Package Insert: Information for the User

Nexium 40 mg Powder for Injection and for Infusion

esomeprazole

Read this package insert carefully before starting to use this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

Nexiumcontains a medication called esomeprazole that belongs to a group of medications called “proton pump inhibitors”. These work by reducing the amount of acid produced by the stomach.

Nexiumis used for the treatment of the following disorders, when oral treatment is not possible:

Adults

• Gastroesophageal reflux disease (GERD). This occurs when stomach acid rises up the esophagus (the tube that goes from the throat to the stomach) producing pain, inflammation, and burning.
• Stomach ulcers caused by medications called nonsteroidal anti-inflammatory drugs (NSAIDs). Nexium may also be used to prevent the formation of ulcers if you are taking NSAIDs.
• Prevention of bleeding after a therapeutic endoscopy performed in case of acute bleeding due to gastric or duodenal ulcer.

Children and adolescents aged 1 to 18 years

• Gastroesophageal reflux disease (GERD). This occurs when stomach acid rises up the esophagus (the tube that goes from the throat to the stomach) producing pain, inflammation, and burning.

Do not administer Nexium

• if you are allergic to esomeprazole or any of the other ingredients of this medication (listed in section 6).
• if you are allergic toother proton pump inhibitors(e.g. pantoprazole, lansoprazole, rabeprazole, omeprazole).
• if you are taking a medication that contains nelfinavir (used in the treatment of HIV infection).

If you are in any of these situations, Nexium will not be administered to you. If you are unsure, consult your doctor, pharmacist or nurse before this medication is administered to you.

Warnings and precautions

Consult your doctor or nurse before Nexium is administered to you if:

• You have severe liver problems.
• You have severe kidney problems.
• You have had a skin reaction after treatment with a similar medication to Nexium for reducing stomach acid.
• You are scheduled to have a specific blood test (Cromogranin A).

Nexium may mask symptoms of other diseases.Therefore, if you observe any of the following events before Nexium is administered to you or after its administration, contact your doctor immediately:

• You lose a lot of weight without reason and have trouble swallowing.
• You experience stomach pain or indigestion.
• You begin to vomit food or blood.
• Your stools appear black (blood-stained).

Taking a proton pump inhibitor like Nexium, especially for more than a year, may slightly increase the risk of breaking a hip, wrist or spine. Inform your doctor if you have osteoporosis or are taking corticosteroids (which may increase the risk of osteoporosis).

Rashes and skin symptoms

If you experience a rash, especially on sun-exposed skin areas, consult your doctor as soon as possible, as it may be necessary to interrupt Nexium treatment. Remember to mention any other symptoms you may notice, such as joint pain.

Severe skin rashes have occurred in patients taking esomeprazole (see also section 4). The rash may include mouth ulcers, throat, nose, genital, and conjunctivitis (red and swollen eyes). These severe skin rashes usually appear after symptoms similar to the flu, such as fever, headache, and body aches. The rash may cover large areas of the body with blisters and skin peeling.

If, at any time during treatment (even after several weeks), you develop a rash or any of these skin symptoms, stop taking this medication and contact your doctor immediately.

Use of Nexium with other medications

Inform your doctor or nurse if you are taking, have taken recently, or may need to take any other medication. This includes medications purchased without a prescription. This is because Nexium may affect how some medications work and some medications may influence the effect of Nexium.

Nexium will not be administered to you if you are taking a medication that contains nelfinavir (used for HIV infection).

Inform your doctor if you are using any of the following medications:

• Atazanavir (used for HIV infection).
• Clopidogrel (used to prevent blood clots).
• Ketoconazole, itraconazole, or voriconazole (for fungal infections).
• Erlotinib (used in cancer treatment).
• Citalopram, imipramine, clomipramine (for depression treatment).
• Diazepam (used for anxiety, muscle relaxation, or epilepsy).
• Phenytoin (for epilepsy). If you are taking phenytoin, your doctor will need to monitor when you start or stop taking Nexium.
• Medications used to make blood thinner, such as warfarin. Your doctor may need to monitor when you start or stop taking Nexium.
• Cilostazol (used for intermittent claudication – leg pain caused by poor blood circulation).
• Cisapride (used for indigestion and heartburn).
• Digoxin (used for heart problems).
• Methotrexate (chemotherapy medication used at high doses for cancer treatment) – if you are taking high doses of methotrexate, your doctor may temporarily interrupt your Nexium treatment.
• Tacrolimus (organ transplant).
• Rifampicin (used for tuberculosis treatment).
• St. John's Wort (Hypericum perforatum) (used to treat depression).

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before this medication is administered to you. Your doctor will decide if Nexium can be administered to you during this period.

