required in the elderly.

If you take more Esomeprazole gastro-resistant tablets than you should

If you take more Esomeprazole gastro-resistant tablets than prescribed by your doctor,

talk to your doctor or pharmacist STRAIGHT AWAY.

If you forget to take Esomeprazole gastro-resistant tablets

If you forget to take a dose, take it as soon as you remember it. However, if it is almost

time for your next dose, skip the missed dose.

DO NOT take a double dose (two doses at the same time) to make up for a forgotten

dose.

If you have any further questions on the use of this medicine, ask your doctor or

pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets

them.

If you notice any of the following serious side effects, stop taking Esomeprazole

gastro-resistant tablets and contact a doctor IMMEDIATELY:

Sudden wheezing, swelling of your lips, tongue and throat or body, rash, fainting or

difficulties in swallowing (severe allergic reaction).

Reddening of the skin with blisters or peeling. There may also be severe blisters and

bleeding in the lips, eyes, mouth, nose and genitals. This could be ‘Stevens-Johnson

syndrome’ or ‘toxic epidermal necrolysis’.

Yellow skin, dark urine and tiredness which can be symptoms of liver problems.

These effects are rare and may affect up to 1 in 1000 people.

Other side effects include:

Common (may affect up to 1 in 10 people)

Headache.

Effects on your stomach or gut: diarrhoea, stomach pain, constipation, wind

(flatulence).

Feeling sick (nausea) or being sick (vomiting).

Benign polyps in the stomach.

Uncommon (may affect up to 1 in 100 people)

Swelling of the feet and ankles.

Disturbed sleep (insomnia).

Dizziness, tingling feelings such as “pins and needles”, feeling sleepy.

Spinning feeling (vertigo).

Dry mouth.

Changes in blood tests that check how the liver is working.

Skin rash, lumpy rash (hives) and itchy skin.

Fracture of the hip, wrist or spine (if Esomeprazole gastro-resistant tablets are used in

high doses and over long duration).

Rare (may affect up to 1 in 1000 people)

Blood problems such as a reduced number of white cells or platelets. This can cause

weakness, bruising or make infections more likely.

Low levels of sodium in the blood. This may cause weakness, being sick (vomiting)

and cramps.

Feeling agitated, confused or depressed.

Taste changes.

Eyesight problems such as blurred vision.

Suddenly feeling wheezy or short of breath (bronchospasm).

An inflammation of the inside of the mouth.

An infection called “thrush” which can affect the gut and is caused by a fungus.

Liver problems, including jaundice which can cause yellow skin, dark urine, and

tiredness.

Hair loss (alopecia).

Skin rash on exposure to sunshine.

Joint pains (arthralgia) or muscle pains (myalgia).

Generally feeling unwell and lacking energy.

Increased sweating.

Very rare (may affect up to 1 in 10000 people)

Changes in blood count including agranulocytosis (lack of white blood cells).

Aggression.

Seeing, feeling or hearing things that are not there (hallucinations).

Severe liver problems leading to liver failure and inflammation of the brain.

Sudden onset of a severe rash or blistering or peeling skin. This may be associated

with a high fever and joint pains (Erythema multiforme, Stevens-Johnson syndrome,

toxic epidermal necrolysis).

Muscle weakness.

Severe kidney problems.

Enlarged breasts in men.

Not known (frequency cannot be estimated from the available data)

If you are on Esomeprazole gastro-resistant tablets for more than three months it is

possible that the levels of magnesium in your blood may fall. Low levels of magnesium

can be seen as fatigue, involuntary muscle contractions, disorientation, convulsions,

dizziness or increased heart rate. If you get any of these symptoms, please tell your

doctor promptly. Low levels of magnesium can also lead to a reduction in potassium or

calcium levels in the blood. Your doctor may decide to perform regular blood tests to

monitor your levels of magnesium.

Inflammation in the gut (leading to diarrhoea).

Rash, possibly with pain in the joints.

Esomeprazole gastro-resistant tablets may in very rare cases affect the white blood cells

leading to immune deficiency. If you have an infection with symptoms such as fever with a

severely reduced general condition or fever with symptoms of a local infection such as

pain in the neck, throat or mouth or difficulties in urinating, you must consult your doctor

as soon as possible so that a lack of white blood cells (agranulocytosis) can be ruled out

by a blood test. It is important for you to give information about your medication at this

time.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any

possible side effects not listed in this leaflet. You can also report side effects directly via

the Yellow Card Scheme (website: www.mhra.gov.uk/yellowcard) or search for MHRA

Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help

provide more information on the safety of this medicine.

5. How to store Esomeprazole gastro-resistant tablets

Keep this medicine out of the sight and reach of children.

Store below 25°C.

Keep this medicine in the original package or keep the bottle tightly closed to protect

from moisture.

Do not use this medicine after the expiry date which is stated on the blister, bottle and

carton after EXP. The expiry date refers to the last day of that month.

Do not throw away any medicines via wastewater or household waste. Ask your

pharmacist how to throw away medicines you no longer use. These measures will help

to protect the environment.

6. Contents of the pack and other information

What Esomeprazole gastro-resistant tablets contains

The active substance is esomeprazole. Esomeprazole gastro-resistant tablets come in two

strengths containing 20mg or 40mg of esomeprazole (as magnesium salt).

The other ingredients are sucrose, maize starch, hydroxypropylcellulose (E463),

crospovidone (E1202), hydroxypropyl methylcellulose (E464), magnesium oxide, talc

(E553b), macrogol, polysorbate 80 (E433), glycerol monostearate (E471), methacrylic

acid ethyl acrylate copolymer dispersion 30 percent, hypromellose phthalate,

microcrystalline cellulose (E460), ferric oxide red (E172), ferric oxide yellow (E172) (only

for the 20mg), povidone (E1201), pregelatinized starch, colloidal hydrated silica, titanium

dioxide (E171), lactose monohydrate.

What Esomeprazole gastro-resistant tablets look like and contents of the pack

Esomeprazole 20mg gastro-resistant tablets are light pink coloured, oblong, biconvex,

coated tablets debossed with 20 on one side and CE on the other.

Esomeprazole 40mg gastro-resistant tablets are pink coloured, oblong, biconvex,

coated tablets debossed with 40 on one side and CE on the other.

Your tablets will come in bottles or blister packs of 28 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Crescent Pharma Limited,

Units 3 & 4, Quidhampton Business Units,

Polhampton Lane, Overton,

Hampshire RG25 3ED

United Kingdom

Manufacturer

PSI supply nv

Axxes Business Park

Guldensporenpark 22 – Block C

9820 Merelbeke

Belgium

PharmaS d.o.o.

Industrijska cesta 5

Potok

Popova

a, 44317

Croatia

This leaflet was last revised in 05/2018.

Barcode

Pharmacode

SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT

Esomeprazole 20mg Gastro-resistant Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

One gastro-resistant tablet contains 20mg of esomeprazole (corresponding to

21.75mg esomeprazole magnesium dihydrate).

Excipient with known effect:

Each tablet contains no more than 5.65 mg of sucrose.

