NEXIUM TABLETS 40 MG

Israel - English - Ministry of Health

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Active ingredient:
ESOMEPRAZOLE
Available from:
ASTRA ZENECA (ISRAEL) LTD
ATC code:
A02BC05
Pharmaceutical form:
TABLETS
Composition:
ESOMEPRAZOLE 40 MG
Administration route:
PER OS
Prescription type:
Required
Manufactured by:
ASTRA ZENECA AB., SWEDEN
Therapeutic group:
ESOMEPRAZOLE
Therapeutic area:
ESOMEPRAZOLE
Therapeutic indications:
Nexium tablets are indicated in adults for:Gastroesophageal Reflux Disease (GERD)- treatment of erosive reflux esophagitis- long-term management of patients with healed esophagitis to prevent relapse- symptomatic treatment of gastroesophageal reflux disease (GERD)In combination with an appropriate antibacterial therapeutic regimen 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 NSAID therapy- healing of gastric ulcers associated with NSAID therapy. - prevention of gastric and duodenal ulcers associated with NSAID therapy in patients at risk.Prolonged treatment after i.v. induced prevention of rebleeding of peptic ulcers.Nexium 40 mg tablets are indicated in adolescents from the age of 12 years for;Gastroesophageal Reflux Disease (GERD)- treatment of erosive reflux esophagitis
Authorization number:
122 53 30238 00
Authorization date:
2011-05-31

Documents in other languages

Patient Information leaflet Patient Information leaflet - Arabic

21-01-2021

Patient Information leaflet Patient Information leaflet - Hebrew

05-09-2017

PATIENT PACKAGE INSERT IN ACCORDANCE WITH

THE PHARMACISTS’ REGULATIONS (PREPARATIONS) - 1986

This medicine is dispensed with a doctor’s prescription only

NEXIUM

20 mg

NEXIUM

40 mg

Tablets

Tablets

Composition

Each tablet contains:

Each tablet contains:

Esomeprazole 20 mg

Esomeprazole 40 mg

(as magnesium trihydrate)

(as magnesium trihydrate)

Read this leaflet carefully in its entirety before using the medicine.

Keep this leaflet; you may need to read it again.

This leaflet contains concise information about the medicine. If you have further questions, refer to the doctor or

pharmacist.

This medicine has been prescribed to treat your ailment. Do not pass it on to others. It may harm them even if it seems

to you that their ailment is similar.

WHAT IS THE MEDICINE INTENDED FOR?

In adults, Nexium 20 mg and Nexium 40 mg are intended for:

For treatment of heartburn, with or without inflammation of the gullet, caused by reflux of gastric acid. Nexium reduces

the production of acid and helps heal the gullet by reducing pain and inflammation.

Treatment of ulcers in the upper part of the gut or stomach caused by

Helicobacter pylori

bacteria. Nexium in

combination with suitable antibiotics, treats the infection and leads to healing of the ulcer and prevention of

recurrence.

Healing of gastric ulcer caused by use of non-steroidal anti-inflammatory drugs (NSAIDs), such as preparations to

treat arthritis (rheumatism).

Prevention of formation of gastric ulcers, if you might possibly develop them as a result of taking non-steroidal anti-

inflammatory drugs (NSAIDs), such as preparations to treat arthritis (rheumatism).

Prolonged treatment with Nexium tablets to prevent recurrent bleeding of a gastric or duodenal ulcer, after primary

intravenous Nexium treatment.

In adolescents, Nexium 20 mg is intended for:

For treatment of heartburn, with or without inflammation of the gullet, caused by reflux of gastric acid. Nexium

reduces the production of acid and helps heal the gullet by reducing pain and inflammation.

Treatment of ulcers in the upper part of the gut or stomach caused by

Helicobacter pylori

bacteria. Nexium in

combination with suitable antibiotics, treats the infection and leads to healing of the ulcer and prevention of

recurrence.

In adolescents, Nexium 40 mg is intended for:

For treatment of heartburn with inflammation of the gullet, caused by reflux of gastric acid. Nexium reduces

the production of acid and helps heal the gullet by reducing pain and inflammation.

Therapeutic group

Proton pump inhibitor (the gastric acid pump).

BEFORE USING THE MEDICINE

Do not use the medicine if:

You have a known sensitivity to any of its ingredients (listed in section 6 Further Information).