The passage of Nexium into breast milk is unknown. Therefore, do not take Nexium during breastfeeding.

Driving and operating machinery

Nexium is unlikely to affect your ability to drive or use tools or machines. However, rare side effects such as dizziness or blurred vision (see section 4) may occur. Do not drive or use machines if you notice any of these side effects.

Nexiumcan be administered to children and adolescents from 1 to 18years and to adults, including elderly patients.

Nexium Administration

Use in Adults

• Nexiumwill be administered by your doctor who will decide the dose you need.
• The recommended dose is 20mg or 40mg once a day.
• If you have severe liver problems, the maximum dose is 20mg per day (ERGE).
• The medication will be administered as an injection or as an infusion into one of your veins. This will last up to 30 minutes.
• The recommended dose for the prevention of bleeding due to gastric or duodenal ulcer is 80mg administered as an intravenous infusion for 30minutes followed by 8mg/h as a continuous infusion for 3days. If you have severe liver problems, 4mg/h as a continuous infusion for 3days may be sufficient.

Use in Children and Adolescents

• Nexium will be administered by your doctor who will decide the dose you need.
• For children from 1 to 11years, the recommended dose is 10 or 20mg once a day.
• For children from 12 to 18years, the recommended dose is 20 or 40mg once a day.
• The medication will be administered as an injection or as an infusion into one of your veins. This will last up to 30minutes.

If You Are Given More Nexium Than You Should

If you think you have been given too much Nexium, consult your doctor immediately.

In case of overdose or accidental ingestion, contact the Toxicology Information Service. Phone 91 5620420, indicating the medication and the amount administered.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

If you notice any of the following serious side effects, stop taking Nexium and contact a doctor immediately:

• Yellow skin, dark urine, and fatigue that may be symptoms of liver problems.

These side effects are rare and may affect up to 1 in 1,000 people.

• Sudden difficulty breathing, swelling of the lips, tongue, and throat or body in general, skin rash, fainting, or difficulty swallowing (severe allergic reaction).

These side effects are rare and may affect up to 1 in 1,000 people.

• Sudden appearance of a severe skin rash or redness of the skin with blisters or peeling, even after several weeks of treatment. Blisters may also appear and bleeding from the lips, eyes, mouth, nose, and genitals may occur. Skin rashes may become severe and widespread skin damage (peeling of the epidermis and superficial mucous membranes) with potentially fatal consequences. It may be a "multiforme erythema", "Stevens-Johnson syndrome", "toxic epidermal necrolysis", or "drug reaction with eosinophilia and systemic symptoms".

These side effects are very rare and may affect up to 1 in 10,000 people.

Other side effects include:

Frequent (may affect up to 1 in 10 people)

• Headache.
• Effects on the stomach or intestine: stomach pain, constipation, diarrhea, gas (flatulence).
• Nausea or vomiting.
• Reaction at the injection site.
• Benign polyps in the stomach.

Occasional (may affect up to 1 in 100 people)

• Swelling of the feet and ankles.
• Insomnia (sleep disturbance).
• Dizziness, tingling, and numbness, somnolence.
• Eye disorders such as blurred vision.
• Dizziness.
• Dry mouth.
• Alteration of blood tests that determine liver function.
• Skin rash, urticaria, itching skin.
• Fracture of the hip, wrist, or spine (if Nexium is used at high doses and for a long period).

Rare (may affect up to 1 in 1,000 people)

• Blood disorders such as a decrease in the number of white blood cells or platelets. This may cause weakness, bruising, or increase the risk of infections.
• Low sodium levels in the blood. This may cause weakness, vomiting, and muscle cramps.
• Agitation, confusion, or depression.
• Alteration of taste.
• Sudden feeling of lack of air or difficulty breathing (bronchospasm).
• Inflammation in the interior of the mouth.
• A known infection called "candidiasis" that may affect the esophagus and is caused by a fungus.
• Liver problems including jaundice that may cause yellow skin, dark urine, and fatigue.
• Hair loss (alopecia).
• Dermatitis caused by exposure to sunlight.
• Joint pain (arthralgia) or muscle pain (myalgia).
• General feeling of discomfort and lack of energy.
• Increased sweating.

Very rare (may affect up to 1 in 10,000 people)

• Changes in the number of cells in the blood, including agranulocytosis (decrease in the number of white blood cells).
• Aggression.
• To see, feel, or hear things that do not exist (hallucinations).
• Liver disorders that may lead to liver failure or brain inflammation.
• Sudden appearance of severe skin rash, blisters, or peeling of the skin. These symptoms may be accompanied by high fever and joint pain (Erythema multiforme, Stevens-Johnson syndrome, Toxic epidermal necrolysis, Drug reaction with eosinophilia and systemic symptoms).
• Muscle weakness.
• Severe kidney disorders.
• Increased breast size in men.