For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM

Gastro-resistant tablet.

20mg: A light pink, elliptically shaped, biconvex film-coated tablet, 6.55 x 13.6 mm.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

Adults

Esomeprazole 20mg tablets are indicated in adults 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)

In combination with appropriate antibacterial therapeutic regimens for the eradication

of Helicobacter pylori and

healing of Helicobacter pylori associated duodenal ulcer and

prevention of relapse of peptic ulcers in patients with Helicobacter pylori

associated ulcers

Patients requiring continued NSAID therapy

- healing of gastric ulcers associated with NSAID therapy.

prevention of gastric and duodenal ulcers associated with NSAID therapy, in

patients at risk.

Treatment of Zollinger Ellison Syndrome

Esomeprazole 20mg tablets are indicated in adolescents from the age of 12 years 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)

In combination with antibiotics in treatment of duodenal ulcer caused by

Helicobacter pylori

4.2

Posology and method of administration

Posology

Adults

Gastro-oesophageal Reflux Disease (GORD)

treatment of erosive reflux oesophagitis

40mg esomeprazole 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 of patients with healed oesophagitis to prevent

relapse

20mg esomeprazole once daily.

symptomatic treatment of gastro-oesophageal reflux disease (GORD)

20mg esomeprazole once daily in patients without oesophagitis. 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 20mg

esomeprazole once daily. An on demand regimen taking 20mg esomeprazole once

daily, when needed, can be used. In NSAID treated patients at risk of developing

gastric and duodenal ulcers, subsequent symptom control using an on demand

regimen is not recommended.

In combination with appropriate antibacterial therapeutic regimens for the eradication

of Helicobacter pylori and

-

healing of Helicobacter pylori associated duodenal ulcer and

-

prevention of relapse of peptic ulcers in patients with Helicobacter pylori

associated ulcers.

20mg esomeprazole with 1g amoxicillin and 500mg clarithromycin, all twice daily

for 7 days.

Patients requiring continued NSAID therapy

Healing of gastric ulcers associated with NSAID therapy: The usual dose is 20mg

esomeprazole once daily. The treatment duration is 4-8 weeks.

Prevention of gastric and duodenal ulcers associated with NSAID therapy in patients

at risk: 20mg esomeprazole once daily.

Treatment of Zollinger Ellison Syndrome

The recommended initial dosage is 40mg esomeprazole twice daily. The dosage

should then be individually adjusted and treatment continued as long as clinically

indicated. Based on the clinical data available, the majority of patients can be

controlled on doses between 80 to 160 mg esomeprazole daily. With doses above

80mg daily, the dose should be divided and given twice daily.

Special populations

Patients with impaired renal function

Dose 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 (see section 5.2).

Patients with impaired hepatic function

Dose adjustment is not required in patients with mild to moderate liver impairment.

For patients with severe liver impairment, a maximum dose of 20 mg esomeprazole

should not be exceeded (see section 5.2).

Elderly

Dose adjustment is not required in the elderly.

Paediatric population

Adolescents from the age of 12 years

Gastro-oesophageal Reflux Disease (GORD)

treatment of erosive reflux oesophagitis

40 mg esomeprazole 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 of patients with healed oesophagitis to prevent relapse

20 mg esomeprazole once daily.

-symptomatic treatment of gastro-oesophageal reflux disease (GORD)

20 mg esomeprazole once daily in patients without oesophagitis. 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

esomeprazole once daily.

Treatment of duodenal ulcer caused by Helicobacter 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.

The posology recommendation is:

Weight

Posology

30 - 40 kg

Combination with two antibiotics: esomeprazole 20mg, amoxicillin

750mg and clarithromycin 7.5mg/kg body weight are all administered

together twice daily for one week.

> 40 kg

Combination with two antibiotics: esomeprazole 20mg, amoxicillin 1 g

and clarithromycin 500mg are all administered together twice daily for

one week.

Children below the age of 12 years

Esomeprazole should not be used in children younger than 12 years. More

appropriate pharmaceutical forms of esomeprazole may be available.

Method of administration

The tablets should be swallowed whole with liquid. The tablets should not be chewed

or crushed.

For patients who have difficulty in swallowing, the tablets can also be dispersed in

half a glass of non-carbonated water. No other liquids should be used as the enteric

coating may be dissolved. 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 through a gastric tube. It is important that the appropriateness

of the selected syringe and tube is carefully tested. For preparation and

administration instructions see section 6.6.

4.3

Contraindications

Hypersensitivity to the active substance, to substituted benzimidazoles or to any of

the excipients listed in section 6.1.

Esomeprazole should not be used concomitantly with nelfinavir (see section 4.5).

4.4

Special warnings and precautions for use

In 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.

Long term use

Patients on long-term treatment (particularly those treated for more than a year)

should be kept under regular surveillance.

On demand treatment

Patients on on-demand treatment should be instructed to contact their physician if

their symptoms change in character.

Helicobacter pylori eradication

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.

Gastrointestinal infections

Treatment with proton pump inhibitors may lead to slightly increased risk of

gastrointestinal infections such as Salmonella and Campylobacter (see section 5.1).

Absorption of vitamin B12

Esomeprazole, as all acid-blocking medicines, may reduce the absorption of

vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be

considered in patients with reduced body stores or risk factors for reduced

vitamin B12 absorption on long-term therapy.

Hypomagnesaemia

Severe hypomagnesaemia has been reported in patients treated with proton pump

inhibitors (PPIs) like esomeprazole for at least three months, and in most cases for a

year. Serious manifestations of hypomagnesaemia such as fatigue, tetany, delirium,

convulsions, dizziness and ventricular arrhythmia can occur but they may begin

insidiously and be overlooked. In most affected patients, hypomagnesaemia

improved after magnesium replacement and discontinuation of the PPI.

For patients expected to be on prolonged treatment or who take PPIs with

digoxin or drugs that may cause hypomagnesaemia (e.g., diuretics), healthcare

professionals should consider measuring magnesium levels before starting PPI

treatment and periodically during treatment.

Risk of fracture

Proton pump inhibitors, especially if used in high doses and over long

durations (> 1 year), may modestly increase the risk of hip, wrist and spine

fracture, predominantly in the elderly or in presence of other recognised risk

factors. Observational studies suggest that proton pump inhibitors may

increase the overall risk of fracture by 10–40 %. Some of this increase may be

due to other risk factors. Patients at risk of osteoporosis should receive care

according to current clinical guidelines and they should have an adequate

intake of vitamin D and calcium.

Subacute cutaneous lupus erythematosus (SCLE)

Proton pump inhibitors are associated with very infrequent cases of SCLE. If lesions

occur, especially in sun-exposed areas of the skin, and if accompanied by arthralgia,

the patient should seek medical help promptly and the health care professional should

consider stopping Esomeprazole. SCLE after previous treatment with a proton pump

inhibitor may increase the risk of SCLE with other proton pump inhibitors

Combination with other medicinal products

Co-administration of esomeprazole with atazanavir is not recommended (see section

4.5). If the combination of atazanavir with a proton pump inhibitor is judged

unavoidable, close clinical monitoring is recommended in combination with an

increase in the dose of atazanavir to 400mg with 100mg of ritonavir; esomeprazole

20mg should not be exceeded.