You have a known sensitivity to another preparation of the proton pump inhibitors group (preparations to treat

ulcer-like symptoms, e.g.: pantoprazole, lansoprazole, rabeprazole, omeprazole).

You are being treated with nelfinavir (a medicine to treat immune deficiency syndrome [HIV]).

Special warnings regarding use of Nexium

Before treatment with Nexium, tell the doctor if:

You are suffering, or have suffered in the past, from severe liver dysfunction.

You are suffering, or have suffered in the past, from severe kidney dysfunction.

You have suffered in the past from a skin reaction after treatment with a medicine similar to Nexium, which lowers

gastric acidity.

If you are due to have a specific blood test (Chromogranin A).

Nexium may mask the symptoms of other diseases. Therefore, if any of the following occur to you before starting

treatment with Nexium or during treatment with Nexium, refer to the doctor immediately:

You are suffering from unexplained weight loss or you have difficulty swallowing

You are suffering from abdominal pain or from indigestion

You are vomiting food or blood

You have black stools (bloody stools)

If you are taking the medicine as needed (according to the doctor's instructions), please inform the attending doctor,

you must also tell the attending doctor if there is any change in your symptoms.

There is an increased risk of fractures of the hip, wrist and back upon prolonged use for one year or more. Please

inform the doctor if you have been diagnosed with osteoporosis (bone depletion – those having disease are more

prone to fractures) or if you are taking corticosteroids.

If you have a skin rash, especially in areas exposed to the sun, please tell the doctor as soon as possible since

you may need to stop treatment with Nexium. If you experience additional disease symptoms, such as joint pains,

please report to the doctor as well.

If you are taking other medicines

Please tell the attending doctor if you are taking other medicines or if you have just finished treatment with another

medicine, including non-prescription medicines and herbal medicines. This is because Nexium may affect the way

certain medicines work, and certain medicines may affect the way Nexium works.

Do not take Nexium if you are being treated with a preparation that contains nelfinavir (a medicine to treat immune

deficiency syndrome [HIV])

Tell the doctor or the pharmacist if you are taking:

Atazanavir (to treat immune deficiency syndrome – HIV),

Medicines to treat fungal infection (ketoconazole or itraconazole and voriconazole),

Antidepressants (citalopram, imipramine or clomipramine),

Erlotinib (a medicine to treat cancer),

Sedatives (diazepam),

Medicines for epilepsy (phenytoin). If you are taking phenytoin, your doctor will have to monitor your treatment at

the beginning and end of Nexium treatment,

Blood thinners (warfarin), your doctor will have to monitor your treatment at the beginning and end of Nexium

treatment,

Clopidogrel (a medicine used to prevent blood clots),

Medicines for heart problems (digoxin),

If you are taking medicinal treatment for tuberculosis (rifampicin),

A preparation for treatment of depression: St. John’s Wort (

Hypericum perforatum

Medicines intended to treat arterial diseases in the legs that cause intermittent claudication (cilostazol),

Methotrexate (a medicine used at high dosages to treat cancer); if you are taking a high dosage of methotrexate,

your doctor may instruct you to temporarily stop treatment with Nexium,

A medicine to prevent transplant rejection after an organ transplantation (tacrolimus),

Certain medicines to treat malignant tumors (e.g.: erlotinib),

Medicines to accelerate gastric emptying (cisapride) in combined treatment with Nexium,

If you are receiving Nexium together with clarithromycin and amoxicillin to treat an ulcer caused by

Helicobacter pylori

bacteria, it is important that you tell the doctor of any other medicine you are taking.

Use of Nexium and food

The tablet can be taken with food or on an empty stomach.

Pregnancy and breastfeeding

If you are pregnant, think you are pregnant or are planning to become pregnant, consult the doctor before taking this

medicine.

It is not known whether Nexium passes into breast milk. Therefore, do not use Nexium if you are breastfeeding.

Driving and use of machinery

Nexium shouldn’t affect your ability to drive or use machinery. However, side effects such as dizziness or blurred

vision may occur. If you suffer from these side effects, do not drive and do not use machinery.

Important information regarding some of the ingredients of the medicine

The tablets contain sucrose (certain type of sugar). If you have been told by the doctor that you cannot digest certain

sugars, consult the doctor before taking this medicine.

Nexium 20 mg tablets – each tablet contains 28 mg sucrose

Nexium 40 mg tablets – each tablet contains 30 mg sucrose

HOW SHOULD YOU USE THE MEDICINE?

