Esonalgen

Patient Information Leaflet

, 500 mg + 20 mg, modified-release tablets
Naproxen + Esomeprazole
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm others, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of Contents

1. What ESONALGEN is and what it is used for
2. What you need to know before taking ESONALGEN
3. How to take ESONALGEN
4. Possible side effects
5. How to store ESONALGEN
6. Contents of the pack and other information

1. What ESONALGEN is and what it is used for

What ESONALGEN is
ESONALGEN contains two different active substances: naproxen and esomeprazole. 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.
• Esomeprazole belongs to a group of medicines called "proton pump inhibitors". It reduces the production of hydrochloric acid in the stomach.

Esomeprazole helps reduce the risk of stomach ulcers and other gastric problems that may occur in patients who require long-term treatment with NSAIDs.

What ESONALGEN is used for
ESONALGEN is used in adults to relieve symptoms of the following conditions:

• Osteoarthritis
• Rheumatoid arthritis
• Ankylosing spondylitis

ESONALGEN helps reduce pain, swelling, redness, and increased temperature (inflammation).
You will be prescribed this medicine if low doses of NSAIDs alone are ineffective in controlling pain and you are at risk of developing a stomach ulcer or duodenal ulcer while taking NSAIDs.

2. Important information before using ESONALGEN

When not to use ESONALGEN:

• If the patient is allergic (hypersensitive) to naproxen.
• If the patient is allergic to esomeprazole or other proton pump inhibitors.
• If the patient is allergic to any of the other ingredients of this medicine (listed in section 6).
• If the patient is concurrently taking atazanavir or nelfinavir (used in the treatment of HIV infection).
• If, after taking acetylsalicylic acid (e.g. aspirin), naproxen or other NSAIDs such as ibuprofen, diclofenac or COX-2 inhibitors (e.g. celecoxib, etoricoxib), the patient has experienced asthma (wheezing) or an allergic reaction such as skin itching or skin rash (urticaria).
• If the patient is in the last 3 months of pregnancy.
• If the patient has severe problems with the liver, kidneys or heart.
• If the patient has peptic ulcers of the stomach or intestines.
• If the patient has bleeding disorders or severe and unexpected bleeding.

If any of the above situations apply, do not take ESONALGEN. If you are unsure, consult your doctor or pharmacist before taking ESONALGEN.

Warnings and precautions

Before starting treatment with ESONALGEN, discuss this with your doctor or pharmacist.

Do not take ESONALGEN and contact your doctor immediately if any of the following conditions occurred previously or during treatment with ESONALGEN, as this medicine may mask symptoms of another disease:

• Significant, unintentional weight loss and difficulty swallowing.
• Vomiting or vomiting with blood.
• Tarry stools (stool coloured by blood). If any of these conditions apply to the patient (or if the patient has any doubts), consult your doctor or pharmacist before taking this medicine.

Before taking this medicine, consult your doctor or pharmacist if:

• The patient has inflammatory bowel disease (Crohn's disease or ulcerative colitis).
• The patient has any other liver or kidney diseases or is elderly.
• The patient is taking medicines such as oral corticosteroids, warfarin, clopidogrel, selective serotonin reuptake inhibitors (SSRIs), acetylsalicylic acid or NSAIDs, including COX-2 inhibitors (see section ESONALGEN and other medicines).
• The patient has ever had a skin reaction after taking a medicine similar to esomeprazole (a component of ESONALGEN) that reduces gastric acid secretion.
• If the patient needs to undergo a specific blood test (chromogranin A measurement).

If any of the above situations apply to the patient (or if the patient has any doubts), inform your doctor or pharmacist before taking this medicine.

If the patient has previously had stomach ulcers or bleeding, inform the doctor. The patient will be asked to report any unusual stomach symptoms (e.g. pain) to the doctor.

Medicines such as ESONALGEN may be associated with a small increased risk of heart attack (myocardial infarction) or stroke. The risk increases with higher doses and long-term treatment. Do not exceed the recommended dose or duration of treatment.

ESONALGEN contains naproxen, an NSAID. As with all NSAIDs, naproxen should be used at the lowest effective dose for the shortest possible time to reduce the risk of adverse effects. Your doctor will therefore regularly assess whether ESONALGEN remains appropriate for the patient.

