NAPROXEN/ESOMEPRAZOLE SANDOZ 500 mg/20 mg MODIFIED-RELEASE TABLETS

Introduction

Package Leaflet: Information for the User

Naproxen/Esomeprazol Sandoz 500 mg/20 mg Modified Release Tablets EFG

naproxen/esomeprazol

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What Naproxen/Esomeprazol Sandoz is and what it is used for
2. What you need to know before you take Naproxen/Esomeprazol Sandoz
3. How to take Naproxen/Esomeprazol Sandoz
4. Possible side effects
5. Storing Naproxen/Esomeprazol Sandoz
6. Contents of the pack and other information

1. What Naproxen/Esomeprazol Sandoz is and what it is used for

What Naproxen/Esomeprazol Sandoz is

Naproxen/Esomeprazol Sandoz contains two different medicines called naproxen and esomeprazol. Each of these medicines works in a different way.

• naproxen belongs to a group of medicines called “non-steroidal anti-inflammatory drugs” (NSAIDs). It reduces pain and inflammation,
• esomeprazol belongs to a group of medicines called “proton pump inhibitors”. It reduces the amount of acid in your stomach.

Esomeprazol helps to reduce the risk of ulcers and stomach problems that appear in patients who need to take NSAIDs.

What Naproxen/Esomeprazol Sandoz is used for

Naproxen/esomeprazol is used in adults for the relief of symptoms of:

• osteoarthritis,
• rheumatoid arthritis,
• ankylosing spondylitis.

Naproxen/esomeprazol helps to reduce pain, swelling, redness, and heat (inflammation).

You will receive this medicine if it is considered unlikely that a lower dose of NSAID will relieve your pain and you are at risk of developing a stomach ulcer or an ulcer in the first part of the small intestine (duodenum) while taking an NSAID.

2. What you need to know before you take Naproxen/Esomeprazol Sandoz

Do not take Naproxen/Esomeprazol Sandoz if:

• you are allergic (hypersensitive) to naproxen,
• you are allergic to esomeprazol or other proton pump inhibitors,
• you are allergic to any of the other ingredients of this medicine (listed in section 6),
• you are taking a medicine called “atazanavir” or “nelfinavir” (used to treat HIV infection),
• acetylsalicylic acid (e.g. aspirin), naproxen or other NSAIDs such as ibuprofen, diclofenac or COX-2 inhibitors (e.g. celecoxib, etoricoxib) have ever caused you asthma (wheezing), or an allergic reaction such as itching or skin rash (urticaria),
• you are in the last 3 months of pregnancy,
• you have severe liver, kidney, or heart problems,
• you have a stomach ulcer or intestinal ulcer,
• you have any bleeding disorder or severe or unexpected bleeding.

Do not take naproxen/esomeprazol if you are in any of the above situations. If you are not sure, consult your doctor or pharmacist before taking naproxen/esomeprazol.

Warnings and precautions

Consult your doctor or pharmacist before starting to take naproxen/esomeprazol.

Do not take naproxen/esomeprazol and consult your doctor immediately if you experience any of the following episodes before or during treatment with naproxen/esomeprazol, as this medicine may mask the symptoms of another illness:

• if you lose a lot of weight without reason and have trouble swallowing,
• if you vomit food or blood,
• if your stools are black (blood-stained).

If you are in any of these situations (or are unsure), consult your doctor or pharmacist before taking this medicine.

Consult your doctor or pharmacist before taking this medicine if:

• you have inflammation in your intestines (Crohn's disease or ulcerative colitis),
• you have other liver or kidney problems or if you are elderly,
• you are taking medicines such as oral corticosteroids, warfarin, clopidogrel, Selective Serotonin Reuptake Inhibitors (SSRIs), acetylsalicylic acid (aspirin) or NSAIDs including COX-2 inhibitors (see section “Other medicines and Naproxen/Esomeprazol Sandoz”),
• you have ever had a skin reaction after treatment with a medicine similar to esomeprazol (a component of Naproxen/Esomeprazol Sandoz) to reduce stomach acid,
• a specific blood test (Chromogranin A) is scheduled for you.

If you are in any of these situations (or are unsure), consult your doctor or pharmacist before taking this medicine.