Always use according to the doctor’s instructions. Check with the doctor or pharmacist if you are uncertain.

The doctor will tell you about taking the medicine (how many tablets and when to take). The strength of the tablet and

duration of treatment are determined by the doctor in accordance with the disease from which you are suffering.

If you are taking this medicine for a long time (particulary if you are taking it for more than a year) the doctor may want

to perform certain tests.

If your doctor has told you to take this medicine as needed, tell your doctor if your symptoms change.

Instructions for use

The tablet can be taken at any time during the day.

The tablet can be taken with food or on an empty stomach.

Swallow the medicine whole, with half a glass of water, do not chew or crush the parts of the tablet. The tablet

contains coated pellets to prevent breakdown of the medicine by the gastric acid and it is therefore important not to

crush the particles.

Patients with difficulties swallowing the tablet can crumble the tablet in half a glass of water (do not use fizzy water

or any other liquid). Stir until the tablet disintegrates (an unclear solution will be obtained). Mix well before drinking;

can be drunk immediately or within 30 minutes at the most. Rinse the glass with water and drink to ensure the

remainder of the medicine is taken. The solid pieces contain the medicine – do not chew or crush them.

Elderly

Dose adjustment is not required in the elderly.

If you accidentally took a higher dosage or if a child has accidentally swallowed the medicine, immediately refer to the

doctor or proceed to a hospital emergency room, and bring the package of the medicine with you.

If you forgot to take this medicine at the designated time, take a dose as soon as you remember. However, if you

remembered close to the time for the next dose, do not take the forgotten dose; take the next dose at the designated

time.

How can you contribute to the success of the treatment?

Complete the treatment regimen recommended by the doctor.

Even if there is an improvement in your health, do not stop treatment with the medicine without consulting the doctor.

Care should be taken to implement the dosing instructions accurately and ask the doctor in case of any doubt.

4. SIDE EFFECTS

As with any medicine, use of Nexium may cause side effects in some users. Do not be alarmed when reading the list of

side effects. You may not suffer from any of them.

Side effects requiring special attention:

Stop treatment and refer to the doctor immediately in the following cases:

sudden wheezing, shortness of breath, swelling of the lips, tongue and throat or body, rash, fainting or difficulties in

swallowing – these are signs of a severe allergic reaction.

reddening of the skin with blisters or peeling. There may also be blisters and bleeding in the lips, eyes, mouth,

nose and genitals. This could be Stevens-Johnson syndrome or toxic epidermal necrolysis.

yellowing of the skin or whites of the eyes, dark urine and tiredness can be symptoms of liver problems.

These effects are rare and affect less than 1 in 1,000 people.

Common side effects, occur frequently (affect up to one patient in 10):

headache

diarrhea, stomach pain, constipation, flatulence

nausea and vomiting

Uncommon side effects (affect up to one patient in 100):

swelling of the legs and ankles

sleeping problems (insomnia)

dizziness, tingling feelings (“pins and needles”)

sleepiness

spinning feeling (vertigo)

dry mouth

changes in liver function blood tests

skin rash, blistering and itching

fractures of the hip, wrist or spine (when using Nexium at a high dosage for a long time)

increased liver enzymes

Rare side effects (affect up to one patient in 1,000):

blood problems such as a reduced number of white cells or platelets - can cause weakness, bruising or increased

risk of infections

low levels of sodium in the blood - may cause weakness, vomiting and cramps

agitation, confusion, depression

taste changes

eye problems such as blurred vision

sudden shortness of breath (bronchospasm)

mouth infection

a fungal infection that may affect the gut

liver problems, including jaundice, that may cause yellowing of the skin, dark urine and tiredness

hair loss

skin rash on exposure to sun

joint pains

muscle pains

feeling ill and lacking energy

increased sweating

Very rare side effects (affect up to one in 10,000 patients):

sudden onset of a severe rash, skin blistering or peeling. This may be accompanied by high fever and joint pains

(erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis)

changes in blood count, agranulocytosis (reduction in white blood cells)

aggression

hallucinations

severe liver problems leading to liver failure and inflammation of the brain

muscle weakness

severe kidney problems

enlarged breasts in men

Side effects of unknown frequency (frequency of the effects cannot be estimated from the available data):

low magnesium levels in the body: this problem may be serious. Low magnesium levels in the body can occur to

certain people who took medical preparations from the proton pump inhibitors group (gastric acid pump) such as

Nexium, for at least three months. If the magnesium levels drop, there may be signs of low magnesium levels.

