FEBUXOSTAT COMBIX 120 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Febuxostat Combix 120 mg film-coated tablets EFG

Read the entire package leaflet carefully before starting to take this medication, as it contains important information for you.

• Keep this package leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed to you only, and you should not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience side effects, consult your doctor or pharmacist, even if they are not listed in this package leaflet. See section 4.

Contents of the package leaflet:

1. What is Febuxostat Combix and what is it used for
2. What you need to know before taking Febuxostat Combix
3. How to take Febuxostat Combix
4. Possible side effects
5. Storage of Febuxostat Combix
6. Package contents and additional information

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

Febuxostat contains the active ingredient febuxostat and is used to treat gout, which is associated with an excess of a chemical compound called uric acid (urate) in the body. 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 the uric acid concentration low by taking febuxostat once a day prevents the formation of crystals and, over time, reduces symptoms. If the uric acid concentration is kept low for a long enough time, the size of the tophi also decreases.

Febuxostat 120 mg tablets are also used in the treatment and prevention of high uric acid levels in the blood, which can occur when chemotherapy is started for the treatment of blood cell cancer.

When chemotherapy is administered, cancer cells are destroyed, and as a result, uric acid levels in the blood increase, unless their formation is prevented.

Febuxostat is for adults.

2. What you need to know before taking Febuxostat Combix

Do not take Febuxostat:

• if you are allergic to febuxostat or any of the other ingredients of this medication (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 or other heart problems
• if you have or have had kidney disease and/or severe allergic reactions to allopurinol (a medication 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 medication (see also section 4).

Possible symptoms of allergic reactions may include:

• rash, including severe forms (e.g., blisters, nodules, exfoliative rashes that itch), itching
• swelling of the limbs or face
• difficulty breathing
• fever with swollen lymph nodes
• also severe allergic reactions that can be life-threatening, associated with cardiac arrest.

Your doctor may decide to permanently discontinue febuxostat treatment.

Rare cases of skin rashes that can be life-threatening (Stevens-Johnson syndrome) have been reported with the use of febuxostat, initially appearing on the trunk as red spots in a target shape or circular spots that often have a blister in the center. It can also include ulcers in the mouth, throat, nose, genitals, and conjunctivitis (red and 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 to the doctor immediately and tell them that you are taking this medication.

If you experience a gout attack (a sudden and 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 medications 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 medication 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 medications to prevent or treat the symptoms of attacks (such as pain and joint swelling).

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

Your doctor may perform blood tests to check that the liver is functioning normally.

Children and adolescents

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

Taking Febuxostat with other medications

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

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

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

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, and numbness or tingling during treatment, so if this happens, do not drive or operate machinery.

Febuxostat Combix contains lactose

Febuxostat Combix tablets contain lactose (a type of sugar). If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

3. How to take Febuxostat Combix

Follow the instructions for administration of this medication indicated 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.

Gout

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

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

Prevention and treatment of high uric acid levels in patients undergoing chemotherapy for cancer

Febuxostat is available in 120 mg tablets.

Start taking febuxostat two days before chemotherapy and continue using it as indicated by your doctor. In general, treatment is short-term.

If you take more Febuxostat than you should

In case of overdose or accidental ingestion, consult your doctor, pharmacist, or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication 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 the next dose; in that case, skip the missed dose and take the next one at the usual time. Do not take a double dose to make up for missed 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 other questions about the use of this medication, ask your doctor or pharmacist.

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone experiences them.

Stop taking this medication 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 medication (see also section 2 "Warnings and precautions")
• skin rashes that can be life-threatening, 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 with swollen lymph nodes, liver enlargement, hepatitis (including liver failure), increased white blood cell count in blood (hypersensitivity to medications with eosinophilia and systemic symptoms - DRESS syndrome) (see section 2)
• widespread 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)

Other side effects not mentioned above are listed below.