If you have had a stomach ulcer or bleeding before, inform your doctor. You will be asked to inform your doctor of any unusual stomach symptoms (e.g. pain).

Some medicines like naproxen/esomeprazol may be associated with a small increased risk of heart attack (myocardial infarction) or stroke. The risk is always greater with higher doses and longer treatment. Do not exceed the recommended dose or duration of treatment.

Naproxen/esomeprazol contains the NSAID naproxen. Like all NSAIDs, naproxen should be used at the lowest effective dose with the shortest possible treatment duration to reduce the risk of unwanted effects. Your doctor will therefore assess at regular intervals whether naproxen/esomeprazol is still appropriate for you.

Naproxen/esomeprazol is not suitable for rapid relief of acute pain, as it takes several hours for the analgesic naproxen to reach the bloodstream.

Consult your doctor before taking this medicine if you have any heart problems, a history of stroke, or think you are at risk of these problems. You may be at risk of these problems if:

• you have high blood pressure,
• you have circulation or coagulation problems,
• you are diabetic,
• you have high cholesterol levels,
• you are a smoker.

Taking a proton pump inhibitor (which is one of the components of Naproxen/Esomeprazol Sandoz), especially for more than a year, may slightly increase the risk of hip, wrist, or spine fractures. Inform your doctor if you have osteoporosis or if you are taking corticosteroids (which may increase the risk of osteoporosis).

If you experience a skin rash, especially in areas of the skin exposed to the sun, consult your doctor as soon as possible, as it may be necessary to interrupt treatment with naproxen/esomeprazol. Remember to mention any other symptoms you may notice, such as joint pain.

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

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

There have been reports of severe skin reactions, including Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (Lyell's syndrome), and drug reaction with eosinophilia and systemic symptoms (DRESS), in association with naproxen/esomeprazol. Stop taking naproxen/esomeprazol and consult your doctor immediately if you observe any of the symptoms related to severe skin reactions described in section 4.

During treatment with naproxen/esomeprazol, kidney inflammation may occur. The signs and symptoms may include decreased urine volume or blood in the urine and/or hypersensitivity reactions such as fever, skin rash, and joint stiffness. You should inform your doctor of these signs.

Children and adolescents

Naproxen/esomeprazol is not recommended for use in children or adolescents under 18 years of age.

Other medicines and Naproxen/Esomeprazol Sandoz

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription, including herbal medicines. This is because naproxen/esomeprazol may affect the way other medicines work. There are also some medicines that may affect the way naproxen/esomeprazol works.

Do not take this medicine and inform your doctor or pharmacist if you are taking:

• a medicine called “atazanavir” or “nelfinavir” (used to treat HIV infection).

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

• acetylsalicylic acid (aspirin) (used as a pain reliever or to prevent blood clots). If you are taking low doses of acetylsalicylic acid (aspirin), you may still be able to take naproxen/esomeprazol,
• other NSAIDs (including COX-2 inhibitors),
• certain medicines such as ketoconazole, itraconazole, posaconazole, or voriconazole (used to treat fungal infections),
• erlotinib (or another anticancer medicine of the same class),
• cholestyramine (used to reduce cholesterol),
• clarithromycin (used to treat infections),
• “quinolone antibiotics” (for infections), such as ciprofloxacin or moxifloxacin,
• diazepam (used to treat anxiety, relax muscles, or in epilepsy),
• hydantoins such as phenytoin (used to treat epilepsy),
• lithium (used to treat certain types of depression),
• methotrexate (used to treat rheumatoid arthritis, psoriasis, and cancer),
• probenecid (used for gout),
• “Selective Serotonin Reuptake Inhibitors” (SSRIs) (used to treat severe depression and anxiety disorders),
• cyclosporin or tacrolimus (medicines used to reduce the body's immune reactions),
• digoxin (used to treat heart problems),
• sulfonylureas such as glimepiride (oral medicines used to control blood sugar levels in diabetes),
• medicines used to treat high blood pressure that are called diuretics (such as furosemide or hydrochlorothiazide), ACE inhibitors (such as enalapril), angiotensin II receptor antagonists (such as losartan), and beta-blockers (such as propranolol),
• corticosteroid medicines such as hydrocortisone or prednisolone (used as anti-inflammatory medicines),
• medicines to prevent blood clotting, such as warfarin, dicumarol, heparin, or clopidogrel,
• rifampicin (used to treat tuberculosis),
• St. John's Wort (Hypericum perforatum) (used to treat mild depression),
• cilostazol (used for leg pain due to poor blood flow).