Esomeprazole is a CYP2C19 inhibitor. When starting or ending treatment with

esomeprazole, the potential for interactions with drugs metabolised through

CYP2C19 should be considered. An interaction is observed between clopidogrel and

esomeprazole (see section 4.5). The clinical relevance of this interaction is uncertain.

As a precaution, concomitant use of esomeprazole and clopidogrel should be

discouraged.

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).

Sucrose

This medicinal product contains sucrose. Patients with rare hereditary problems of

fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase

insufficiency should not take this medicine.

Interference with laboratory tests

Increased Chromogranin A (CgA) level may interfere with investigations for

neuroendocrine tumours. To avoid this interference, esomeprazole treatment

should be stopped for at least five days before CgA measurements (see section

5.1).

4.5

Interaction with other medicinal products and other forms of interaction

Effects of esomeprazole on the pharmacokinetics of other drugs

Protease inhibitors

Omeprazole has been reported to interact with some protease inhibitors. 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 protease inhibitors. Other possible interaction mechanisms are via inhibition of

CYP 2C19.

For atazanavir and nelfinavir, decreased serum levels have been reported

when given together with omeprazole and concomitant administration is not

recommended. Co-administration of omeprazole (40 mg once daily) with

atazanavir 300 mg/ritonavir 100 mg to healthy volunteers resulted in a

substantial reduction in atazanavir exposure (approximately 75% decrease in

AUC, C

Cmin

). Increasing the atazanavir dose to 400 mg did not

compensate for the impact of omeprazole on atazanavir exposure. The

co-administration of omeprazole (20 mg qd) with atazanavir 400 mg/ritonavir

100 mg to healthy volunteers resulted in a decrease of approximately 30% in

the atazanavir exposure as compared with the exposure observed with

atazanavir 300 mg/ritonavir 100 mg qd without omeprazole 20 mg qd.

Co-administration of omeprazole (40 mg qd) reduced mean nelfinavir AUC,

Cmin

by 36-39 % and mean AUC, C

Cmin

for the

pharmacologically active metabolite M8 was reduced by 75-92%. Due to the

similar pharmacodynamic effects and pharmacokinetic properties of

omeprazole and esomeprazole, concomitant administration with esomeprazole

and atazanavir is not recommended (see section 4.4) and concomitant

administration with esomeprazole and nelfinavir is contraindicated (see

section 4.3).

For saquinavir (with concomitant ritonavir), increased serum levels

(80-100%) have been reported during concomitant omeprazole treatment

(40 mg qd). Treatment with omeprazole 20 mg qd had no effect on the

exposure of darunavir (with concomitant ritonavir) and amprenavir (with

concomitant ritonavir). Treatment with esomeprazole 20 mg qd had no effect

on the exposure of amprenavir (with and without concomitant ritonavir).

Treatment with omeprazole 40 mg qd had no effect on the exposure of

lopinavir (with concomitant ritonavir). Methotrexate

When given together with PPIs, methotrexate levels have been reported to

increase in some patients. In high-dose methotrexate administration a

temporary withdrawal of esomeprazole may need to be considered.

Tacrolimus

Concomitant administration of esomeprazole has been reported to increase the

serum levels of tacrolimus. A reinforced monitoring of tacrolimus

concentrations as well as renal function (creatinine clearance) should be

performed, and dosage of tacrolimus adjusted if needed.

Medicinal products with pH dependent absorption

Gastric acid suppression during treatment with esomeprazole and other PPIs

might decrease or increase the absorption of medicinal products with a gastric

pH dependent absorption. As with other medicinal products that decrease

intragastric acidity, the absorption of medicinal products such as

ketoconazole, itraconazole and erlotinib can decrease and the absorption of

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). Digoxin toxicity has been rarely reported. However, caution should

be exercised when esomeprazole is given at high doses in elderly patients.

Therapeutic drug monitoring of digoxin should then be reinforced.

Medicinal products metabolised by CYP2C19

Esomeprazole inhibits CYP2C19, the major esomeprazole metabolising enzyme.

Thus, when esomeprazole is combined with drugs metabolised by CYP2C19, such as

diazepam, citalopram, imipramine, clomipramine, phenytoin etc., 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.

Diazepam

Concomitant administration of 30 mg esomeprazole resulted in a 45% decrease in

clearance of the CYP2C19 substrate diazepam.

Phenytoin

Concomitant administration of 40 mg esomeprazole resulted in a 13% increase in

trough plasma levels of phenytoin in epileptic patients. It is recommended to monitor

the plasma concentrations of phenytoin when treatment with esomeprazole is

introduced or withdrawn.

Voriconazole

Omeprazole (40 mg once daily) increased voriconazole (a CYP2C19 substrate) C

and AUC

by 15% and 41%, respectively.

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

AUC for cilostazol by 18% and 26% respectively, and one of its active metabolites

by 29% and 69% respectively.

CisaprideIn healthy volunteers, concomitant administration of 40 mg esomeprazole

resulted in a 32% increase in area under the plasma concentration-time curve (AUC)

and a 31% prolongation of elimination half-life (t

) 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 also section 4.4).

Warfarin

Concomitant administration of 40 mg esomeprazole to warfarin-treated

patients in a clinical trial showed that coagulation times were within the

accepted range. However, post-marketing, a few isolated cases of elevated

INR of clinical significance have been reported during concomitant treatment.

Monitoring is recommended when initiating and ending concomitant

esomeprazole treatment during treatment with warfarin or other coumarine

derivatives.

Clopidogrel

Results from studies in healthy subjects have shown a pharmacokinetic (PK)/

pharmacodynamic (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 %.

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 the same in the

clopidogrel and the clopidogrel + the combined (esomeprazole + ASA)

product groups.

Inconsistent data on the clinical implications of this PK/PD interaction of

esomeprazole in terms of major cardiovascular events have been reported

from both observational and clinical studies. As a precaution, concomitant use

of clopidogrel should be discouraged.

Investigated medicinal products with no clinically relevant interaction

Amoxicillin and quinidine

Esomeprazole has been shown to have no clinically relevant effects on the

pharmacokinetics of amoxicillin or quinidine.

Naproxen or rofecoxib

Studies evaluating concomitant administration of esomeprazole and either

naproxen or rofecoxib did not identify any clinically relevant pharmacokinetic

interactions during short-term studies.

Effects of other medicinal products on the pharmacokinetics of esomeprazole

Medicinal products which inhibit CYP2C19 and/or CYP3A4

Esomeprazole is metabolised by CYP2C19 and CYP3A4. Concomitant

administration of esomeprazole and a CYP3A4 inhibitor, clarithromycin (500 mg

b.i.d.), resulted in a doubling of the exposure (AUC) to esomeprazole. Concomitant

administration of esomeprazole and a combined inhibitor of CYP2C19 and CYP3A4

may result in more than doubling of the esomeprazole exposure.