Please inform your doctor immediately if you experience the following signs:

dizziness

disorientation

fatigue

convulsions

increased heart rate

involuntary muscle contractions

low blood magnesium level, can cause low blood calcium and/or low blood potassium levels

If you are required to take Nexium for a long time, your doctor may check the magnesium levels in your body

before or during treatment with Nexium.

inflammation in the gut (causes diarrhea)

Rash, usually with joint pain

In very rare cases, Nexium may affect the white blood cells and lead to immune deficiency. If you have an infection

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

pain in the head and neck, throat or mouth or difficulties in urinating, consult the doctor immediately to rule out the

possibility of lack of white blood cells (agranulocytosis) by a blood test. You must tell the doctor that you are taking

Nexium.

If a side effect occurs, if any of the side effects worsens or if you suffer from a side effect not mentioned in this leaflet,

consult the doctor.

Side effects can be reported to the Ministry of Health by clicking on the link “Report Side Effects of Drug Treatment”

found on the Ministry of Health homepage (www.health.gov.il) that directs you to the online form for reporting side

effects, or by entering the link:

https://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@moh.gov.il

HOW SHOULD THE MEDICINE BE STORED?

Avoid poisoning! This medicine and any other medicine must be kept in a close place out of the reach of children

and/or infants in order to avoid poisoning.

Do not induce vomiting unless explicitly instructed to do so by the doctor!

Do not take medicines in the dark! Check the label and the dose each time you take medicine. Wear glasses if you

need them.

Keep this medicine in a cool and dry place.

Do not store this medicine at a temperature that exceeds 30°C. Even when stored as per the recommended

packaging/storage conditions, medicines may be kept for a limited period only. Do not use the medicine after the

expiry date (exp. date) appearing on the package. The expiry date refers to the last day of that month. In any case

of doubt, consult the pharmacist who dispensed the medicine to you.

Do not store different medicines in the same package.

FURTHER INFORMATION

In addition to the active ingredient, the medicine also contains:

Microcrystalline cellulose, methacrylic acid ethylacrylate copolymer (1:1), sugar spheres, hypromellose, talc, triethyl

citrate, hyprolose, crospovidone, macrogols, titanium dioxide (E 171), glycerol monostearate 40-55, magnesium

stearate, polysorbate 80, sodium stearyl fumarate, iron oxide (20 mg and 40 mg tablets: reddish-brown; 20 mg tablets:

yellow) (E 172), synthetic paraffin.

What the medicine looks like:

Nexium 20 mg tablets – a rectangular, biconvex, light pink tablet, with 20mg imprinted on one side and

imprinted on

the other side.

Nexium 40 mg tablets – a rectangular, biconvex, pink tablet, with 40mg imprinted on one side and

imprinted on the

other side.

Registration number of the medicine in the National Drug Registry of the Ministry of Health:

20 mg: 122 52 30237 00/11

40 mg: 122 53 30238 00/11

Manufacturer:

AstraZeneca AB,

Sodertalje, Sweden

Registration holder:

AstraZeneca (Israel) Ltd.,

P.O.B. 1455, Hod Hasharon 4524075.

The format of this leaflet was determined by the Ministry of Health and its content was checked and approved by it in

August 2017.

This leaflet format has been determined by the Ministry of Health and the content thereof has been

checked and approved. Date of approval July 2016.

SUMMARY OF PRODUCT CHARACTERISTICS

1.

Name of the Medicinal Product

NEXIUM

20 mg Tablets

NEXIUM

40 mg Tablets

2.

Qualitative and Quantitative Composition

Each tablet contains: 20 mg esomeprazole (as magnesium trihydrate).

Each tablet contains: 40 mg esomeprazole (as magnesium trihydrate).

Excipients: Nexium 20 mg: Sucrose 28 mg. Nexium 40 mg: Sucrose 30 mg.

For a full list of excipients see section 6.1.

3.

Pharmaceutical Form

Gastro-resistant tablet

20 mg: A light pink, oblong, biconvex, film-coated tablet engraved 20 mg on one side and

on the

other side.

40 mg: A pink, oblong, biconvex, film-coated tablet engraved 40 mg on one side and

on the other

side.