If you are in any of these situations (or are unsure), consult your doctor or pharmacist before taking naproxen/esomeprazol.

Taking Naproxen/Esomeprazol Sandoz with food and drinks

Do not take naproxen/esomeprazol with food, as it may reduce and/or delay the effect of this medicine. Take the tablets at least 30 minutes before meals.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

• do not take naproxen/esomeprazol if you are in the last 3 months of pregnancy, as it may harm the fetus or cause problems during delivery. It may cause kidney and heart problems in the fetus. It may affect bleeding tendency, yours and your baby's, and that delivery may be delayed or prolonged more than expected. You should not use naproxen/esomeprazol during the first 6 months of pregnancy unless it is absolutely necessary and your doctor advises you to do so. If you need treatment during this period or while trying to become pregnant, you should use the lowest dose for the shortest possible time. If you take it for more than a few days from the 20th week of pregnancy, naproxen/esomeprazol may cause kidney problems in the fetus that can lead to low levels of the fluid surrounding the baby (oligohydramnios) or narrowing of a blood vessel (ductus arteriosus) in the baby's heart. If you need to prolong treatment for more than a few days, your doctor may recommend additional monitoring.

Breastfeeding

• do not breastfeed if you are taking naproxen/esomeprazol, as small amounts may pass into breast milk. If you are planning to breastfeed, do not take this medicine.

Fertility

• naproxen/esomeprazol may make it difficult for you to become pregnant. You should inform your doctor if you are planning a pregnancy or are having difficulty becoming pregnant.

Driving and using machines

You may feel dizzy or experience blurred vision during treatment with naproxen/esomeprazol. If this happens, do not drive or use tools or machines.

Naproxen/Esomeprazol Sandoz contains lactose

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

This medicine contains less than 1 mmol of sodium (23 mg) per modified release tablet; this is essentially “sodium-free”.

3. How to take Naproxen/Esomeprazol Sandoz

Follow the instructions for administration of this medicine exactly as indicated by your doctor. If you are unsure, consult your doctor or pharmacist again.

How to take this medicine

• swallow the tablets whole with water. Do not break, chew, or crush the tablets. It is important that you swallow the tablets whole for the medicine to work correctly,
• take the tablets at least 30 minutes before meals. Food may reduce the protective effect of this medicine on your stomach and intestines. Food may also cause a significant delay in the relief of pain and inflammation,

How much to take

• take one tablet twice a day for the time indicated by your doctor,
• naproxen/esomeprazol is only available as 500 mg/20 mg. If your doctor thinks this dose is not suitable for you, they may prescribe another treatment.

If you take more Naproxen/Esomeprazol Sandoz than you should

If you take more naproxen/esomeprazol than you should, consult your doctor or pharmacist immediately. The symptoms of an overdose may include lethargy, dizziness, drowsiness, abdominal pain and/or discomfort, heartburn, indigestion, nausea, liver problems (which can be seen in a blood test), kidney problems that can be severe, high levels of acid in your blood, disorientation, vomiting, stomach or intestinal bleeding, high blood pressure, breathing difficulties, coma, sudden allergic reactions (which can include shortness of breath, skin rashes, swelling of the face and/or throat, and/or collapse), and uncontrolled body movements.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount taken.

If you forget to take Naproxen/Esomeprazol Sandoz

• do not take a double dose (two doses at the same time) to make up for missed 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. The following adverse effects may occur with this medicine.

Stop taking naproxen/esomeprazol and consult a doctor immediately if you notice any of the following serious adverse effects - you may need urgent medical treatment:

• sudden ringing, swelling of the lips, tongue, and throat or body, skin rash, fainting, or difficulty swallowing (severe allergic reaction),
• sudden appearance of a severe rash or skin redness with blistering or peeling, even after several weeks of treatment. Severe blisters and bleeding in the lips, eyes, mouth, nose, and genitals may also occur. Skin rashes can become severe and widespread skin damage (exfoliation of the epidermis and superficial mucous membranes) with potentially fatal consequences. This could be a "multiform erythema", "Stevens-Johnson syndrome", "toxic epidermal necrolysis", or "drug reaction with eosinophilia and systemic symptoms". These effects are very rare and may affect up to 1 in 10,000 people,
• yellowing of the skin or whites of the eyes, dark urine, and fatigue, which can be symptoms of liver problems,
• medicines like naproxen/esomeprazol may be associated with a small increased risk of having a heart attack (myocardial infarction) or stroke. The signs are chest pain that radiates to the neck and shoulders and down the left arm, confusion, or numbness or muscle weakness that can affect only one side of the body,
• dark, sticky stools or bloody diarrhea,
• vomiting blood or dark particles that resemble coffee grounds.

Tell your doctor as soon as possible if you experience any of the following symptoms:

In rare cases, naproxen/esomeprazol can affect the white blood cells in the blood, leading to immunosuppression.

If you have an infection with symptoms such as fever with a severe worsening of your general health or fever with symptoms of local infection such as neck, throat, or mouth pain or difficulty urinating, you should consult your doctor as soon as possible to rule out a lack of white blood cells (agranulocytosis) through a blood test. It is essential that you inform your doctor about your medication at that time.

Other adverse effects are:

Frequent (may affect up to 1 in 10 people)

• headache,
• feeling of fatigue,
• feeling of thirst,
• feeling of depression,
• shortness of breath,
• increased sweating,
• skin itching and rash,
• feeling of dizziness (vertigo),
• red or purple spots, bruises, or patches on the skin,
• feeling sick (nausea) or being sick (vomiting),
• heart palpitations,
• sleep disturbances or insomnia,
• hearing problems or ringing in the ears,
• dizziness, feeling of drowsiness, or feeling of fainting,
• swelling of the hands, feet, and ankles (edema),
• mouth inflammation,
• vision problems,
• diarrhea, stomach pain, acidity, indigestion, constipation, belching, or gas (flatulence).
• stomach ulcers or ulcers in the first part (duodenum) of the small intestine.
• gastritis (inflammation of the stomach lining),
• benign stomach polyps.

Uncommon, rare, or very rare (may affect up to 1 in 100 people or less)

• mouth sores or ulcers,
• vision problems such as blurred vision, conjunctivitis, or eye pain,
• strange dreams,
• sleepiness,
• increased blood sugar levels. Symptoms may include thirst and increased urination,
• low blood sugar levels. Symptoms may include hunger or weakness, sweating, and an increased heart rate,
• coma,
• blood vessel inflammation,
• perforation (hole) in the stomach or intestine,
• systemic lupus erythematosus (SLE), a disease in which the immune system attacks the body, causing joint pain, skin rashes, and fever,
• lymph node enlargement,
• hip, wrist, or spine fracture (if naproxen/esomeprazol is used in high doses and for extended periods),
• fever,
• fainting,
• dry mouth,
• aggression,
• hearing loss,
• asthma attacks,
• tremors or convulsions,
• menstrual problems,
• weight changes,
• hair loss (alopecia),
• skin rash with blisters,
• joint pain (arthralgia),
• breast enlargement in males,
• tongue pain or swelling,
• muscle spasms or tremors,
• appetite or taste disturbances,
• muscle weakness (myalgia),
• blood may take longer to clot,
• difficulty becoming pregnant if you are a woman,
• fever, redness, or other signs of infection,
• irregular, slow, or very fast heartbeats,
• tingling sensation,
• memory or concentration difficulties,
• feeling of agitation, confusion, anxiety, or nervousness,
• general feeling of discomfort, weakness, and lack of energy,
• edema or pain in some parts of the body due to fluid retention,
• high or low blood pressure. You may experience dizziness or fainting,
• skin rash or blistering, or increased skin sensitivity to sunlight,
• seeing, feeling, or hearing things that do not exist (hallucinations),
• changes in blood test results, such as those used to check liver function. Your doctor can explain this better,
• a fungal infection called "candidiasis" that can affect the intestine,
• blood in the urine or other kidney problems. You may have back pain,
• difficulty breathing, which can worsen slowly. It may indicate the development of pneumonia or lung inflammation,
• low sodium levels in the blood, which can cause weakness, vomiting, and cramps.
• meningitis symptoms such as fever, feeling of discomfort, neck stiffness, headache, sensitivity to bright light, and confusion,
• pancreas problems. The signs include severe stomach pain that radiates to the back,
• light-colored stools, which are a sign of severe liver problems (hepatitis). Severe liver problems that cause liver failure and brain damage,
• colitis or worsening of inflammatory bowel disease, such as Crohn's disease or ulcerative colitis. The signs include stomach pain, diarrhea, vomiting, and weight loss.
• blood problems, such as a decrease in red blood cells (anemia), white blood cells, or platelets, which can cause weakness, bruising, fever, chills, sore throat, or more frequent infections,
• an increase in the number of a certain type of white blood cell (eosinophilia),
• a lack of all types of blood cells (pancytopenia),
• problems with the way the heart pumps blood to the body or damage to blood vessels. The symptoms are fatigue, difficulty breathing, weakness, chest pain, or generalized pain.

Frequency not known (cannot be estimated from available data)

• skin rash, possibly with joint pain,
• widespread skin rash, elevated body temperature, high liver enzyme levels, blood abnormalities (eosinophilia), lymph node enlargement, and involvement of other body organs (Drug Reaction with Eosinophilia and Systemic Symptoms, also known as DRESS). See also section 2,
• a characteristic skin allergic reaction known as fixed drug eruption, which usually reappears in the same location when re-exposed to the medicine and can be seen as red, round, or oval patches and skin swelling, blisters (urticaria), and itching.

Do not worry about this list of possible adverse effects.You may not experience any of them.

Reporting adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the Spanish Medicines Agency's website: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Naproxen/Esomeprazol Sandoz

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

Do not use this medicine after the expiration date stated on the packaging or bottle after CAD/EXP. The expiration date is the last day of the month indicated.

Store below 25°C.

Keep this medicine in its original packaging to protect it from light.

Keep the bottle tightly closed to protect it from moisture.

After opening the bottle for the first time: use within 60 days.

Medicines should not be disposed of via wastewater or household waste. Deposit the packaging and any unused medicines in the pharmacy's SIGRE collection point. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Naproxen/Esomeprazol Sandoz

• The active ingredients are naproxen and esomeprazol.
• Each modified-release tablet contains 500 mg of naproxen and 20 mg of esomeprazol (as magnesium trihydrate).
• The other ingredients (excipients) of the tablet core are anhydrous colloidal silica, methacrylic acid-ethyl acrylate copolymer (1:1) dispersion 30%, polysorbate 80, glycerol monostearate 40-55, triethyl citrate, lactose monohydrate, sodium croscarmellose, sodium stearyl fumarate, microcrystalline cellulose type 112, microcrystalline cellulose type 302, magnesium oxide, povidone K30, calcium stearate, and in the coating material hypromellose, macrogol 400, titanium dioxide, and yellow iron oxide.

Appearance and Package Contents

Modified-release tablets are oblong, biconvex (8.9 mm x 19.4 mm), and coated with a yellow film on both sides.

The modified-release tablets are packaged in HDPE bottles containing silica gel desiccant (to keep the tablets dry) closed with an aluminum induction seal and a screw cap. The desiccant in the bottle is not suitable for consumption.

Package sizes: 30 and 60 modified-release tablets.

Not all package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Sandoz Farmacéutica, S.A.

Centro Empresarial Parque Norte

Edificio Roble

C/ Serrano Galvache, 56

28033 Madrid

Spain

Manufacturer

Salutas Pharma GmBH

Otto-von-Guericke-Allee 1

39179 Barleben

Germany

Flavine Pharma France

3 Voie d’Allemagne,

Vitrolles, 13127

France

Interpharma Services Ltd.

11, Rusalijski prohod Str., fl. 3, ap. 8,

Sofia 1407

Bulgaria

Date of the last revision of the leaflet:09/2024

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/