Prospect: information for the patient

Esomeprazol Combix 40 mg gastro-resistant tablets EFG

Read this prospect carefully before starting to take this medicine, because it contains important information for you.

-Keep this prospect, as you may need to read it again.

-If you have any doubts, consult your doctor or pharmacist.

-This medicine has been prescribed only for you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.

-If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section 4.

1. What isEsomeprazol Combixand for what it is used

2. What you need to know before starting to takeEsomeprazol Combix

3. How to takeEsomeprazol Combix

4. Possible adverse effects

5. Storage ofEsomeprazol Combix

6. Contents of the package and additional information

Esomeprazol Combix contains a medicine called esomeprazole that belongs to a group of medicines called “proton pump inhibitors”. These work by reducing the amount of acid produced by the stomach.

Esomeprazole is used to treat the following conditions:

Adults

• Gastroesophageal reflux disease (GERD). This occurs when stomach acid rises up into the esophagus (the tube that goes from the throat to the stomach) causing pain, inflammation, and burning.
• Excessive stomach acid produced by a tumor in the pancreas (Zollinger-Ellison syndrome).
• Continuation treatment for the prevention of bleeding from a peptic ulcer induced with esomeprazole intravenously.

Adolescents 12 years of age and older

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

Do not take Esomeprazol Combix

• if you are allergic to esomeprazole or any of the other ingredients in this medicine (listed in section 6).
• if you are allergic to other medicines in the group of proton pump inhibitors (e.g. pantoprazole, lansoprazole, rabeprazole, omeprazole).
• if you are taking a medicine that contains nelfinavir (used in the treatment of HIV infection).
• if you have ever developed a severe skin rash or skin peeling, blistering or ulcers in the mouth after taking esomeprazole or other related medicines.

If you are in any of these situations, do not take esomeprazole. If you are unsure, consult your doctor or pharmacist before taking esomeprazole.

Warnings and precautions

Consult your doctor or pharmacist before starting to take esomeprazole:

• if you have severe liver problems.
• if you have severe kidney problems.
• if you have ever had a skin reaction after treatment with a similar medicine to esomeprazole for reducing stomach acid.
• if you are due to have a specific blood test (Cromogranin A).

Esomeprazole may mask the symptoms of other diseases.Therefore, if you notice any of the following events before taking or while taking esomeprazole, contact your doctor immediately:

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

If your doctor has prescribed esomeprazole only when you notice some symptoms, you should contact your doctor if the symptoms of your disease persist or change.

Taking a proton pump inhibitor like esomeprazole, 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 if you are taking corticosteroids (which may increase the risk of osteoporosis).

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

Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported in relation to treatment with esomeprazole. Stop taking esomeprazole and seek medical attention immediately if you notice any of the symptoms related to these severe skin reactions described in section 4.

Children under 12 years

The information on dosing for children aged 1 to 11 years is presented in the product information for esomeprazole in sachets (consult your doctor or pharmacist if you need additional information).

Other medicines and Esomeprazol Combix

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medicine. This includes medicines bought without a prescription. This is because esomeprazole may affect the way some medicines work and some medicines may influence the effect of esomeprazole.

Do not take esomeprazole if you are taking a medicine that contains nelfinavir (used for the treatment of HIV infection).

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

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

If your doctor has prescribed the antibiotics amoxicillin and clarithromycin in addition to esomeprazole to treat ulcers caused byHelicobacter pylori, it is very important to inform your doctor if you are taking any other medicine.

Taking Esomeprazol Combix with food and drinks

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

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or are planning to become pregnant, consult your doctor or pharmacist before using this medicine. Your doctor will decide if you can take esomeprazole during this period.

The safety of esomeprazole for use during pregnancy has not been established. Therefore, esomeprazole should not be taken during pregnancy.

Driving and using machines

Esomeprazole is unlikely to affect your ability to drive or use tools or machines.However, rare or very 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.

Esomeprazol Combix contains saccharose.

Esomeprazole contains sugar spheres that contain saccharose, a type of sugar. If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medicine.

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

• If you take this medication for a long period of time, your doctor will need to monitor you (especially if you take it for more than a year).
• If your doctor has told you to take this medication only when you notice some symptoms, inform your doctor if the symptoms change.