4.

Clinical Particulars

4.1

Therapeutic indications

NEXIUM tablets are indicated for:

Gastroesophageal Reflux Disease (GERD)

treatment of erosive reflux esophagitis

long-term management of patients with healed esophagitis to prevent relapse

symptomatic treatment of gastroesophageal reflux disease (GERD)

In combination with an appropriate antibacterial therapeutic regimen 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 NSAID therapy

healing of gastric ulcers associated with NSAID therapy.

prevention of gastric and duodenal ulcers associated with NSAID therapy in

patients at risk.

Prolonged treatment after i.v. induced prevention of rebleeding of peptic ulcers.

4.2

Posology and 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.

patients

cannot

swallow,

tablets

dispersed

non-carbonated

water

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.

Gastroesophageal Reflux Disease (GERD)

- treatment of erosive reflux esophagitis

40 mg once daily for 4 weeks.

An additional 4 weeks treatment is recommended for patients in whom esophagitis has not

healed or who have persistent symptoms.

- long-term management of patients with healed esophagitis to prevent relapse

20 mg once daily.

- symptomatic treatment of gastroesophageal reflux disease (GERD)

20 mg once daily in patients without esophagitis. If symptom control has not been achieved after

four weeks, the patient should be further investigated. Once symptoms have resolved, subsequent

symptom control can be achieved using an on-demand regimen taking 20 mg once daily, when

needed. In NSAID treated patients at risk of developing gastric and duodenal ulcers, subsequent

symptom control using an on demand regimen is not recommended.

Adults

In combination with an appropriate antibacterial therapeutic regimen 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.

20 mg NEXIUM with 1 g amoxicillin and 500 mg clarithromycin, all twice daily for 7 days.

Patients requiring NSAID therapy

- healing of gastric ulcers associated with NSAID therapy: The usual dose is 20 mg once daily. The

treatment duration is 4-8 weeks.

- prevention of gastric and duodenal ulcers associated with NSAID therapy in patients at risk: 20 mg

once daily.

Prolonged

treatment

after

i.v.

induced

prevention

of

rebleeding

of

peptic

ulcers.

40 mg once daily for 4 weeks after i.v. induced prevention of rebleeding of peptic ulcers.

Children and adolescents

Safety and effectiveness in pediatric patients have not been established.

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).

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 NEXIUM should not be exceeded, (see section

5.2).

Elderly

Dose adjustment is not required in the elderly.

4.3

Contraindications

Known hypersensitivity to esomeprazole, substituted benzimidazoles or any other constituents of the

formulation. Esomeprazole should not be administrated with nelfinavir (see section 4.5).

4.4

Special warnings and special 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 NEXIUM 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.

HypomagnesaemiaSevere 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 Nexium. 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 400 mg with 100 mg of ritonavir; esomeprazole 20 mg 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 5 days before CgA

measurements (see section 5.1).

Pseudomembranous

colitis

been

reported

with

nearly

antibacterial

agents,

including

clarithromycin and amoxicillin, and may range in severity from mild to life threatening. Therefore, it is

important

consider

this

diagnosis

patients

present

with

diarrhea

subsequent

administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of

clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of

“antibiotic-associated colitis”.

After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should

be initiated. Mild cases of pseudomembranous colitis usually respond to discontinuation of the drug

alone. In moderate to severe cases, consideration should be given to management with fluids and

electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective

against Clostridium difficile colitis.

4.5

Interactions with other medicinal products and other forms of interaction

Interaction studies have only been performed in adults.

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, Cmax and 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, Cmax and Cmin by 36–39 % and mean AUC, Cmax and 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 and concomitant administration with

esomeprazole and nelfinavir is contraindicated.

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 metabolized by CYP2C19

Esomeprazole

inhibits

CYP2C19,

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

and AUC for cilostazol by 18% and 26%

respectively, and one of its active metabolites by 29% and 69% respectively.

Cisapride

In 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 a 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 drugs on the pharmacokinetics of esomeprazole

Medicinal products which inhibit CYP2C19 and/or CYP3A4

Esomeprazole

metabolised

CYP2C19

CYP3A4.

Concomitant

administration

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

by 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

NEXIUM,

clinical

data

exposed

pregnancies

insufficient. With

racemic

mixture

omeprazole data on a larger number of exposed pregnancies stemmed from epidemiological studies

indicate no malformative nor foetotoxic effects. 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).