ESONALGEN is not suitable for rapid relief of acute pain, as it takes several hours for the pain-relieving substance naproxen to be absorbed into the blood.

Before taking the medicine, also inform your doctor if the patient has heart problems, has previously had a stroke, or believes they are at risk of these conditions.

The patient may be at risk of these conditions if:

• The patient has high blood pressure.
• The patient has problems with blood circulation or blood clotting.
• The patient has diabetes.
• The patient has high blood cholesterol levels.
• The patient smokes.

The use of a proton pump inhibitor (a component of ESONALGEN), particularly for longer than one year, may slightly increase the risk of fractures of the hip, wrist or spine. Inform your doctor if the patient has osteoporosis or is taking corticosteroids (medicines that may increase the risk of developing osteoporosis).

If a skin rash appears, especially in areas exposed to sunlight, inform your doctor as soon as possible, as treatment with ESONALGEN may need to be discontinued. Remember to mention any other symptoms, such as joint pain.

Serious skin rashes have occurred in patients taking esomeprazole (see also section 4). The rash may involve ulceration of the mouth, throat, nose, genital organs and conjunctiva (red, swollen eyes). These serious skin rashes often occur after flu-like symptoms such as fever, headache and body aches. The rash may cover large areas of the body, with blisters and skin peeling.

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

Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported with the use of ESONALGEN. Discontinue ESONALGEN and seek immediate medical help if any of the symptoms associated with these serious skin reactions described in section 4 occur.

During treatment with ESONALGEN, inflammation of the kidneys may occur. Symptoms may include: reduced urine volume or blood in the urine and/or hypersensitivity reactions such as fever, rash and joint stiffness. Inform your doctor if such symptoms occur.

Children and adolescents

ESONALGEN is not recommended for use in children and adolescents under 18 years of age.

ESONALGEN and other medicines

Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken or plans to take, including over-the-counter medicines and herbal remedies. This is important because ESONALGEN may affect the action of other medicines, and the effect of ESONALGEN may also be altered by other medicines.

Do not take this medicine and inform your doctor or pharmacist if the patient is taking:

• A medicine called "atazanavir" or "nelfinavir" (used in the treatment of HIV infection).

Inform your doctor or pharmacist if the patient is taking any of the following medicines:

• Acetylsalicylic acid (used as a painkiller or to prevent blood clots). If the patient is taking low-dose acetylsalicylic acid, they may continue taking ESONALGEN.
• Other NSAIDs (including COX-2 inhibitors).
• Certain medicines such as ketoconazole, itraconazole, posaconazole or voriconazole (used to treat fungal infections).
• Erlotinib (or another anticancer drug from the same class).
• Cholestyramine (a medicine used to lower blood cholesterol levels).
• Clarithromycin (a medicine used to treat infections).
• "Quinolone antibiotics" (used for infections), such as ciprofloxacin or moxifloxacin.
• Diazepam (a medicine used to treat anxiety, to relax muscles or to treat epilepsy).
• Hydantoin derivatives such as phenytoin (a medicine used to treat epilepsy).
• Lithium salts (a medicine used to treat certain types of depression).
• Methotrexate (a medicine used to treat rheumatoid arthritis, psoriasis and cancer).
• Probenecid (a medicine used to treat gout).
• "Selective serotonin reuptake inhibitors" (SSRIs) (medicines used to treat major depression and anxiety).
• Cyclosporine or tacrolimus (medicines used to suppress the body's immune response).
• Digoxin (used for heart rhythm disorders).
• Sulfonylurea derivatives such as glimepiride (oral medicines used to control blood sugar levels in diabetes).
• Medicines used to treat high blood pressure called diuretics (such as furosemide or hydrochlorothiazide), ACE inhibitors (such as enalapril), angiotensin II receptor antagonists (e.g. losartan) and beta-blockers (such as propranolol).
• Corticosteroids such as hydrocortisone or prednisolone (used for anti-inflammatory purposes).
• Anticoagulants such as warfarin, dicoumarol, heparin or clopidogrel.
• Rifampicin (used to treat tuberculosis).
• St. John's wort (Hypericum perforatum) (used to treat mild depression).
• Cilostazol (a medicine used for leg pain caused by poor blood flow).

If any of the above situations apply to the patient (or if the patient has any doubts), inform your doctor or pharmacist before taking ESONALGEN.

ESONALGEN with food and drink

Do not take ESONALGEN with food, as this may reduce and/or delay the effect of ESONALGEN. Tablets should be taken at least 30 minutes before a meal.

Pregnancy, breastfeeding and fertility

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a baby, she should consult her doctor or pharmacist before taking this medicine.

Pregnancy

Do not take ESONALGEN during the last 3 months of pregnancy, as it may harm the unborn child or cause complications during delivery. It may cause kidney and heart problems in the unborn child. It may affect bleeding tendency in both the patient and her child and may cause delivery to be delayed or prolonged. Do not use the medicine during the first 6 months of pregnancy unless absolutely necessary and recommended by a doctor. If treatment is required during this period or when trying to conceive, use the lowest dose for the shortest possible time. If the medicine is taken for more than a few days starting from week 20 of pregnancy, it may cause kidney problems in the unborn child, which may lead to low amniotic fluid volume (oligohydramnios) or narrowing of a blood vessel (ductus arteriosus) in the child's heart. If treatment is required for longer than a few days, your doctor may recommend additional monitoring.

Breastfeeding

Do not breastfeed while taking ESONALGEN. This is because small amounts of the medicine may pass into breast milk. If the patient plans to breastfeed, she should not take ESONALGEN.

Fertility

The medicine ESONALGEN may make it more difficult to become pregnant. Inform your doctor if the patient is planning pregnancy or has difficulty becoming pregnant.

Driving and using machines

Dizziness or visual disturbances may occur while taking ESONALGEN. If these occur, do not drive, operate tools or machinery.

ESONALGEN contains lactose

If the patient has previously been diagnosed with an intolerance to certain sugars, the patient should consult their doctor before taking the medicine.

The medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. the medicine is considered "sodium-free".

3. How to use ESONALGEN

ESONALGEN should always be used as directed by the physician. In case of doubts, consult a doctor or pharmacist.

How to take the medicine

• The tablets should be swallowed whole with water. Do not chew, divide or crush the tablets. It is important to take the tablets whole so that the medicine works properly.

• Tablets should be taken at least 30 minutes before a meal. Food may reduce the protective effect of ESONALGEN on the stomach and intestines. Food may also cause a significant delay in pain relief and reduction of inflammation.

• If a patient uses this medicine for a prolonged period, the doctor may decide to monitor the patient (especially if the patient has been using the medicine for longer than one year).

Dosage

• Take one tablet twice daily for the duration specified by the physician.
• ESONALGEN is available only in the dose of 500 mg + 20 mg. If the physician determines that this dosage is not appropriate for the patient, alternative treatment may be recommended.

Overdose of ESONALGEN
In case of taking more than the recommended dose of ESONALGEN, seek immediate advice from a doctor or pharmacist. Possible symptoms of overdose include: lethargy, dizziness, drowsiness, pain and/or discomfort in the upper abdomen, heartburn, indigestion, nausea, liver function disorders (shown in blood tests), kidney function disorders which may be serious, increased blood acid levels, confusion, vomiting, gastrointestinal bleeding, high blood pressure, breathing difficulties, coma, sudden allergic reactions (which may include shortness of breath, skin rash, swelling of the face and/or throat, and/or collapse), and uncontrolled body movements.

Missed dose of ESONALGEN

• A missed dose should be taken as soon as possible. However, if it is almost time for the next dose, do not take the missed dose.
• Do not take a double dose (two doses at the same time) to make up for a missed dose.

If you have any further doubts regarding the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
The following adverse effects may occur after using this medicine.
You must stop taking Esonalgen and contact your doctor immediately if any of the following severe adverse effects occur – prompt treatment may be necessary:

• Sudden onset of wheezing, swelling of the lips, tongue or throat, rash, fainting or difficulty swallowing (severe allergic reaction).
• Sudden onset of severe skin rash or redness with blisters or peeling may occur even several weeks after starting treatment. Blisters and bleeding of the lips, eyes, mouth, nose or genitals may also occur. Skin rashes may progress to serious, widespread skin damage (peeling of the epidermis and superficial mucous membranes) with potentially life-threatening consequences. This may be "erythema multiforme", "Stevens-Johnson syndrome", "toxic epidermal necrolysis" or "drug reaction with eosinophilia and systemic symptoms". These reactions 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 may be signs of liver dysfunction.
• Use of medicines such as Esonalgen may be associated with a small increased risk of heart attack (myocardial infarction) or stroke. Symptoms include chest pain radiating to the neck and arms, particularly along the left arm, confusion, muscle weakness or stiffness affecting only one side of the body.
• Passing black, sticky stools or bloody diarrhoea.
• Vomiting blood or black, coffee-ground-like material.

Contact your doctor immediately if any of the following symptoms occur:
In rare cases, Esonalgen may affect the function of white blood cells, leading to weakened immunity.
If the patient develops an infection with symptoms such as fever with a very poor general condition, or fever with local signs of infection such as neck, throat or mouth pain, or difficulty urinating, medical advice should be sought as soon as possible to allow blood tests to rule out a lack of white blood cells (agranulocytosis). It is important to inform the doctor about the medicine being taken.
Other adverse effects include:
Common (may affect up to 1 in 10 people)

• Headache.
• Feeling tired.
• Feeling thirsty.
• Feeling depressed.
• Shortness of breath.
• Excessive sweating.
• Itchy skin and skin rashes.
• Sensation of spinning (vertigo of labyrinthine origin).
• Red or purple spots, bruises or marks on the skin.
• Nausea or vomiting.
• Palpitations (awareness of heart beating).
• Sleep disturbances or difficulty falling asleep (insomnia).
• Hearing disturbances or ringing in the ears (tinnitus).
• Dizziness, drowsiness or feeling unbalanced.
• Swelling of hands, feet and ankles (oedema).
• Inflammation of the mouth.
• Vision disturbances.
• Diarrhoea, stomach pain, heartburn, indigestion, constipation, belching or bloating with flatulence.
• Stomach ulcer or duodenal ulcer (in the first part of the small intestine).
• Inflammation of the stomach lining (gastritis).
• Benign gastric polyps.

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

• Mouth pain or mouth ulceration.
• Vision disturbances such as blurred vision, conjunctivitis or eye pain.
• Strange dreams.
• Drowsiness.
• Increased blood glucose (sugar) levels. Possible symptoms include feeling thirsty and increased urination.
• Low blood glucose (sugar) levels. Possible symptoms include feeling hungry or weak, sweating and rapid heartbeat.
• Coma.
• Vasculitis (inflammation of blood vessels).
• Perforation (punching a hole) of 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.
• Swollen lymph nodes.
• Fractures of the hip, wrist or spine (in cases of long-term, high-dose use of Esonalgen).
• Fever.
• Fainting.
• Dry mouth.
• Aggression.
• Hearing loss.
• Asthma attack.
• Seizures.
• Menstrual disorders.
• Changes in body weight.
• Hair loss (alopecia).
• Raised, itchy rash (urticaria).
• Joint pain (arthralgia).
• Breast enlargement in men.
• Tongue pain or swelling.
• Small muscle cramps or tremors.
• Changes in appetite or taste disturbances.
• Muscle weakness or muscle pain (myalgia).
• Prolonged blood clotting time.
• In women, difficulty becoming pregnant.
• Fever, redness or other signs of infection.
• Irregular, slow or very rapid heartbeat.
• Tingling and numbness.
• Memory or concentration difficulties.
• Feeling agitated, confused, anxious or restless.
• General malaise, weakness and lack of energy.
• Swelling or pain in body parts due to fluid retention.
• High or low blood pressure. May cause fainting or dizziness.
• Skin rash, blistering or increased sensitivity to sunlight.
• Seeing, feeling or hearing things that are not real (hallucinations).
• Changes in blood test results indicating liver function. Your doctor will explain this in detail.
• Fungal infection called "candidiasis", which may affect the intestines.
• Blood in urine or other kidney function disturbances. May be accompanied by back pain.
• Breathing difficulties, which may gradually worsen. These may be symptoms of developing lung inflammation or pulmonary oedema.
• Low blood sodium levels. May cause weakness, vomiting and cramps.
• Symptoms of meningitis such as fever, nausea, vomiting, stiff neck, headache, light sensitivity and confusion.
• Pancreatic dysfunction. Symptoms include severe abdominal pain radiating to the back.
• Pale stools, which may indicate severe liver disease (hepatitis). Severe liver disease may lead to liver failure and brain function disturbances.
• Inflammation of the large intestine or worsening of inflammatory bowel disease such as Crohn's disease or ulcerative colitis. Symptoms include abdominal pain, diarrhoea, vomiting and weight loss.
• Blood disorders such as reduced number of red blood cells (anaemia), white blood cells or platelets. This may cause weakness, bruising, fever, severe chills, sore throat or increased susceptibility to infections.
• Increased number of certain types of white blood cells (eosinophilia).
• Deficiency of all types of blood cells (pancytopenia).
• Problems with the way the heart pumps blood through the body or damage to blood vessels. Symptoms may include fatigue, shortness of breath, weakness, chest pain or generalized pain.