How much to take

• Your doctor will have indicated how many tablets you should take and when to take them. This will depend on your situation, age, and liver function.
• The recommended doses are indicated below:

Use in adults aged 18 years and older

For the treatment of heartburn caused by gastroesophageal reflux disease (GERD):

• If your doctor has determined that your esophagus is slightly affected, the recommended dose is one 40 mg gastro-resistant tablet of esomeprazole once a day for 4 weeks. Your doctor may indicate that you take the same dose for another 4 weeks if your esophagus has not yet healed.
• If you have severe liver problems, your doctor may prescribe a lower dose.

For the treatment of excessive stomach acid caused by a tumor in the pancreas (Zollinger-Ellison syndrome):

• The recommended dose is one 40 mg gastro-resistant tablet of esomeprazole twice a day.
• Your doctor will adjust the dose according to your needs and also decide for how long you should take this medication. The maximum dose is 80 mg twice a day.

Continuation treatment for the prevention of bleeding from peptic ulcer induced with esomeprazole intravenously:

• The recommended dose is one 40 mg gastro-resistant tablet of esomeprazole once a day for 4 weeks.

Use in adolescents aged 12 years and older

For the treatment of heartburn caused by gastroesophageal reflux disease (GERD):

• If your doctor has determined that your esophagus is slightly affected, the recommended dose is one 40 mg gastro-resistant tablet of esomeprazole once a day for 4 weeks. Your doctor may indicate that you take the same dose for another 4 weeks if your esophagus has not yet healed.
• If you have severe liver problems, your doctor may prescribe a lower dose.

How to take this medication

• You can take the tablets at any time of the day.
• You can take the tablets with food or on an empty stomach.
• Swallow the tablets whole with a glass of water. Do not chew or crush the tablets. This is because the tablets contain coated granules that prevent the medication from being destroyed by stomach acid. It is essential not to damage the granules.

What to do if you have difficulty swallowing

• If you have difficulty swallowing the tablets:

• Put the tablets in a glass of water without gas. Do not use other liquids.
• Stir until the tablets disintegrate (the solution will not be transparent). You can drink the mixture immediately or within 30 minutes. Stir always just before drinking.
• To ensure that you have taken all the medication, rinse the glass well with half a glass of water and drink. The solid particles contain the medication – do not chew or crush the granules.

• If you cannot swallow at all, the tablets can be dispersed in water and introduced into a syringe. They can then be administered directly into the stomach through a tube (gastric tube).

Use in children under 12 years of age

Esomeprazole is not recommended for children under 12 years of age.

The information on dosing for children aged 1 to 11 years is presented in the product information for esomeprazole in sachets (consult your doctor or pharmacist if you need additional information).

Older adults

No dose adjustment is necessary for older adults.

If you take more Esomeprazol Combix than you should

If you take more esomeprazole than your doctor has indicated, consult your doctor or pharmacist immediately.

In case of overdose or accidental ingestion, you can also call the Toxicological Information Service, Tel. 91 562 04 20, indicating the medication and the amount taken. You will be advised to bring the packaging and the medication leaflet to the healthcare professional.

If you forget to take Esomeprazol Combix

• If you forget to take a dose, take it as soon as you remember. However, if it is almost time for your next dose, do not take the missed dose.
• Do not take a double dose to compensate for the missed doses.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

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

If you notice any of the following serious side effects, stop takingEsomeprazol Combixand contact a doctor immediately:

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

• Redness of the skin with blisters or peeling. Large blisters and bleeding from the lips, eyes, mouth, nose, and genitals may also occur. This could be a "Stevens-Johnson syndrome" or "toxic epidermal necrolysis."
• Yellow skin, dark urine, and fatigue, which may be symptoms of liver problems.
• Widespread rash, high body temperature, and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome), which is very rare.

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

Other side effects include:

Frequent (may affect up to 1 in 10 people)

• Headache.
• Effects on the stomach or intestines: stomach pain, constipation, diarrhea, gas (flatulence).
• Nausea or vomiting.
• Benign stomach polyps.

Occasional (may affect up to 1 in 100 people)

• Swelling of the feet and ankles.
• Sleep disturbance (insomnia).
• Dizziness, tingling, and numbness, drowsiness.
• Vertigo.
• Dry mouth.
• Abnormal blood test results indicating liver function.
• Rash, urticaria, itching skin.
• Fracture of the hip, wrist, or spine (if Esomeprazol Combix 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 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.
• Restlessness, confusion, or depression.
• Altered taste.
• Eye disorders such as blurred vision.
• Sudden feeling of lack of air or difficulty breathing (bronchospasm).
• Inflammation in the interior of the mouth.
• A fungal infection known as "candidiasis" that may affect the esophagus.
• Liver problems including jaundice, which 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 blood cells, including agranulocytosis (decrease in white blood cells).
• Aggression.
• Seeing, feeling, or hearing 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).
• Muscle weakness.
• Severe kidney disorders.
• Enlargement of the breasts in men.

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

• If you are being treated withEsomeprazol Combixfor 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 tests to monitor your magnesium levels.

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

In rare cases, esomeprazole may affect white blood cells, leading to immunodeficiency.

If you have an infection with symptoms such as high fever and 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 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 or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keepthis medicationout of the sight and reach of children.

Do not store at a temperature above 25°C.

Store in the original packaging to protect it from moisture.

Do not usethis medicationafter the expiration date that appears onthe packaging after CAD.The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGREpoint at the pharmacy. Ask your pharmacist how to dispose of packaging and medications you no longer need. By doing so, you will help protect the environment.

Esomeprazol Combix Composition

• The active ingredient is esomeprazole. Each gastro-resistant tablet contains 40 mg of esomeprazole (as esomeprazole magnesium dihydrate).
• The other components are:

Tablet Core: sugar spheres (sucrose and cornstarch), hydroxypropylcellulose (E463), light magnesium oxide (E530).

Coating:povidone K-30, mannitol (E421), magnesium stearate (vegetal) (E470b), copolymer of methacrylic acid and ethyl acrylate, polysorbate 80 (E433), triethyl citrate (E1507), mono- and diglycerides of fatty acids (E472a), hypromellose, macrogol 8000, microcrystalline cellulose (E460i), crospovidone (type A), copovidone, talc, opadry rosa 20A54019 (a compound consisting of hypromellose, hydroxypropylcellulose (E463), titanium dioxide (E171), talc, and iron oxide red (E172)).

Product Appearance and Packaging Contents

Pink, oval, biconvex, bisected tablets with a film coating, with the imprint “40” on one face and smooth on the other.

Esomeprazol Combix 40 mg is presented in blisters with desiccant OPA/Al/PE-PE/Al, available in packs of 14, 28, and 56 tablets.

Only some pack sizes may be marketed.

Marketing Authorization Holder and Responsible Manufacturer

Marketing Authorization Holder:

Combix Laboratories, S.L.U.

C/ Badajoz 2, Edificio 2.

28223 Pozuelo de Alarcón (Madrid)

Spain

Responsible Manufacturer:

Zydus France

ZAC Les Hautes Patures

Parc d'activités des Peupliers

25 Rue des Peupliers

92000 Nanterre

France

or

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 Rue de la Chapelle

63450 Saint Amant Tallende

France

or

Netpharmalab Consulting Services

Carretera de Fuencarral 22,

Alcobendas,

28108 Madrid

Spain

or

Flavine Pharma France

3 Voie d’Allemagne

13127 Vitrolles

France

Last Review Date of this Leaflet: February 2025

Other Sources of Information

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:

Administration via gastric tube

1. Insert the tablet into a suitable syringe and fill the syringe with approximately 25 ml of water and approximately 5 ml of air. For some tubes, a dispersion in 50 ml of water is required to prevent the pellets from blocking the tube.

2. Shake the syringe immediately for approximately 2 minutes to disperse the tablet.

3. Hold the syringe with the tip pointing upwards and check that the tip has not become blocked.

4. Connect the syringe to the tube while maintaining the previous position.

5. Shake the syringe and place it with the tip pointing downwards. Inject immediately 5-10 ml into the tube. Invert the syringe after injection and shake (the syringe must be kept with the tip pointing upwards to prevent the tip from becoming blocked).

6. Place the syringe with the tip pointing downwards and inject immediately another 5-10 ml into the tube. Repeat this procedure until the syringe is empty.

7. Fill the syringe with 25 ml of water and 5 ml of air and repeat step 5 if necessary to draw any sediment remaining in the syringe. For some tubes, 50 ml of water is required.