Breast-feeding

It is not known whether esomeprazole is excreted in human breast milk. No studies in lactating women

have been performed. Therefore NEXIUM 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. No effects have been observed.

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.

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).

Blood and lymphatic system disorders

Rare: Leukopenia, thrombocytopenia

Very rare: Agranulocytosis, pancytopenia

Immune system disorders

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

Metabolism and nutrition disorders

Uncommon: Peripheral oedema

Rare: Hyponatraemia

Very Rare: Hypomagnesaemia ; severe hypomagnesaemia may result in hypocalcaemia.

Hypomagnesaemia may also result in hypokalaemia

Psychiatric disorders

Uncommon: Insomnia

Rare: Agitation, confusion, depression

Very rare: Aggression, hallucinations

Nervous system disorders

Common: Headache

Uncommon: Dizziness, paraesthesia, somnolence

Rare: Taste disturbance

Eye disorders

Rare: Blurred vision

Ear and labyrinth disorders

Uncommon: Vertigo

Respiratory, thoracic and mediastinal disorders

Rare: Bronchospasm

Gastrointestinal disorders

Common: Abdominal pain, constipation, diarrhoea, flatulence, nausea/vomiting

Uncommon: Dry mouth

Rare: Stomatitis, gastrointestinal candidiasis

Not known: Microscopic colitis

Hepatobiliary disorders

Uncommon: Increased liver enzymes

Rare: Hepatitis with or without jaundice

Very rare: Hepatic failure, encephalopathy in patients with pre-existing liver disease

Skin and subcutaneous tissue disorders

Uncommon: Dermatitis, pruritus, rash, urticarial

Rare: Alopecia, photosensitivity

Very rare: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN)

Not known:

Subacute cutaneous lupus erythematosus (see section 4.4)

Musculoskeletal, connective tissue and bone disorders

Uncommon: Fracture of the hip, wrist or spine

Rare: Arthralgia, myalgia

Very rare: Muscular weakness

Renal and urinary disorder

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

suspected

adverse

reactions

after

authorisation

medicinal

product

important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

Any suspected adverse events should be reported to the Ministry of Health according to the

National Regulation by using an online form

http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic

@moh.gov.il

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: 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 effectsAfter 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

GERD 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 esophagitis 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 Helicobacter pylori in approximately 90% of patients.

After

eradication

treatment

week

there

need

subsequent

monotherapy

with

antisecretory drugs for effective ulcer healing and symptom resolution in uncomplicated duodenal

ulcers.

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 Nexium 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 Nexium for 27 days for acid

suppression. The occurrence of rebleeding within 3 days was 5.9% in the Nexium treated group

compared to 10.3% for the placebo group. At 30 days post-treatment, the occurrence of rebleeding in

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

During treatment with antisecretory drugs serum gastrin increases in response to the decreased acid

secretion. Also 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.

If CgA and gastrin levels have not normalised after 5 days, measurements should be repeated 14 days

after cessation of esomeprazole treatment

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 a 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, Nexium showed better effect in healing of

gastric ulcers in patients using NSAIDs, including COX-2 selective NSAIDs.

In two studies with placebo as comparator, Nexium 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 GERD 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 enteric-coated 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

increases

after

repeated

once-daily

administration.

esomeprazole

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

about

after

single

dose

about

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.

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 lacks 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

implications

posology

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.

Elderly

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

Glycerol monostearate 40-55

hyprolose

hypromellose

iron oxide (20 mg & 40 mg tablets: reddish-brown; 20 mg tablets: yellow) (E 172)

magnesium stearate

methacrylic acid ethyl acrylate copolymer (1:1)

cellulose microcrystalline

synthetic paraffin

macrogols

polysorbate 80

crospovidone

sodium stearyl fumarate

sugar spheres*

talc

titanium dioxide (E 171)

triethyl citrate.

* Sugar spheres content in NEXIUM 20 mg: 28 mg

* Sugar spheres content in NEXIUM 40 mg: 30 mg

6.2

Incompatibilities

Not applicable

6.3

Special precautions for storage

Do not store above 30°C

Store in the original package (blister) in order to protect from moisture.

6.4

Presentation

20 mg: Packs of 7, 14, and 28 tablets.

40 mg: Packs of 7, and 28 tablets.

