FEBUXOSTAT PHARMA COMBIX 80 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Febuxostat Pharma Combix 80 mg film-coated tablets EFG

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 is Febuxostat Pharma Combix and what is it used for
2. What you need to know before you take Febuxostat Pharma Combix
3. How to take Febuxostat Pharma Combix
4. Possible side effects
5. Storing Febuxostat Pharma Combix
6. Contents of the pack and other information

1. What is Febuxostat Pharma Combix and what is it used for

Febuxostat Pharma Combix contains the active substance febuxostat and is used to treat gout, which is associated with an excess in the body of a chemical compound called uric acid (urate). In some people, uric acid builds up in the blood to the point where it cannot be dissolved. When this happens, urate crystals form both inside and around the joints and kidneys. These crystals can cause sudden and intense pain, redness, heat, and swelling in the joints (called a gout attack). If left untreated, large deposits called tophi can form around the joints and inside them. Tophi can damage the joints and bones.

Febuxostat works by reducing the concentration of uric acid. Keeping uric acid levels low by taking febuxostat once a day prevents the formation of crystals and, over time, reduces symptoms. If uric acid levels are kept low for a long enough time, the size of tophi is also reduced.

Febuxostat is for adults.

2. What you need to know before you take Febuxostat Pharma Combix

Do not take Febuxostat:

• if you are allergic to febuxostat or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Consult your doctor or pharmacist before starting to take febuxostat:

• if you have or have had heart failure, other heart problems, or stroke
• if you have or have had kidney disease and/or severe allergic reactions to allopurinol (a medicine used to treat gout)
• if you have or have had liver disease or liver function disorders
• if you are being treated for high uric acid levels due to Lesch-Nyhan syndrome (a rare inherited disease in which there is too much uric acid in the blood)
• if you have thyroid problems.

If you experience allergic reactions to febuxostat, stop taking this medicine (see also section 4).

Possible symptoms of allergic reactions could be:

• rash including severe forms (e.g. blisters, nodules, exfoliative rash that itches), itching
• swelling of the limbs or face
• difficulty breathing
• fever with enlarged lymph nodes
• also severe allergic reactions that can put your life at risk, associated with cardiac arrest.

Your doctor may decide to permanently discontinue treatment with febuxostat.

Rare cases of life-threatening skin rashes (Stevens-Johnson syndrome) have been reported with the use of febuxostat, initially appearing on the trunk as red, target-like spots or circular patches that often have a blister in the center. It can also include ulcers in the mouth, throat, nose, genitals, and conjunctivitis (red, swollen eyes). The rash can evolve into generalized blisters or skin peeling.

If you have developed Stevens-Johnson syndrome with the use of febuxostat, you should not restart treatment at any time. If you develop a rash or these skin symptoms, go immediately to your doctor and tell them that you are taking this medicine.

If you have a gout attack (a sudden, intense pain accompanied by sensitivity, redness, heat, and swelling of a joint), wait for the attack to subside before starting treatment with febuxostat.

Some people may experience a gout attack when starting to take certain medicines that control uric acid levels. Not everyone experiences these attacks, but they can occur even while taking febuxostat, especially during the first few weeks or months of treatment. It is essential to continue taking febuxostat, as this medicine continues to work to reduce uric acid. If you continue to take febuxostat daily, gout attacks will become less frequent and less painful.

If necessary, your doctor will prescribe other medicines to prevent or treat the symptoms of attacks (such as pain and joint swelling).

In patients with very high levels of urates (e.g., those undergoing chemotherapy for cancer), treatment with medicines to reduce uric acid levels could lead to the accumulation of xanthine in the urinary tract, with possible stone formation, although this has not been observed in patients treated with febuxostat for Tumor Lysis Syndrome.

Your doctor may perform blood tests to check that your liver is working normally.

Children and adolescents

Do not give this medicine to children under 18 years of age, as the safety and efficacy have not been established.

Other medicines and febuxostat

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.

It is especially important that you inform your doctor or pharmacist if you are taking medicines that contain any of the following substances, as they may interact with febuxostat, and your doctor may need to take special precautions:

• Mercaptopurine (used to treat cancer)
• Azathioprine (used to reduce immune response)
• Theophylline (used to treat asthma)

Pregnancy and breastfeeding

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.

It is not known if febuxostat can harm the fetus. Febuxostat should not be used during pregnancy. It is not known if febuxostat passes into breast milk. Do not use febuxostat if you are breastfeeding or planning to breastfeed.

Driving and using machines

Be aware that you may experience dizziness, drowsiness, blurred vision, or numbness or tingling during treatment, so if this happens, do not drive or operate machinery.

Febuxostat Pharma Combix contains lactose and sodium

Febuxostat Pharma Combix tablets contain lactose (a type of sugar). 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 tablet; this is essentially "sodium-free".

3. How to take Febuxostat Pharma Combix

Follow exactly the administration instructions of this medicine given by your doctor. In case of doubt, consult your doctor or pharmacist again.

• The recommended dose is one tablet per day.
• Tablets are taken orally, with or without food.

Febuxostat is available in 80 mg and 120 mg film-coated tablets. Your doctor will prescribe the most suitable dose for you.

Continue taking Febuxostat every day, even if you no longer have gout attacks.

If you take more Febuxostat than you should

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

If you forget to take Febuxostat

If you forget a dose of febuxostat, take it as soon as you remember, unless it is almost time for your next dose; in this case, skip the missed dose and take the next one at the usual time. Do not take a double dose to make up for forgotten doses.

If you stop taking Febuxostat

Even if you feel better, do not stop taking febuxostat unless your doctor tells you to. If you stop taking febuxostat, uric acid levels may increase again, and symptoms may worsen due to the formation of new urate crystals in the joints and kidneys.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop taking this medicine and contact your doctor immediately or go to the nearest hospital if you experience any of the following rare side effects (may affect up to 1 in 1,000 people), as you may experience a severe allergic reaction:

• anaphylactic reactions, hypersensitivity to the medicine (see also section 2 "Warnings and precautions")
• life-threatening skin rashes characterized by blistering and peeling of the skin and mucous membranes, e.g., mouth and genitals, painful ulcers in the mouth and/or genital areas, accompanied by fever, sore throat, and fatigue (Stevens-Johnson syndrome/toxic epidermal necrolysis), or by enlarged lymph nodes, liver enlargement, hepatitis (including liver failure), increased white blood cell count (hypersensitivity to medicines with eosinophilia and systemic symptoms - DRESS syndrome) (see section 2)
• generalized skin rashes.

Common side effects(may affect up to 1 in 10 people):

• abnormal liver test results
• diarrhea
• headache
• rash (including various types of rash, see "uncommon" and "rare" sections below)
• nausea
• increased gout symptoms
• localized swelling due to fluid retention in tissues (edema)
• dizziness
• breathing difficulties
• itching
• pain in the limbs, muscle/joint pain
• fatigue.

Other side effects not mentioned above are included below.

Uncommon side effects(may affect up to 1 in 100 people) include:

• decreased appetite, change in blood sugar levels (diabetes) whose symptom may be excessive thirst, increased blood fats, weight gain
• decreased sex drive
• difficulty sleeping, drowsiness
• numbness, tingling, decreased or altered sensation (hypoesthesia, hemiparesis, or paresthesia), altered sense of taste, decreased sense of smell (hyposmia)
• ECG abnormalities (electrocardiogram), irregular or rapid heartbeat, palpitations
• hot flashes or flushing (redness of the face or neck), increased blood pressure, bleeding (hemorrhage, observed only in patients receiving chemotherapy for blood disorders)
• cough, discomfort or pain in the chest, inflammation of the nasal passages and/or throat (upper respiratory tract infection), bronchitis, lower respiratory tract infection
• dry mouth, abdominal pain or discomfort, gas, upper abdominal pain, heartburn or indigestion, constipation, frequent bowel movements, vomiting, stomach upset
• pruritic rash, urticaria, skin inflammation or discoloration, small red or purple spots on the skin, small bumps on the skin, bumps on the skin covered with small interconnected bumps, rash, bumps, and spots on the skin, increased sweating, night sweats, alopecia, skin redness (erythema), psoriasis, eczema, other skin disorders
• muscle cramps, muscle weakness, bursitis or arthritis (joint inflammation, usually accompanied by pain, swelling, or stiffness), back pain, muscle spasms, muscle and/or joint stiffness
• blood in urine, abnormally frequent urination, abnormal urine tests (increased protein concentration in urine), reduced kidney function, urinary tract infection
• chest pain, chest discomfort
• gallstones or bile duct stones (cholelithiasis)
• increased thyroid-stimulating hormone (TSH) levels in blood
• changes or decrease in urine volume due to kidney inflammation (tubulointerstitial nephritis)
• liver inflammation (hepatitis)
• yellowing of the skin (jaundice)
• bladder infection
• liver damage
• increased creatine phosphokinase levels in blood (an indicator of muscle damage)
• sudden cardiac death
• low red blood cell count (anemia)
• depression
• sleep disorder
• loss of taste
• burning sensation
• vertigo
• circulatory failure
• lung infection (pneumonia)
• mouth ulcers; mouth inflammation
• gastrointestinal perforation
• rotator cuff syndrome
• polymyalgia rheumatica
• feeling of heat
• sudden loss of vision due to blockage of an eye artery.

