FEBUXOSTAT KRKA 80 mg FILM-COATED TABLETS

2. What you need to know before you take Febuxostat Krka

Do not take Febuxostat Krka

• 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 Krka:

• 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 Krka, stop taking this medicine (see also section 4).

Possible symptoms of allergic reactions could be:

• rash including severe forms (e.g. blisters, nodules, exfoliative rashes that itch), 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 Krka.

Rare cases of skin rashes that can put your life in danger (Stevens-Johnson Syndrome) have been reported with the use of Febuxostat Krka, initially appearing on the trunk as reddish 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 immediately to the doctor and tell them that you are taking this medicine.

If you suffer 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 Krka.

Some people may suffer a gout attack when starting to take certain medicines that control uric acid levels. Not everyone suffers these attacks, but they can occur even while taking Febuxostat Krka, especially during the first weeks or months of treatment. It is essential to continue taking Febuxostat Krka even if you suffer a gout attack, as this medicine continues to work to reduce uric acid. If you continue to take Febuxostat Krka 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 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 Krka 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.

Using Febuxostat Krka with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines, including those obtained without a prescription.

It is especially important that you inform your doctor or pharmacist if you are using medicines that contain any of the following substances, as they may interact with Febuxostat Krka, 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

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

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.

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 Krka contains lactose and sodium

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 Krka

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

• The recommended dose is one tablet per day. The score line or break line on the tablet is only to help you break the tablet in case you have difficulty swallowing it whole.
• The tablets are taken orally, with or without food.

Gout

Febuxostat Krka is available in 80 mg and 120 mg tablets. Your doctor will prescribe the most suitable dose.

Continue to take Febuxostat Krka 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 Krka is available in 120 mg tablets.

Start taking Febuxostat Krka two days before chemotherapy and continue to use it as directed by your doctor. In general, treatment is of short duration.

If you take more Febuxostat Krka than you should

In case of accidental overdose, consult your doctor or go to the nearest emergency center.

If you forget to take Febuxostat Krka

If you miss a dose of Febuxostat Krka, 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 Krka

Even if you feel better, do not stop taking Febuxostat Krka unless your doctor tells you to. If you stop taking Febuxostat Krka, 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 1000 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 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 (leukocytosis, with or without eosinophilia) (see section 2)
• generalized skin rashes

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

• 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 included below.

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 sensation (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, difficulty breathing, 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 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 (joint inflammation, 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 thyroid-stimulating hormone (TSH) levels in blood
• abnormal blood biochemistry or blood cell count (white blood cells, red blood cells, or platelets)
• kidney stones
• erectile dysfunction

Rare side effects(may affect up to 1 in 1000 people) are:

• muscle damage, which can rarely be severe. 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 that 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 (including liver failure), increased white blood cell count (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), generalized erythema, necrosis, blistering and peeling of the skin and mucous membranes, leading to exfoliation and possible sepsis (Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis), or by enlarged lymph nodes, liver enlargement, hepatitis (including liver failure), increased white blood cell count (leukocytosis, with or without eosinophilia)
• 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)
• yellowing of the skin (jaundice)
• liver damage
• increased creatine phosphokinase levels in blood (an indicator of muscle damage)

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Febuxostat Krka

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 packaging after CAD/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. Package Contents and Additional Information

Composition of Febuxostat Krka

• The active ingredient is febuxostat.

Each film-coated tablet contains 80 mg of febuxostat.

Each film-coated tablet contains 120 mg of febuxostat.

• The other ingredients are lactose monohydrate, microcrystalline cellulose, hydroxypropylcellulose, sodium croscarmellose, colloidal hydrated silica, and magnesium stearate in the tablet core, and polyvinyl alcohol, macrogol 3350, titanium dioxide (E171), talc, yellow iron oxide (E172) - only for 120 mg film-coated tablets, and red iron oxide (E172) - only for 80 mg film-coated tablets.

See section 2 "Febuxostat Krka contains lactose and sodium".

Appearance of Febuxostat Krka and Package Contents

Febuxostat Krka 80 mg film-coated tablets (tablets) are pink, oval, biconvex, film-coated, and scored on one side. Tablet dimensions: approximately 16 mm x 8 mm. The score line is only for breaking and facilitating swallowing, but not for dividing into equal doses.

Febuxostat Krka 120 mg film-coated tablets (tablets) are yellow-brown, slightly biconvex, capsule-shaped, film-coated, and scored on both sides. Tablet dimensions: approximately 19 mm x 8 mm. The score line is only for breaking and facilitating swallowing, but not for dividing into equal doses.

Febuxostat Krka is available in boxes of 14, 28, 56, or 84 film-coated tablets in blisters.

Only some pack sizes may be marketed.

Marketing Authorisation Holder

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturers

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

For further information about this medicinal product, please contact the local representative of the marketing authorisation holder.

Date of Last Revision of this Leaflet:

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu