ADENURIC 120 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

ADENURIC 80mg film-coated tablets.

ADENURIC 120mg film-coated tablets.

febuxostat

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

1. What is ADENURIC and what is it used for

ADENURIC tablets contain the active substance febuxostat and are 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 (this is 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.

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

ADENURIC 120 mg tablets are also used in the treatment and prevention of high levels of uric acid 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.

ADENURIC is for adults.

2. What you need to know before you take ADENURIC

Do not take ADENURIC

• 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 ADENURIC:

• if you have or have had heart failure, 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 ADENURIC, 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 swollen lymph nodes
• also life-threatening allergic reactions associated with cardiac arrest.

Your doctor may decide to permanently discontinue treatment with ADENURIC.

Rare cases of skin rash that can be life-threatening (Stevens-Johnson Syndrome) have been reported with the use of ADENURIC, 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 to the doctor immediately and tell them that you are taking this medicine.

If you experience a gout attack (severe pain that starts suddenly accompanied by sensitivity, redness, heat, and swelling of a joint), wait for the attack to subside before starting treatment with ADENURIC.

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 ADENURIC, especially during the first few weeks or months of treatment. It is essential to continue taking ADENURIC, as this medicine continues to work to reduce uric acid. If you continue to take ADENURIC 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 decrease 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 ADENURIC 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 ADENURIC 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 ADENURIC, and your doctor may need to take special precautions:

• mercaptopurine (used to treat cancer)
• azathioprine (used to reduce the immune response)
• theophylline (used to treat asthma)

Pregnancy and breastfeeding

It is not known if ADENURIC can harm the fetus. ADENURIC should not be used during pregnancy. It is not known if ADENURIC passes into breast milk. Do not use ADENURIC 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.

ADENURIC contains lactose

ADENURIC 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.

ADENURIC contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; this is essentially "sodium-free".

3. How to take ADENURIC

Take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.

• The recommended dose is one tablet per day. The blister pack has the days of the week printed on the back to help you check that you take your dose every day.
• Tablets are taken orally, with or without food.

Gout

ADENURIC is available in 80 mg and 120 mg tablets. Your doctor will prescribe the most suitable dose for you.

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

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

ADENURIC is available in 120 mg tablets.

Start taking ADENURIC two days before chemotherapy and continue using it as directed by your doctor. Treatment is usually short-term.

The score line on the 80 mg tablet is only to help you break the tablet if you find it difficult to swallow whole.

If you take more ADENURIC than you should

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

If you forget to take ADENURIC

If you miss a dose of ADENURIC, 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 ADENURIC

Even if you feel better, do not stop taking ADENURIC unless your doctor tells you to. If you stop taking ADENURIC, 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 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 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 by swollen 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)
• widespread skin rash

The 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)
• dizziness
• breathing difficulties
• itching
• pain in the limbs, muscle/joint pain
• fatigue

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
• 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)
• hot flashes or flushing (redness of the face or neck), increased blood pressure, bleeding (hemorrhage, observed only in patients receiving chemotherapy for blood diseases)
• 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
• itchy rash, hives, 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, hair loss, 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)
• abnormal blood biochemistry or blood cell count (including white blood cells, red blood cells, or platelets)
• kidney stones
• erectile dysfunction
• decreased thyroid gland activity
• blurred vision, changes in vision
• ringing in the ears
• runny nose
• mouth ulcers
• pancreatitis: common symptoms are abdominal pain, nausea, and vomiting
• urgent need to urinate
• pain
• discomfort
• increased INR
• bruising
• swelling of the lips

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

• muscle damage, which can be severe in rare cases. It can cause muscle problems and, particularly if you 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 around the 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 (leukocytosis, with or without eosinophilia)
• various types of rash (e.g. with white spots with blisters, with pus-filled blisters, with skin peeling, measles-like rash), generalized redness, 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)
• yellowish 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
• dizziness
• circulatory failure
• lung infection (pneumonia)
• mouth sores; 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, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through 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. Storing ADENURIC

• 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 refers to the last day of the month shown.
• This medicine does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Package Contents and Additional Information

ADENURIC Composition

The active ingredient is febuxostat.

Each tablet contains 80 mg or 120 mg of febuxostat.

The other components are:

Tablet core:lactose monohydrate, microcrystalline cellulose, magnesium stearate, hydroxypropylcellulose, sodium croscarmellose, hydrated colloidal silica.

Tablet coating:Opadry II yellow 85F42129, which contains: polyvinyl alcohol, titanium dioxide (E171), macrogoles 3350, talc, yellow iron oxide (E172).

Product Appearance and Package Contents

ADENURIC film-coated tablets are yellow or light yellow capsule-shaped tablets.

The 80 mg film-coated tablets are marked with "80" on one side and have a score line on the other side. The 120 mg film-coated tablets are marked with "120" on one side.

ADENURIC 80 mg and 120 mg are available in transparent blisters (Aclar/PVC/Aluminum or PVC/PE/PVDC/Aluminum) of 14 tablets.

ADENURIC 80 mg and 120 mg are available in packs of 14, 28, 42, 56, 84, and 98 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Menarini International Operations Luxembourg S.A.

1, Avenue de la Gare, L-1611 Luxembourg

Luxembourg

Manufacturer:

Patheon France

40 boulevard de Champaret

38300 Bourgoin Jallieu

France

or

Menarini - Von Heyden GmbH

Leipziger Strasse 7-13

01097 Dresden

Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder.

Date of the Last Revision of this Leaflet:

Other Sources of Information

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