Frequency not known (the frequency cannot be estimated from the available data)

• If you are being treated with Nexium for more than three months, it is possible that your magnesium levels in the blood will decrease. Low magnesium levels may manifest as fatigue, involuntary muscle contractions, disorientation, seizures, dizziness, or increased heart rate. If you experience any of these symptoms, inform your doctor immediately. Low magnesium levels may 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 magnesium levels.

• Inflammation in the intestine (may cause diarrhea).
• Skin rash, possibly with joint pain.

In rare cases, Nexium may affect white blood cells, causing immunodeficiency. If you have an infection with symptoms such as severe worsening of the general condition or fever with symptoms of a local infection such as neck pain, throat pain, mouth pain, or difficulty urinating, you should consult your doctor as soon as possible to rule out a decrease in the number of white blood cells (agranulocytosis) through a blood test. It is essential to inform your doctor about your medication in this case.

Reporting side effects

If you experience any type of side effect, consult your doctor, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through theSistema Español de Farmacovigilancia de medicamentos de Uso Humano:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

• Keep this medication out of the sight and reach of children.
• The doctor and hospital pharmacist are responsible for the proper conservation, handling, and disposal of Nexium.
• Do not use this medication after the expiration date that appears on the packaging and vial after EXP. The expiration date is the last day of the month indicated.
• Do not store above 86°F (30°C).

Store the vial in the outer packaging to protect it from light. However, vials may be stored outside the packaging exposed to interior light for up to 24 hours.

Composition of Nexium

• The active ingredient is esomeprazole sodium. Each vial of powder for injectable solution and for infusion contains 42.5mg of esomeprazole sodium, equivalent to 40mg of esomeprazole.

• The other components areedetate disodium and sodium hydroxide.This medicine contains less than 23mg (1mmol) of sodium per vial, so it is considered essentially “sodium-free”.

Aspect of the product and content of the package

Nexium is a porous or white to off-white powder. Before it is administered, this is reconstituted into a solution.

Packages: 1 vial, 10 vials.It may only be marketed in some package sizes.

Holder of the marketing authorization and responsible for the manufacture

Holder of the marketing authorization:

Grünenthal Pharma, S.A.

Doctor Zamenhof, 36 – 28027 Madrid, Spain

Responsible for the manufacture

AstraZeneca AB,152 57Södertälje, Sweden

Grünenthal GmbH, Zieglerstrasse 6- D- 52078 Aachen, Germany

This medicine is authorized in the member states of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Last review date of this leaflet: December 2021

Other sources of information

The detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/.

This information is intended solely for healthcare professionals:

Nexium 40mg contains 40mg of esomeprazole, as sodium salt. Each vial also contains edetate disodium and sodium hydroxide (<1mmol of sodium).

The vials are for single use. If the unused solution from the reconstituted vial is not used for a single dose, it must be discarded.

For further information on dosage recommendations and storage conditions, please refer to sections 3 and 5, respectively.

Preparation and administration of the reconstituted solution:

To reconstitute the solution, remove the plastic cap from the top of the Nexium vial and pierce the stopper in the center of the marked circle, keeping the needle in a vertical position, in order to be able to correctly pierce the stopper.

The reconstituted solution for injection or infusion must be transparent and colorless to slightly yellow. It must be visually inspected to detect particles and discoloration before administration and only the transparent solution should be used.

The stability has been demonstrated in terms of physical and chemical stability for 12 hours at 30°C. However, from a microbiological point of view, the product should be used immediately.

Injection of Nexium

For preparing a solution for injection:

Injection of 40mg

To a reconstituted solution of 8mg/ml of esomeprazole: Prepare the solution by adding 5ml of sodium chloride 0.9% for intravenous use to the vial of esomeprazole 40mg.

The reconstituted solution for injection must be administered intravenously over a period of at least 3 minutes.

For further information on the administration of the doses, please refer to the technical data sheet, section 4.2.

Infusion of Nexium

For preparing a solution for infusion:

Infusion 40mg

Dissolve the contents of a vial of esomeprazole 40mg in up to 100ml of sodium chloride 0.9% for intravenous use.

Infusion 80mg

Dissolve the contents of two vials of esomeprazole 40mg in up to 100mlof sodium chloride 0.9% for intravenous use.

For further information on the administration of the dose, please refer to the technical data sheet, section 4.2.

Elimination

Any remaining medicine or waste material should be disposed of in accordance with local procedures.