The CYP2C19 and CYP3A4 inhibitor voriconazole increased omeprazole AUC

280%. A dose adjustment of esomeprazole is not regularly required in either of these

situations. However, dose adjustment should be considered in patients with severe

hepatic impairment and if long-term treatment is indicated.

Medicinal products which induce CYP2C19 and/or CYP3A4

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.

Paediatric population

Interaction studies have only been performed in adults.

4.6

Fertility, pregnancy and lactation

Pregnancy

Clinical data on exposed pregnancies with esomeprazole are insufficient. With the

racemic mixture, omeprazole, data on a larger number of exposed pregnancies from

epidemiological studies indicate no malformative nor foetotoxic effect. Animal

studies with esomeprazole do not indicate direct or indirect harmful effects with

respect to embryonal/fetal development. Animal studies with the racemic mixture do

not indicate direct or indirect harmful effects with respect to pregnancy, parturition or

postnatal development. Caution should be exercised when prescribing to pregnant

women.

A moderate amount of data on pregnant women (between 300-

1000 pregnancy outcomes) indicates no malformative or foeto/neonatal

toxicity of esomeprazole.

Animal studies do not indicate direct or indirect harmful effects with respect

to reproductive toxicity (see section 5.3).

Breastfeeding

It is not known whether esomeprazole is excreted in human breast milk. There is

insufficient information on the effects of esomeprazole in newborns/infants

Esomeprazole should not be used during breast-feeding.

Fertility

Animal studies with the racemic mixture omeprazole, given by oral

administration do not indicate effects with respect to fertility.

4.7

Effects on ability to drive and use machines

Esomeprazole has minor influence on the ability to drive or use machines. Adverse

reactions such as dizziness (uncommon) and blurred vision (rare) has been reported

(see section 4.8). If affected patients should not drive or use machines

4.8

Undesirable effects

Summary of the safety profile

Headache, abdominal pain, diarrhoea and nausea are among those adverse

reactions that have been most commonly reported in clinical trials (and also

from post-marketing use). In addition, the safety profile is similar for different

formulations, treatment indications, age groups and patient populations. No

dose-related adverse reactions have been identified.

Tabulated list of adverse reactions

The following adverse drug reactions have been identified or suspected in the clinical

trials programme for esomeprazole and post-marketing. None was found to be

dose-related. The reactions are classified according to frequency (very common

1/10; common

1/100 to <1/10; uncommon

1/1,000 to <1/100; rare

1/10,000 to

<1/1,000; very rare <1/10,000; not known (cannot be estimated from the available

data)).

System Organ Class

Frequency

Undesirable Effect

Rare

Leukopenia, thrombocytopenia

Blood and lymphatic

system disorders

Very rare

Agranulocytosis,

pancytopenia

Immune system disorders

Rare

Hypersensitivity reactions e.g.

fever, angioedema and

anaphylactic reaction/shock

Uncommon

Peripheral oedema

Rare

Hyponatraemia

Metabolism and nutrition

disorders

Not known

Hypomagnesaemia (see section

4.4); severe hypomagnesaemia

can correlate with

hypocalcaemia.

Hypomagnesaemia may also be

associated with hypokalaemia

Uncommon

Insomnia

Rare

Agitation, confusion, depression

Psychiatric disorders

Very rare

Aggression, hallucinations

Common

Headache

Uncommon

Dizziness, paraesthesia,

somnolence

Nervous system disorders

Rare

Taste disturbance

Eye disorders

Rare

Blurred vision

Ear and labyrinth

disorders

Uncommon

Vertigo

Respiratory, thoracic and

mediastinal disorders

Rare

Bronchospasm

Common

Abdominal pain, constipation,

diarrhoea, flatulence,

nausea/vomiting, fundic gland

polyps (benign)

Uncommon

Dry mouth

Rare

Stomatitis, gastrointestinal

candidiasis

Gastrointestinal disorders

Not known

Microscopic colitis

Uncommon

Increased liver enzymes

Rare

Hepatitis with or without

jaundice

Hepatobiliary disorders

Very rare

Hepatic failure, encephalopathy

in patients with pre-existing liver

disease

Uncommon

Dermatitis, pruritus, rash,

urticaria

Rare

Alopecia, photosensitivity

Very rare

Erythema multiforme,

Stevens-Johnson syndrome,

toxic epidermal necrolysis

(TEN)

Skin and subcutaneous

tissue disorders

Not known

Subacute cutaneous lupus

erythematosus (see section 4.4)

Uncommon

Fracture of the hip, wrist or

spine (see section 4.4)

Rare

Arthralgia, myalgia

Musculoskeletal and

connective tissue

disorders

Very rare

Muscular weakness

Renal and urinary

disorders

Very rare

Interstitial nephritis, in some

patients renal failure has been

reported concomitantly

Reproductive system and

breast disorders

Very rare

Gynaecomastia

General disorders and

administration site

conditions

Rare

Malaise, increased sweating

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme; website:

www.mhra.gov.uk/yellowcard

4.9

Overdose

There is very limited experience to date with deliberate overdose. 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 plasma 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.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Drugs for acid-related disorders, proton pump inhibitor,

ATC code: A02B C05

Esomeprazole is the S-isomer of omeprazole and reduces gastric acid secretion

through a specific targeted mechanism of action. It is a specific inhibitor of the acid

pump in the parietal cell. Both the R-and S-isomer of omeprazole have similar

pharmacodynamic activity.

Mechanism of action

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

-ATPase – the acid pump and inhibits both basal and

stimulated acid secretion.

Pharmacodynamic effects

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 proportion of patients

maintaining an intragastric pH above 4 for at least 8, 12 and 16 hours respectively

were for esomeprazole 20 mg 76%, 54% and 24%. Corresponding proportions for

esomeprazole 40 mg were 97%, 92% and 56%.

Using AUC as a surrogate parameter for plasma concentration, a relationship

between inhibition of acid secretion and exposure has been shown.

Healing of reflux oesophagitis with esomeprazole 40 mg occurs in approximately

78% of patients after four weeks, and in 93% after eight weeks.

One week treatment with esomeprazole 20 mg b.i.d. and appropriate antibiotics,

results in successful eradication of H. pylori in approximately 90% of patients.

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.

In a randomized, double blind, placebo-controlled clinical study, patients with

endoscopically confirmed peptic ulcer bleeding characterised as Forrest Ia, Ib, IIa or

IIb (9%, 43%, 38% and 10 % respectively) were randomized to receive esomeprazole

solution for infusion (n=375) or placebo (n=389). Following endoscopic hemostasis,

patients received either 80 mg esomeprazole as an intravenous 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 open-label 40 mg oral

esomeprazole for 27 days for acid suppression. The occurrence of rebleeding within

3 days was 5.9% in the esomeprazole treated group compared to 10.3% for the

placebo group. At 30 days post-treatment, the occurrence of rebleeding in the

esomeprazole treated versus the placebo treated group 7.7% vs 13.6%.