Rare side effects(may affect up to 1 in 1,000 people) include:

• muscle damage, which can rarely be severe. It can cause muscle problems and, in particular, if you are also feeling unwell or have a high fever, it can be due to abnormal muscle breakdown. Contact your doctor immediately if you experience muscle pain, sensitivity, or weakness
• severe swelling of the deep layers of the skin, especially around the eyes, genitals, hands, feet, or tongue, which can cause sudden difficulty breathing
• high fever accompanied by a rash like measles, enlarged lymph nodes, liver enlargement (including liver failure), increased white blood cell count (leukocytosis, with or without eosinophilia)
• various types of rash (e.g., with white spots with blisters, with pus-filled blisters, with skin peeling), generalized erythema, necrosis, blistering and peeling of the skin and mucous membranes, leading to exfoliation and possible sepsis (Stevens-Johnson syndrome/toxic epidermal necrolysis)
• nervousness
• feeling of thirst
• weight loss, increased appetite, uncontrolled loss of appetite (anorexia)
• muscle and/or joint stiffness
• abnormal blood cell count (white blood cells, red blood cells, or platelets)
• changes or decrease in urine volume due to kidney inflammation (tubulointerstitial nephritis)
• liver inflammation (hepatitis)
• yellowing of the skin (jaundice)
• bladder infection
• liver damage
• increased creatine phosphokinase levels in blood (an indicator of muscle damage)
• sudden cardiac death
• low red blood cell count (anemia)
• depression
• sleep disorder
• loss of taste
• burning sensation
• vertigo
• circulatory failure
• lung infection (pneumonia)
• mouth ulcers; mouth inflammation
• gastrointestinal perforation
• rotator cuff syndrome
• polymyalgia rheumatica
• feeling of heat
• sudden loss of vision due to blockage of an eye artery.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Febuxostat Pharma Combix

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

Do not use this medicine after the expiry date which is stated on the carton and on the blister after EXP. The expiry date is the last day of the month shown.

This medicine does not require any special storage conditions.

Medicines should 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. Container Content and Additional Information

Composition ofFebuxostatPharma Combix 80 mg

The active ingredient is febuxostat. Each film-coated tablet contains 80 mg of febuxostat.

• The other components (excipients) are:
• Tablet core:microcrystalline cellulose, lactose monohydrate, sodium croscarmellose, hydroxypropylcellulose, sodium lauryl sulfate, anhydrous lactose, colloidal anhydrous silica, and magnesium stearate.
• Tablet coating:poly(vinyl alcohol), titanium dioxide (E171), macrogol 3350, talc, and yellow iron oxide (E172).

Appearance of the Product and Container Content

Light yellow or yellow, film-coated, oblong, biconvex tablets, with approximate dimensions of 17.2 mm in length, 6.2 mm in width, and 5.2 mm in thickness, with the engraving "80" on one face and smooth on the other.

Febuxostat Pharma Combix 80 mg is available in PVC/PE/PVDC-Al and PVC/PCTFE-Al blisters in packs of 28 tablets.

Marketing Authorization Holder

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Genepharm S.A.

18th km, Marathonos Ave,

Pallini Attiki, 15351

Greece

Date of the Last Revision of this Leaflet: June 2023

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