ESOMEPRAZOL COMBIX 40 mg GASTRO-RESISTANT TABLETS

2. What you need to know before you take Esomeprazol Combix

Do not take Esomeprazol Combix

• if you are allergic to esomeprazol or any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to other medicines of the same group (e.g. pantoprazole, lansoprazole, rabeprazole, omeprazol).
• if you are taking a medicine that contains nelfinavir (used to treat HIV infection).
• if you have ever developed a severe skin rash or blistering of the skin, or peeling of the skin and mucous membranes after taking esomeprazol or other medicines of the same group.

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

Warnings and precautions

Consult your doctor or pharmacist before starting to take esomeprazol:

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

Esomeprazol may mask the symptoms of other diseases. Therefore, if you notice any of the following events before or while taking esomeprazol, 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 (stained with blood).

If you have been prescribed esomeprazol only when you notice symptoms, you should contact your doctor if the symptoms of your disease persist or change.

Taking a proton pump inhibitor like esomeprazol, especially for more than one year, may slightly increase the risk of hip, wrist, or spine fractures.

Tell your doctor if you have osteoporosis or if you are taking corticosteroids (which can increase the risk of osteoporosis).

If you get a skin rash, especially in areas of the skin exposed to the sun, contact your doctor as soon as possible, as it may be necessary to stop treatment with esomeprazol. 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 esomeprazol. Stop taking esomeprazol and seek immediate medical attention if you notice any of the symptoms related to these severe skin reactions described in section 4.

Children under 12 years of age

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

Other medicines and Esomeprazol Combix

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes medicines obtained without a prescription. This is because esomeprazol may affect how some medicines work and some medicines may affect the effect of esomeprazol.

Do not take esomeprazol if you are taking a medicine that contains nelfinavir(used to treat HIV infection).

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

• Atazanavir (used to treat 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).
• Diazepam (used for anxiety, as a muscle relaxant, or for epilepsy).
• Phenytoin (for epilepsy). If you are taking phenytoin, your doctor will need to monitor when you start or stop taking Esomeprazol Combix.
• Medicines used to make blood more fluid, such as warfarin. Your doctor may need to monitor when you start or stop taking Esomeprazol Combix.
• Cilostazol (used to treat intermittent claudication – leg pain when walking caused by insufficient blood pumping).
• Cisapride (used for indigestion and heartburn).
• Digoxin (used for heart problems).
• Methotrexate (chemotherapy medicine used at high doses in cancer treatment) – if you are taking high doses of methotrexate, your doctor may temporarily stop your treatment with Esomeprazol Combix.
• Tacrolimus (organ transplant).
• Rifampicin (used to treat tuberculosis).
• St. John's Wort (Hypericum perforatum) (used to treat depression).

If your doctor has prescribed the antibiotics amoxicillin and clarithromycin along with esomeprazol to treat ulcers caused by Helicobacter pylori, it is very important that you 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, breast-feeding, and fertility

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Your doctor will decide whether you can take esomeprazol during this time.

It is not known if esomeprazol passes into breast milk. Therefore, you should not take esomeprazol during breast-feeding.

Driving and using machines

Esomeprazol is unlikely to affect your ability to drive or use tools or machines. However, sometimes 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 effects.

Esomeprazol Combix contains sucrose.

Esomeprazol contains sugar spheres that contain sucrose, a type of sugar. If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Esomeprazol Combix

Follow the instructions for administration of this medicine exactly as told by your doctor or pharmacist. If you are not sure, consult your doctor or pharmacist again.

• If you take this medicine for a long 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 medicine only when you notice symptoms, inform your doctor if the symptoms change.

How much to take

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

Use in adults from 18 years of age

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

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

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

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

Continuation treatment for the prevention of rebleeding from peptic ulcers induced with esomeprazol intravenously:

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

Use in adolescents from 12 years of age

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

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

Taking this medicine

• 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 medicine from being destroyed by the acid in the stomach. It is important 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 break up (the solution will not be clear). You can drink the mixture immediately or within 30 minutes. Always stir just before drinking.
• To make sure you have taken all the medicine, rinse the glass well with half a glass of water and drink. The solid particles contain the medicine – 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

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

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

Elderly patients

No dose adjustment is necessary in elderly patients.

If you take more Esomeprazol Combix than you should

If you take more esomeprazol than your doctor has told you, contact your doctor or pharmacist immediately.

In case of overdose or accidental ingestion, you can also call the Toxicology Information Service, Telephone 91 562 04 20, indicating the medicine and the amount taken. It is recommended to take the packaging and the leaflet of the medicine 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 make up for forgotten doses.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

If you observe any of the following serious adverse effects, stop taking Esomeprazol Combix and contact a doctor immediately:

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

• Redness of the skin with blisters or peeling. Large blisters and bleeding of the lips, eyes, mouth, nose, and genitals may also appear. This could be a "Stevens-Johnson Syndrome" or "toxic epidermal necrolysis".
• Yellow skin, dark urine, and fatigue that can 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 effects are rare and may affect up to 1 in 1,000 people.