During treatment with antisecretory medicinal products serum gastrin

increases in response to the decreased acid secretion. Also CgA increases due

to decreased gastric acidity. The increased CgA level may interfere with

investigations for neuroendocrine tumours. Available published evidence

suggests that proton pump inhibitors should be discontinued between 5 days

and 2 weeks prior to CgA measurements. This is to allow CgA levels that

might be spuriously elevated following PPI treatment to return to reference

range.

An increased number of ECL cells possibly related to the increased serum

gastrin levels, have been observed in both children and adults during long

term treatment with esomeprazole. The findings are considered to be of no

clinical significance.

During long-term treatment with antisecretory drugs gastric glandular cysts have

been reported to occur at a somewhat increased frequency. These changes are a

physiological consequence of pronounced inhibition of acid secretion, are benign and

appear to be reversible.

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.

Clinical efficacy

In two studies with ranitidine as an active comparator, esomeprazole showed better

effect in healing of gastric ulcers in patients using NSAIDs, including COX-2

selective NSAIDs.

In two studies with placebo as comparator, esomeprazole showed better effect in the

prevention of gastric and duodenal ulcers in patients using NSAIDs (aged >60 and/or

with previous ulcer), including COX-2 selective NSAIDs.

Paediatric population

In a study in paediatric GORD patients (<1 to 17 years of age) receiving long-term

PPI treatment, 61% of the children developed minor degrees of ECL cell hyperplasia

with no known clinical significance and with no development of atrophic gastritis or

carcinoid tumours.

5.2

Pharmacokinetic properties

Absorption

Esomeprazole is acid labile and is administered orally as gastro-resistant

granules. In vivo conversion to the R-isomer is negligible. Absorption of

esomeprazole is rapid, with peak plasma levels occurring approximately

1-2 hours after 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% plasma protein bound.

Biotransformation

Esomeprazole is completely metabolised by the cytochrome P450 system (CYP). 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.

Elimination

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. Esomeprazole is completely eliminated from plasma

between doses with no tendency for accumulation during once-daily administration.

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.

Linearity/non-linearity

The pharmacokinetics of esomeprazole has been studied in doses up to 40 mg b.i.d.

The area under the plasma concentration-time curve increases with repeated

administration of esomeprazole. This increase is dose-dependent and results in a

more than dose proportional increase in AUC 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.

Special patient populations

Poor metabolisers

Approximately 2.9±1.5% of the population lack a functional CYP2C19 enzyme and

are called poor metabolisers. In these individuals the metabolism of esomeprazole is

probably mainly 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 peak plasma concentrations were

increased by about 60%. These findings have no implications for the posology 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 posology of

esomeprazole.

Hepatic impairment

The metabolism of esomeprazole in patients with mild to moderate liver dysfunction

may be impaired. The metabolic rate is decreased in patients with severe liver

dysfunction resulting in a doubling of the area under the plasma concentration-time

curve of 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.

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.

Older people

The metabolism of esomeprazole is not significantly changed in elderly

subjects (71-80 years of age).

Paediatric population

Adolescents 12-18 years:

Following repeated dose administration of 20 mg and 40 mg esomeprazole, the total

exposure (AUC) and the time to reach maximum plasma drug concentration (t

) in

12 to 18 year-olds was similar to that in adults for both esomeprazole doses.

5.3

Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies

of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential,

toxicity to reproduction and development. Adverse reactions not observed in clinical

studies, but seen in animals at exposure levels similar to clinical exposure levels and

with possible relevance to clinical use were as follows:Carcinogenicity studies in the

rat with the racemic mixture have shown gastric ECL-cell hyperplasia and

carcinoids. These gastric effects in the rat are the result of sustained, pronounced

hypergastrinaemia secondary to reduced production of gastric acid and are observed

after long-term treatment in the rat with inhibitors of gastric acid secretion.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Pellets:

Methacrylic acid-ethyl acrylate copolymer (1:1)

Talc

Triethyl citrate

Hypromellose 3cPs

Sugar spheres

Magnesium stearate

Hydroxypropyl cellulose

Glycerol Monostearate 40-55

Polysorbate 80

Tablet core:

Microcrystalline cellulose

Povidone K29/32

Macrogol 6000

Crospovidone Type A

Sodium stearyl fumarate

Tablet coating:

Hypromellose

Titanium dioxide (E171)

Macrogol/PEG 400

Red iron oxide (E172)

Yellow iron oxide (E172)

6.2

Incompatibilities

Not applicable

6.3

Shelf life

2 years

[Bottles only]: After first opening of the bottle: 6 months.

6.4

Special precautions for storage

Do not store above 30°C.

6.5

Nature and contents of container

HDPE bottles containing a desiccant and closed with a LDPE cap.

Pack sizes: 30, 100, 250 or 500 tablets

Aluminium-PVC/PVDC or OPA/Aluminium/PVC-Aluminium foil blisters

Pack sizes: 7, 14, 28, 30, 50, 56, 60, 90, 98, 100 or 140 tablets

Not all pack sizes may be marketed.

6.6

Special precautions for disposal

Administration through gastric tube

Put the tablet into an appropriate syringe and fill the syringe with

approximately 25 ml water and approximately 5 ml air. For some tubes,

dispersion in 50 ml water is needed to prevent the pellets from clogging the

tube.

Immediately shake the syringe until tablet has disintegrated.

Hold the syringe with the tip up and check that the tip has not clogged.

Attach the syringe to the tube whilst maintaining the above position.

Shake the syringe and position it with the tip pointing down. Immediately

inject 5-10 ml into the tube. Invert the syringe after injection and shake (the

syringe must be held with the tip pointing up to avoid clogging of the tip).

Turn the syringe with the tip down and immediately inject another 5-10 ml

into the tube. Repeat this procedure until the syringe is empty.

Fill the syringe with 25 ml of water and 5 ml of air and repeat step 5 if

necessary to wash down any sediment left in the syringe. For some tubes,

50 ml water is needed.

Special precautions for disposal

No special requirements

7

MARKETING AUTHORISATION HOLDER

Accord-UK Ltd

(Trading style: Accord)

Whiddon Valley

Barnstaple

Devon

EX32 8NS

8

MARKETING AUTHORISATION NUMBER(S)

PL 00142/1168

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

28/01/2013

10

DATE OF REVISION OF THE TEXT

28/11/2019

Esomeprazole 20 mg gastro-resistant tablets

Boots Heartburn and Acid Reflux Control 20 mg gastro-resistant tablets

PL 36390/0189

1

Public Assessment Report

UKPAR

Esomeprazole 20 mg gastro-resistant tablets

&

Boots Heartburn and Acid Reflux Control 20mg gastro-resistant

tablets

(esomeprazole magnesium dihydrate)

UK Licence Number: PL 36390/0189

CIPLA (EU) LIMITED

Esomeprazole 20 mg gastro-resistant tablets

Boots Heartburn and Acid Reflux Control 20 mg gastro-resistant tablets

PL 36390/0189

2

LAY SUMMARY

Esomeprazole 20 mg gastro-resistant tablets

&

Boots Heartburn and Acid Reflux Control 20mg gastro-resistant tablets

(Esomeprazole, gastro-resistant tablets, 20 mg)

This is a summary of the Public Assessment Report (PAR) for Esomeprazole 20 mg gastro-resistant

tablets, also named Boots Heartburn and Acid Reflux Control 20mg gastro-resistant tablets (PL

36390/0189). It explains how Esomeprazole 20 mg gastro-resistant tablets / Boots Heartburn and Acid

Reflux Control 20mg gastro-resistant tablets were assessed and their authorisation recommended, as

well as their conditions of use. It is not intended to provide practical advice on how to use Esomeprazole

20 mg gastro-resistant tablets / Boots Heartburn and Acid Reflux Control 20mg gastro-resistant tablets.