6.6

Instructions for use and handling

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 for approximately 2 minutes to disperse the tablet.

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.

7

Registration Numbers

NEXIUM 20 mg tablets: 122 52 30237 00/11

NEXIUM 40 mg tablets: 122 53 30238 00/11

8

Manufacturer

AstraZeneca AB., Sweden

9

License Holder

Astrazeneca (Israel) Ltd.

POB 1455 Hod Hasharon 4524075

REFERENCES

Hasselgren B and Mellander-Dahlberg A

NEXIUM

AXANUM

VIMOVO

Clinical Overview on potential interaction with tacrolimus

[GI.000-216-506.2.0] February 2012

Hasselgren B, Mellander-Dahlberg A and Philip A

LOSEC

, NEXIUM

AXANUM

VIMOVO

Clinical Overview on hypocalcaemia in connection with hypomagnesaemia

[GI.000-216-505.2.0] February 2012

Philip A, Hasselgren B and Mellander-Dahlberg A

LOSEC

, NEXIUM

, AXANUM

VIMOVO

Clinical Overview on Chromogranin A

[GI.000-216-503.2.0] February 2012

Hasselgren B, Mellander-Dahlberg A and Philip A

LOSEC

, NEXIUM

AXANUM

VIMOVO

Clinical Overview on Enterochromaffin cell-like (ECL) hyperplasia

[GI.000-216-504.2.0] February 2012

לע העדוה לע העדוה לע העדוה ( הרמחה ( הרמחה ( הרמחה

עדימ עדימ עדימ ל ןולעב )תוחיטב ל ןולעב )תוחיטב ל ןולעב )תוחיטב אפור אפור אפור

ןכדועמ( ןכדועמ( ןכדועמ(

.102.50

.102.50

.102.50

ךיראת

78.8.7

תילגנאב רישכת םש

םושירה רפסמו

-

NEXIUM 20 mg tablets: 122 52 30237 00/11

NEXIUM 40 mg tablets: 122 53 30238 00/11

_________________________________לארשי הקינזהרטסא_ םושירה לעב םש ה טורפל דעוימ הז ספוט דבלב תורמחה

תושקובמה תורמחהה

ןולעב קרפ

יחכונ טסקט

שדח טסקט

4.4 Special Warnings

and Special

Precautions for Use

Adverse events

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 5 days before CgA

measurements (see section

5.1).

ל תוחיכשה התנוש

KNOWN

ןוכדיע ינפל . תוחיכשה התיה

very rare

םייק אל

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 5 days before CgA measurements (see section 5.1).

If CgA and gastrin levels have not returned to reference

range after initial measurement, measurements should be

repeated 14 days after cessation of proton pump inhibitor

treatment.

Metabolism and nutrition disorders – not known -

Hypomagnesaemia (see section 4.4); severe

hypomagnesaemia can correlate with hypocalcaemia.

Hypomagnesaemia may also be associated with

hypokalaemia.

Gastrointestinal disorders – common - fundic gland polyps

ה

ה

ה

לע העדו לע העדו לע העדו ( הרמחה ( הרמחה ( הרמחה

עדימ עדימ עדימ ןכרצל ןולעב )תוחיטב ןכרצל ןולעב )תוחיטב ןכרצל ןולעב )תוחיטב

ןכדועמ( ןכדועמ( ןכדועמ(

.102.50

.102.50

.102.50

ךיראת

78.8.7

םושירה רפסמו תילגנאב רישכת םש

:

םושירה רפסמו תילגנאב רישכת םש

-

NEXIUM 20 mg tablets: 122 52 30237 00/11

NEXIUM 40 mg tablets: 122 53 30238 00/11

םושירה לעב םש

:

AstraZeneca Israel

ה טורפל דעוימ הז ספוט דבלב תורמחה

תושקובמה תורמחהה

פ

ןולעב קר

יחכונ טסקט

שדח טסקט

תודחוימ תורהזא שומישל תועגונה םויסקנב

םייק אל

תקידב עצבל דמוע התא םא םד ןינרגומורכ( תמיוסמ

Chromogranin

יאוול תועפות

םד יאתב הדירי( םד תריפסב םייוניש )םינבל

םייק אל

םד תריפסב םייוניש סיזוטיצולונרגא ללוכ ,

רי( )םינבל םד יאתב הדי

םיקרפמ יבאכ םע בולישב ללכ ךרדב ,החירפ

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