Other adverse 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.
• Benign polyps in the stomach.

Infrequent (may affect up to 1 in 100 people)

• Swelling of feet and ankles.
• Sleep disturbance (insomnia).
• Dizziness, tingling, and numbness, drowsiness.
• Vertigo sensation.
• Dry mouth.
• Alteration of blood tests that determine liver function.
• Skin rash, hives, itching of the 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 the number of white blood cells or platelets. This can cause weakness, bruising, or increase the likelihood of infections.
• Low sodium levels in the blood. This can cause weakness, vomiting, and cramps.
• Agitation, confusion, or depression.
• Taste alteration.
• Eye disorders such as blurred vision.
• Sudden shortness of breath or difficulty breathing (bronchospasm).
• Inflammation inside the mouth.
• An infection known as "candidiasis" that can affect the esophagus and is caused by a fungus.
• Liver problems including jaundice that can cause yellow skin, dark urine, and fatigue.
• Hair loss (alopecia).
• Dermatitis due to sun exposure.
• 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).
• Aggressiveness.
• Seeing, feeling, or hearing things that do not exist (hallucinations).
• Liver disorders that can lead to liver failure or brain inflammation.
• Sudden appearance of severe skin rash, blisters, or peeling of the skin. These symptoms can 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 (frequency cannot be estimated from available data)

• If you are being treated with Esomeprazol Combix for more than three months, it is possible that your magnesium levels in the blood may decrease. Low magnesium levels can manifest as fatigue, involuntary muscle contractions, disorientation, convulsions, dizziness, or increased heart rate. If you have any of these symptoms, inform your doctor immediately. Low magnesium levels can also lead to a reduction in potassium or calcium levels in the blood.

Your doctor may decide to perform periodic tests to monitor your magnesium levels.

• Inflammation in the intestine (can lead to diarrhea).
• Skin rash, possibly with joint pain.

In very rare cases, esomeprazol can affect white blood cells, causing an immune deficiency.

If you have an infection with symptoms such as fever with a severe worsening of your general condition or fever with symptoms of a local infection such as pain in the neck, throat, mouth, 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 that, in this case, you inform about your medication.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Conservation of Esomeprazol Combix

Keep this medicine out of sight and reach of children.

Do not store at a temperature above 25°C.

Keep in the original packaging to protect it from moisture.

Do not use this medicine after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Medicines should not be thrown away through drains or waste. Deposit the packaging and medicines you no longer need at the pharmacy's SIGRE point. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Esomeprazol Combix

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

Core of the tablet: sugar spheres (sucrose and corn starch), hydroxypropylcellulose (E463), light magnesium oxide (E530).

Coating: povidone K-30, mannitol (E421), magnesium stearate (vegetable) (E470b), methacrylic acid - ethyl acrylate copolymer, polysorbate 80 (E433), triethyl citrate (E1507), glycerol monostearate 40-55 (E472a), hypromellose, macrogol 8000, silicified microcrystalline cellulose (E460i), microcrystalline cellulose (E460i), crospovidone (type A), copovidone, talc, opadry pink 20A54019 (composed of hypromellose, hydroxypropylcellulose (E463), titanium dioxide (E171), talc, and red iron oxide (E172)).

Appearance of the Product and Package Contents

Pink, oval, biconvex tablets, with beveled edges, film-coated, with the engraving "40" on one face and smooth on the other.

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

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2.

28223 Pozuelo de Alarcón (Madrid)

Spain

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

Date of the Last Revision of this Prospectus: 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 Health Products (AEMPS) http://www.aemps.gob.es/

This information is intended only for healthcare professionals:

Administration through a 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, dispersion in 50 ml of water is required to prevent the pellets from clogging the tube.
2. Shake the syringe immediately for approximately 2 minutes to disperse the tablet.
3. Hold the syringe with the tip up and check that the tip is not clogged.
4. Connect the syringe to the tube while maintaining the previous position.

5. Shake the syringe and place it with the tip down. Inject immediately 5-10 ml into the tube. Invert the syringe after injection and shake (the syringe must be kept with the tip up to avoid clogging the tip).

1. Put the syringe back with the tip down and inject immediately another 5-10 ml into the tube. Repeat this procedure until the syringe is empty.
2. Fill the syringe with 25 ml of water and 5 ml of air and repeat step 5 if necessary to drag any sediment remaining in the syringe. For some tubes, 50 ml of water are necessary.