The product will be referred to as Esomeprazole Tablets throughout the remainder of this public

assessment report (PAR).

For practical information about using Esomeprazole Tablets, patients should read the package leaflet or

contact their doctor or pharmacist.

What are Esomeprazole Tablets

and what are they used for?

Esomeprazole Tablets are a ‘hybrid generic medicine’. This means that they are similar to a reference

medicine containing the same active substance but is available for treatment of a different condition.

The reference medicine for this product is Nexium 20mg Tablets, PL 17901/0068 (AstraZeneca).

Esomeprazole Tablets are used in the short-term treatment of reflux symptoms (e.g. heartburn and acid

regurgitation) in adults.

How do Esomeprazole Tablets work?

The active ingredient in this medicine is called esomeprazole magnesium trihydrate and is one of a

group of medicines called ‘proton pump inhibitors’. They work by reducing the amount of acid that your

stomach produces.

How are Esomeprazole Tablets used?

The pharmaceutical form of this medicine is a gastro-resistant tablet. The route of administration of this

medicine is oral (by mouth).

Dose

The recommended dose of one tablet (20 mg) should not be exceeded, even if the patient does not feel

an improvement immediately. Tablets may need to be taken for 2 or 3 days in a row before reflux

symptoms (for example, heartburn and acid regurgitation) get better. The treatment length is up to 14

days.

When reflux symptoms have completely gone the patient should stop taking this medicine. If reflux

symptoms get worse or do not improve after taking this medicine for 14 days in a row, the patient should

consult a doctor. If the patient has persistent or longstanding, frequently recurring symptoms even after

treatment with this medicine, he/she should contact his/her doctor.

Esomeprazole 20 mg gastro-resistant tablets

Boots Heartburn and Acid Reflux Control 20 mg gastro-resistant tablets

PL 36390/0189

3

Taking this medicine

The tablet can be taken at any time of the day either with food or on an empty stomach. The tablet

should be swallowed whole with a glass of water, without chewing or crushing the tablet. This is

because the tablet contains coated pellets, which stop the medicine from being broken down by the acid

in your stomach. It is important not to damage the pellets.

Please read section 3 of the package leaflet for detailed information on dosing recommendations, the

route of administration (including an alternative method of taking this medicine), and the duration of

treatment.

This medicine can be obtained without a prescription.

What benefits of Esomeprazole Tablets have been shown in studies?

Studies in patients have been limited to tests to determine that the medicine is bioequivalent to the

reference medicine, Nexium 20 mg Tablets (AstraZeneca Limited). Two medicines are bioequivalent

when they produce the same measure of therapeutic effect in the body.

What are the possible side effects of this medicine?

Like all medicines, this medicine can cause side effects, although not everybody gets them.

For the full list of all side effects reported with this medicine, see section 4 of the package leaflet

available on the MHRA website.

For the full list of restrictions, see the package leaflet.

Why was this medicine approved?

The MHRA decided that this medicine’s benefits are greater than its risks and recommended that it be

approved for use.

What measures are being taken to ensure the safe and effective use of Esomeprazole Tablets?

A risk management plan (RMP) has been developed to ensure that Esomeprazole Tablets are used as

safely as possible. Based on this plan, safety information has been included in the Summary of Product

Characteristics and the package leaflet for Esomeprazole Tablets including the appropriate precautions

to be followed by healthcare professionals and patients.

Known side effects are continuously monitored. Furthermore new safety signals reported by

patients/healthcare professionals will be monitored/reviewed continuously.

Other information about this medicine

The MHRA agreed to grant a marketing Authorisation for Esomeprazole Tablets on 28 November 2016.

The full PAR for this medicine follows this summary.

This summary was last updated in January 2017.

Esomeprazole 20 mg gastro-resistant tablets

Boots Heartburn and Acid Reflux Control 20 mg gastro-resistant tablets

PL 36390/0189

4

TABLE OF CONTENTS

Introduction

Page 5

Quality aspects

Page 6

Non-clinical aspects

Page 7

Clinical aspects

Page 8

User consultation

Page 12

Overall conclusion, benefit/risk assessment and

recommendation

Page 12

Esomeprazole 20 mg gastro-resistant tablets

Boots Heartburn and Acid Reflux Control 20 mg gastro-resistant tablets

PL 36390/0189

5

I

INTRODUCTION

Based on the review of the data on quality, safety and efficacy, the Medicines and Healthcare products

Regulatory Agency (MHRA) granted Cipla EU Limited, a Marketing Authorisation for the medicinal

product Esomeprazole 20 mg gastro-resistant tablets / Boots Heartburn and Acid Reflux Control 20mg

gastro-resistant tablets (PL 36390/0189). The product is a general sales list (GSL) medicine indicated for

the short-term treatment of reflux symptoms (e.g. heartburn and acid regurgitation) in adults.

This application was submitted under Article 10(3) of Directive 2001/83/EC, as amended, as a hybrid

application, cross-referring to Nexium 20 mg Tablets which were originally licenced on 27 July 2000 to

AstraZeneca UK Limited (PL 17901/0068).

Esomeprazole magnesium dihydrate is the S-isomer of omeprazole and reduces gastic acid secretion

through a specific targeted mechanism of action. It is a specific inhibitor of the acid pump in the parietal

cell. Both the R- and S-isomer of omeprazole have similar pharmacodynamics activity.

Two bioequivalence studies were submitted to support this application:

A study under fed conditions comparing the applicant’s test product Esomeprazole 20 mg

gastro-resistant tablets (each tablet containing esomeprazole magnesium dihydrate equivalent to

20 mg esomeprazole) with the reference product Nexium 20 mg tablets (each gastro-resistant

tablet contains esomeprazole magnesium trihydrate equivalent to 20 mg esomeprazole)

authorised to AstraZeneca Ltd, UK.

A study under fasting conditions comparing the applicant’s test product Esomeprazole 20 mg

gastro-resistant tablets (each tablet containing esomeprazole magnesium dihydrate equivalent to

20 mg esomeprazole), with the reference product

Nexium

20 mg Tablets

(each gastro-resistant

tablet contains esomeprazole magnesium trihydrate equivalent to 20 mg esomeprazole)

authorised to AstraZeneca Ltd, UK..

With the exception of the results of the bioequivalence studies detailed above, no new clinical data were

submitted, which is acceptable given that this application was based on the product being shown to be

bioequivalent to an originator product that has been in clinical use for over 10 years.

