FEBUXOSTAT COMBIX 80 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Febuxostat 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 and other information

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

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

Febuxostat 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 severe 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 taking Febuxostat 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 or other heart problems
• 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 limbs or face
• difficulty breathing
• fever with enlarged lymph nodes
• also severe allergic reactions that can put your life in danger, 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 reddish 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 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 immediately to your doctor and tell them that you are taking this medicine.

If you suffer a gout attack (a sudden and severe 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 suffer a gout attack when starting certain medications that control uric acid levels. Not everyone suffers 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 even if you suffer a gout attack, 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 medications to prevent or treat the symptoms of attacks (such as pain and joint swelling).

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.

Taking Febuxostat with other medicines

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 thinking of breastfeeding.

Driving and using machines

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

Febuxostat Combix contains lactose

Febuxostat Combix film-coated 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.

3. How to take Febuxostat Combix

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

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

Febuxostat is marketed in film-coated tablets of 80 mg and 120 mg. 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 Toxicology 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 to take the next one; 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 rise 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”)
• skin rashes that can put your life in danger, characterized by the formation of blisters and peeling of the skin and mucous membranes, for example, 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 in blood (leukocytosis, with or without eosinophilia)
• 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 below “Uncommon” and “Rare” sections)
• nausea
• increased gout symptoms
• localized swelling due to fluid retention in tissues (edema)

Other side effects not mentioned above are included 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)
• abnormalities in the ECG (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, discomfort or pain in the chest, 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 upset
• itching, hives, skin inflammation or discoloration, small red or purple spots on the skin, small bumps on the skin, skin rash covered with small interconnected bumps, rash, hives, and spots on the skin, other skin disorders
• muscle cramps, muscle weakness, muscle and joint pain, bursitis or arthritis (inflammation of the joints, usually accompanied by pain, swelling, or stiffness), pain in the limbs, back pain, muscle spasms
• blood in urine, abnormally frequent urination, abnormal urine tests (increased protein concentration in urine), reduced kidney function
• fatigue, chest pain, chest discomfort
• gallstones or bile duct stones (cholelithiasis)
• increased levels of thyroid-stimulating hormone (TSH) in blood
• changes in blood biochemistry or blood cell count or platelets (abnormal blood test results)
• kidney stones
• difficulty getting an erection

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, in particular, if you also feel unwell or have a high fever, it may be due to abnormal muscle destruction. Contact your doctor immediately if you experience muscle pain, sensitivity, or weakness
• severe swelling of the deep layers of the skin, especially the one surrounding the lips, eyes, genitals, hands, feet, or tongue, which can cause sudden difficulty breathing
• high fever accompanied by a rash similar to measles, enlarged 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 blisters containing pus, with skin peeling, measles-like rash), generalized erythema, necrosis, blistering 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 (interstitial nephritis)
• liver inflammation (hepatitis)
• yellowish skin (jaundice)
• liver damage
• increase in creatine phosphokinase levels in blood (a indicator of muscle damage)

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 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 blister after EXP. The expiry date is the last day of the month shown.

No special storage conditions are required.

Medicines should not be disposed of via wastewater or household waste. Place the empty packaging and any unused medicinal product in the SIGRE collection point at your pharmacy. If you have any doubts, ask your pharmacist how to dispose of the packaging and unused medicinal products. This will help protect the environment.

6. Contents of the pack and other information

Composition of Febuxostat Combix 80 mg

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

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

Appearance of the product and pack contents

Light yellow or yellow film-coated tablets, capsule-shaped, with the engraving “80” on one face and smooth on the other.

Febuxostat Combix 80 mg is presented in PVC/Aclar-Al blisters, OPA/Al/PVC-Al blisters, and OPA/Al/PE-Al/PE blisters with desiccant in packs of 28 tablets.

Marketing authorisation 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 last revision of this leaflet: February 2019

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.