The uncommon side effects(may affect up to 1 in 100 people) are:

• 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
• dizziness, numbness, tingling, decreased or altered sensitivity (hypoesthesia, hemiparesis, or paresthesia), altered sense of taste, decreased sense of smell (hyposmia)
• ECG abnormalities (electrocardiogram), irregular or rapid heartbeat, perception of heartbeats (palpitations)
• flushing or redness (redness of the face or neck), increased blood pressure, bleeding (hemorrhage, observed only in patients receiving chemotherapy for blood diseases)
• cough, breathing difficulties, chest discomfort or pain, inflammation of the nasal passages and/or throat (upper respiratory tract infection), bronchitis
• dry mouth, abdominal pain or discomfort, gas, heartburn or indigestion, constipation, more frequent bowel movements, vomiting, stomach discomfort
• itching, hives, skin inflammation or discoloration, small red or purple spots on the skin, small bumps on the skin, skin rash, other skin disorders
• muscle cramps, muscle weakness, muscle and joint pain, bursitis or arthritis (joint inflammation, usually accompanied by pain, swelling, or stiffness), limb pain, back pain, muscle spasms
• blood in urine, abnormal urination, abnormal urine tests (increased protein concentration in urine), reduced kidney function
• fatigue, chest pain, chest discomfort
• gallstones or bile duct stones (cholelithiasis)
• increased thyroid-stimulating hormone (TSH) levels in blood
• changes in blood biochemistry or blood cell count (abnormal blood test results)
• kidney stones
• erectile dysfunction

The rare side effects(may affect up to 1 in 1,000 people) are:

• muscle damage, which can be severe in rare cases. It can cause muscle problems and, particularly if you are feeling unwell or have a high fever, may be due to abnormal muscle destruction. Contact your doctor immediately if you experience muscle pain, sensitivity, or weakness
• severe swelling of the deep skin layers, especially around the lips, eyes, genitals, hands, feet, or tongue, which can cause sudden difficulty breathing
• high fever accompanied by a rash similar to measles, swollen lymph nodes, liver enlargement, hepatitis (including liver failure), increased white blood cell count in blood (leukocytosis, with or without eosinophilia)
• redness of the skin (erythema), different types of rash (e.g., itching, with white spots, with blisters, with peeling skin, measles-like rash), 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
• ringing in the ears
• blurred vision, changes in vision
• hair loss
• mouth ulcers
• pancreatitis: common symptoms are abdominal pain, nausea, and vomiting
• increased sweating
• weight loss, increased appetite, uncontrolled loss of appetite (anorexia)
• muscle and joint stiffness
• abnormal blood cell count (white blood cells, red blood cells, or platelets)
• urgent need to urinate
• changes or decrease in urine volume due to kidney inflammation (tubulointerstitial nephritis)
• liver inflammation (hepatitis)
• yellowish skin (jaundice)
• liver damage
• increased creatine phosphokinase levels in blood (a indicator of muscle damage)

Reporting side effects

If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this package leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medications: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Febuxostat Combix

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date stated on the carton and blister pack after EXP. The expiration date is the last day of the month indicated.

No special storage conditions are required.

Medications should not be disposed of through wastewater or household waste. Deposit the packaging and medications you no longer need at the SIGRE collection point in the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Packaging Content and Additional Information

Composition ofFebuxostatCombix 120 mg

The active ingredient is febuxostat. Each film-coated tablet contains 120 mg of febuxostat.

• The other components (excipients) are:
• Core of the tablet:lactose monohydrate, microcrystalline cellulose (E460i), magnesium stearate (E470b), hydroxypropylcellulose (E463), sodium croscarmellose, anhydrous colloidal silica.
• Tablet coating:Opadry yellow 15B520054 (titanium dioxide (E171), macrogol (E1521), yellow iron oxide (E172), hypromellose (E464), and polysorbate (E433)).

Appearance of the Product and Packaging Content

Light yellow or yellow, film-coated tablets, capsule-shaped, with the engraving "120" on one side and smooth on the other.

Febuxostat Combix 120 mg is available in PVC/Aclar-Al blisters, OPA/Al/PVC-Al blisters, and OPA/Al/PE-Al/PE blisters with a desiccant in packs of 28 tablets.

Only some pack sizes may be marketed.

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

Pharmex Advanced Laboratories S.L.

Ctra. A-431 Km. 19

14720 Almodóvar del Río (Córdoba)

Spain

Date of the Last Revision of this Leaflet: November 2018

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.