No new or unexpected safety concerns arose during the review of information provided by the

Marketing Authorisation Holder and it was, therefore, judged that the benefits of taking Esomeprazole

Tablets outweigh the risks and a Marketing Authorisation was granted.

Esomeprazole 20 mg gastro-resistant tablets

Boots Heartburn and Acid Reflux Control 20 mg gastro-resistant tablets

PL 36390/0189

6

II

QUALITY ASPECTS

II.1

Introduction

Each tablet contains 21.75 mg esomeprazole magnesium dihydrate (equivalent to 20 mg esomeprazole).

Other ingredients consist of the pharmaceutical excipients: hypromellose, sucrose,

maize starch, liquid glucose, talc, methacrylic acid – ethylacrylate copolymer (1:1) dispersion 30 %,

sodium lauryl sulfate, polysorbate 80, triethyl citrate, macrogol, microcrystalline cellulose,

crospovidone, stearyl alcohol, silica colloidal anhydrous, lactose monohydrate and cellulose

microcrystalline, magnesium stearate, titanium dioxide (E171), iron oxide red (E172).

The product is packed into oriented polyamide (OPA), aluminium, polyvinyl chloride (PVC)/aluminium

blisters and is available in pack sizes of 7 and 14 tablets. Not all pack sizes may be marketed.

Satisfactory specifications and Certificates of Analysis have been provided for all packaging

components.

II.2.

Drug Substance

INN:

Esomeprazole magnesium dihydrate

Chemical name:

Esomeprazole magnesium dihydrate is magnesium bis[5-methoxy-2-[(S)-[(4-

methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl]-1H-benzimidazol-1-ide]

dihydrate.

Structural formula:

Molecular formula:

Molecular weight:

749.2

Appearance:

White or slightly coloured powder, slightly hygroscopic.

Solubility:

It is slightly soluble in water, soluble in methanol, practically insoluble in heptane.

Esomeprazole magnesium dihydrate is the subject of a European Pharmacopoeia monograph and the

active supplier manufacturer applies requirements of the Ph.Eur. monograph.

Appropriate proof-of-structure data have been supplied for the active substance. All potential known

impurities have been identified and characterised.

An appropriate specification is provided for the active substance. Analytical methods have been

appropriately validated and are satisfactory for ensuring compliance with the relevant specification.

Batch analyses data are provided that comply with the proposed specification.

Satisfactory Certificates of Analysis have been provided for all working standards used.

Esomeprazole 20 mg gastro-resistant tablets

Boots Heartburn and Acid Reflux Control 20 mg gastro-resistant tablets

PL 36390/0189

7

II.3.

Medicinal Product

Pharmaceutical Development

The objective of the development programme was to formulate safe, efficacious, stable tablets

containing 21.75 mg esomeprazole magnesium dihydrate per tablet that were comparable in

performance to the reference product Nexium® 20 mg Tablets (AstraZeneca Limited). A satisfactory

account of the pharmaceutical development has been provided.

Comparable

in vitro

dissolution profiles have been provided for this product and the reference product

Nexium® 20 mg Tablets (AstraZeneca Limited).

All excipients comply with their respective European Pharmacopoeia monographs. Satisfactory

Certificates of Analysis have been provided for all excipients. Suitable batch analysis data have been

provided for each excipient.

It has been stated that the excipients are not of human or animal origin, except for the lactose. A signed

TSE / BSE risk free declaration has been provided by the manufacturer of lactose monohydrate and is

acceptable.

No genetically modified organisms (GMO) have been used in the preparation of this product.

Manufacture of the product

A satisfactory batch formula has been provided for the manufacture of the product, along with an

appropriate account of the manufacturing process. The manufacturing process has been validated at

commercial-scale batch size and shown satisfactory results.

Finished Product Specification

The finished product specification proposed is acceptable. Test methods have been described that have

been adequately validated. Batch data have been provided that comply with the release specification. In-

house working standards are used which are compared to PhEur reference materials where available.

Representative certificates have been provided.

Stability of the Product

Finished product stability studies were performed in accordance with current guidelines on batches of

finished product in the packaging proposed for marketing. The data from these studies support a

shelf-life of 2 years with no special storage conditions.

Suitable post approval stability commitments have been provided to place a batch of the finished product

under stability testing conditions each year.

II.4

Discussion on chemical, pharmaceutical and biological aspects

There are no objections to the approval of this application from a pharmaceutical viewpoint.

III

NON-CLINICAL ASPECTS

III.1

Introduction

As the pharmacodynamic, pharmacokinetic and toxicological properties of esomeprazole magnesium

dihydrate are well-known, no new non-clinical studies are required and none have been provided.

Esomeprazole 20 mg gastro-resistant tablets

Boots Heartburn and Acid Reflux Control 20 mg gastro-resistant tablets

PL 36390/0189

8

The Non-clinical Overview is acceptable in terms of the literature review, given the extensive clinical

experience with esomeprazole. There were no new findings identified that would change the risk:

benefit balance for esomeprazole.

The grant of a Marketing Authorisation is recommended.

III.2

Pharmacology

Not applicable for this product type. Refer to section ‘III.1; Introduction’ detailed above.

III.3

Pharmacokinetics

Not applicable for this product type. Refer to section ‘III.1; Introduction’ detailed above.

III.4

Toxicology

Not applicable for this product type. Refer to section ‘III.1; Introduction’ detailed above.

III.5

Ecotoxicity/environmental risk assessment (ERA)

Since Esomeprazole Tablets are intended for generic substitution, this medicinal product will not lead to

an increased exposure to the environment. An environmental risk assessment is therefore not deemed

necessary.

III.6

Discussion on the non-clinical aspects

No new non-clinical studies were conducted or necessary for this type of application.

There are no objections to the approval of this application from a non-clinical viewpoint.

IV

CLINICAL ASPECTS

IV.1

Introduction

The clinical pharmacology of esomeprazole magnesium dihydrate is well-known. With the exception of

data from the bioequivalence study detailed below, no new pharmacodynamics or pharmacokinetic data

are provided or are required for this application.

No new efficacy or safety studies have been performed and none are required for this type of

application. A comprehensive review of the published literature has been provided by the applicant,

citing the well-established clinical pharmacology, efficacy and safety of esomeprazole magnesium

dihydrate.

Based on the data provided, Esomeprazole Tablets can be considered bioequivalent to Nexium 20 mg

Tablets (AstraZeneca Limited).

IV.2

Pharmacokinetics

support

this

application,

applicant

submitted

following

reports

single

dose

bioequivalence studies, one conducted under fasting conditions and one conducted under fed conditions.

FASTING STUDY

A randomised, balanced, open label, two-sequence, two-treatment, two-period, crossover, single dose,

bioequivalence

study

Esomeprazole

gastro-resistant

tablets

(each

tablet

containing

esomeprazole magnesium dihydrate equivalent to 20 mg esomeprazole) with Nexium® 20 mg Tablets

Esomeprazole 20 mg gastro-resistant tablets

Boots Heartburn and Acid Reflux Control 20 mg gastro-resistant tablets

PL 36390/0189

9

(each

gastro-resistant

tablet

contains

esomeprazole

magnesium

trihydrate

equivalent

esomeprazole) authorised to AstraZeneca Ltd, UK, in 30 normal, healthy, adult, male and female human

subjects (25 males and 5 females) under fasting conditions

After an overnight fast subjects were administered a single oral dose of the test or the reference product

with 240 mL of water. The duration of study was 9 days including the washout period of 7 days.