Frequency unknown (cannot be estimated from available data)

• If the patient takes Esonalgen for longer than three months, blood magnesium levels may decrease. Low magnesium levels may cause fatigue, involuntary muscle spasms, disorientation, seizures, dizziness or rapid heartbeat. If any of these symptoms occur, the doctor should be informed immediately. Low magnesium levels may also lead to reduced potassium or calcium levels in the blood. The doctor may recommend periodic blood tests to monitor magnesium levels.
• Skin rash, possibly with joint pain.
• Widespread rash, high fever, elevated liver enzymes, blood abnormalities (eosinophilia), swollen lymph nodes and involvement of other organs (drug reaction with eosinophilia and systemic symptoms, also known as DRESS syndrome). See also section 2.
• A characteristic skin allergic reaction called fixed drug eruption, which typically recurs in the same location(s) upon re-exposure to the drug and may appear as round or oval red patches and swelling of the skin, blisters (urticaria) and itching.

Do not be alarmed by the possible adverse effects listed above. The patient may not experience any of them.
Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw,
tel.: +48 22 49 21 301, fax: +48 22 49 21 309,
website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps to provide more information on the safety of this medicine.

5. How to store ESONALGEN

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton or bottle after:
"EXP". The expiry date refers to the last day of the stated month.
Store below 25°C.
Keep in the original packaging to protect from light. Keep the bottle tightly closed to protect from moisture.
Shelf life after first opening the bottle: 60 days.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Esonalgen contains

• The active substances are naproxen and esomeprazole.
• Each modified-release tablet contains 500 mg of naproxen and 20 mg of esomeprazole (as esomeprazole magnesium trihydrate).
• The other ingredients (excipients) are: in the tablet core: colloidal anhydrous silica, copolymer of methacrylic acid and ethyl acrylate (1:1) (30% dispersion), 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; in the coating: hypromellose, macrogol 400, titanium dioxide, yellow iron oxide.

What Esonalgen looks like and contents of the pack
These are yellow, elongated, biconvex modified-release tablets, measuring 8.9 mm x 19.4 mm, coated yellow and smooth on both sides.
The coated tablets are packed in HDPE bottles containing a desiccant (to ensure tablet dryness), sealed with an induction aluminum seal and a screw cap. Do not ingest containers containing the desiccant.
Pack sizes – 30 or 60 modified-release tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50C
02-672 Warsaw
Poland
Tel: 22 209 70 00

Importer
Interpharma Services Ltd.
43A Cherni Vrach Blvd. Sofia 1407
Bulgaria
Flavine Pharma France
3 Voie d’Allemagne, Vitrolles, 13127
France
Salutas Pharma GmbH
Otto-von-Guericke Allee 1
39179 Barleben
Germany

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Estonia ESMAPREN
Lithuania Esmapren 500 mg/20 mg modifikuoto atpalaidavimo tabletės
Latvia Esmapren 500 mg/20 mg modificētās darbības tabletes
Austria Naproxen/Esomeprazol Sandoz 500 mg/20 mg Tabletten mit veränderter Wirkstofffreisetzung
Ireland Naproxen / Esomeprazole Rowex 500 mg/20 mg modified-release tablets
Spain Naproxeno/Esomeprazol Sandoz 500 mg/20 mg comprimidos de liberación modificada EFG
Finland Vamtexar 500 mg/20 mg säädellysti vapauttavat tabletit
Croatia Vamtexar 500 mg/20 mg tablete s prilagođenim oslobađanjem
Norway Vamtexar
Poland
Portugal Naproxeno + Esomeprazol Sandoz
Slovenia Combolly 500 mg/20 mg tablete s prirejenim sproščanjem
{logo of the marketing authorisation holder}