A total of 21 blood samples (5 mL each) were collected from the subjects in each period of the study

from pre dose to 16.00 hours post-dose. Analysis of plasma concentrations of esomeprazole was

performed by a validated LC-MS/MS analytical method. A non-compartmental method was used to

calculate the pharmacokinetic parameters using drug concentration time profile. Statistical comparison

of the pharmacokinetic parameters of both the formulations was performed to assess the bioequivalence

of esomeprazole. Bioequivalence was to be concluded if the 90% confidence intervals of the mean ratios

(based on log-transformed data) were within the range 80.00-125.00% for C

and AUC

with respect

to esomeprazole.

Summary statistics for pharmacokinetic parameters for esomeprazole magnesium dihydrate are shown

below:

Treatment

AUC

τ

ng/ml/h

AUC

ng/ml/h

C

max

ng/ml

t

max

h

T

1/2

h

Test

2533.05

2572.52

944.75

2.26

1.37

Reference

2599.77

2642.85

984.13

2.24

1.41

*Ratio

(90%

CI)

94.85

(88.52-101.64)

95.43

(87.65-103.90)

AUC

area under the plasma concentration-time curve from time zero to infinity

AUC

τ

area under the plasma concentration-time curve from time zero to t hours

C

max

maximum plasma concentration

T

max

time for maximum concentration (median)

T

1/2

half-life

*ln-transformed values

Esomeprazole 20 mg gastro-resistant tablets

Boots Heartburn and Acid Reflux Control 20 mg gastro-resistant tablets

PL 36390/0189

10

FED STUDY

A randomised, balanced, open label, two-treatment, four-period, two-sequence, single dose, replicate

crossover bioequivalence study was performed to demonstrate the bioequivalence of Esomeprazole 20

mg gastro-resistant tablets (each tablet containing esomeprazole magnesium dihydrate equivalent to 20

mg esomeprazole) with Nexium® 20mg tablets (each gastro-resistant tablet contains esomeprazole

magnesium trihydrate equivalent to 20 mg esomeprazole) authorised to AstraZeneca Ltd, UK in a total

of 40 healthy adult male human subjects under fed conditions.

After an overnight fasting period subjects were given a high fat high calorie breakfast prior to dosing. A

single dose of one tablet of either the test or reference product was administered orally with 240 ml of

drinking water at the time of dosing. A washout period of 7 days was given between the doses.

A total of 20 blood samples of 5 ml each were collected during each study period from pre-dose

(collected within 90 minutes prior to dosing) to 24.00 hours (post-dose) in the labelled vacuum blood

collection tube containing K

EDTA as an anticolagulant.

Analysis of plasma samples for concentrations of esomeprazole was completed using a validated LC-

MS/MS method. A non-compartmental method was used to calculate pharmacokinetic parameters using

drug concentrations versus time profile. Statistical comparison of the pharmacokinetic parameters of

both the test and reference products were performed and assessed for bioequivalence. Bioequivalence

was to be concluded if the 90% confidence intervals of the mean ratios (based on log-transformed data)

were within the range 80.00-125.00% for C

and AUC

with respect to esomeprazole.

Summary statistics for pharmacokinetic parameters for esomeprazole magnesium dihydrate are shown

below:

*ln-transformed values

Conclusion

The 90% confidence intervals for AUC

and C

were within the acceptance range for all studies.

Bioequivalence has been demonstrated between the test and reference products.

IV.3

Pharmacodynamics

No new pharmacodynamic data were submitted and none were required for an application of this type.

IV.4

Clinical efficacy

No new efficacy data were submitted and none were required for an application of this type.

Treatment

AUC

τ

ng/ml/h

AUC

ng/ml/h

C

max

ng/ml

t

max

h

T

1/2

h

Test

2086.80

2135.74

533.55

3.67

1.49

Reference

2052.16

2091.62

577.27

3.67

1.45

*Ratio (90%

CI)

100.14

(92.50-108.40)

94.93

(86.36-104.36)

AUC

area under the plasma concentration-time curve from time zero to infinity

AUC

τ

area under the plasma concentration-time curve from time zero to t hours

C

max

maximum plasma concentration

T

max

time for maximum concentration (median)

T

1/2

half-life

Esomeprazole 20 mg gastro-resistant tablets

Boots Heartburn and Acid Reflux Control 20 mg gastro-resistant tablets

PL 36390/0189

11

IV.5

Clinical safety

No new safety data were submitted and none were required for this application.

IV.6

Risk Management Plan (RMP)

The Marketing Authorisation Holder (MAH) has submitted a risk management plan (RMP), in

accordance with the requirements of Directive 2001/83/EC as amended, describing the

pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise

risks relating to esomeprazole magnesium dihydrate.

A summary of safety concerns and planned risk minimisation activities, as approved in the RMP, is

provided below:

Routine pharmacovigilance and routine risk minimisation are proposed for all safety concerns.

Esomeprazole 20 mg gastro-resistant tablets

Boots Heartburn and Acid Reflux Control 20 mg gastro-resistant tablets

PL 36390/0189

12

IV.7

Discussion on the clinical aspects

There are no objections to the approval of this application from a clinical viewpoint

.

The grant of a Marketing Authorisation is recommended for this application.

V

User consultation

User testing of the package leaflet has been accepted, based on a bridging report provided by the

applicant making reference to Esomeprazole 20 & 40 mg Gastro-Resistant Tablets (PL 36390/0159-

0160). The bridging report has successfully demonstrated how the key messages in the daughter PIL are

covered within the parent PIL and has justified any differences. The design and layout are sufficiently

identical to permit a comparison.

VI

Overall conclusion, benefit/risk assessment and recommendation

The quality of the product is acceptable, and no new non-clinical or clinical safety concerns have been

identified. Extensive clinical experience with esomeprazole magnesium dihydrate is considered to have

demonstrated the therapeutic value of the compound. The benefit-risk is, therefore, considered to be

positive.

Esomeprazole 20 mg gastro-resistant tablets

Boots Heartburn and Acid Reflux Control 20 mg gastro-resistant tablets

PL 36390/0189

13

Summary of Product Characteristics (SmPC), Patient Information Leaflet (PIL) and Labels

In accordance with Directive 2010/84/EU the Summaries of Product Characteristics (SmPC) and Patient

Information Leaflets (PIL) for products granted Marketing Authorisations at a national level are

available on the MHRA website.

The approved labelling for Esomeprazole Tablets is presented below:

Esomeprazole 20 mg gastro-resistant tablets

Boots Heartburn and Acid Reflux Control 20 mg gastro-resistant tablets

PL 36390/0189

14

Similar products

Search alerts related to this product

View documents history

Share this information