Adenuric

PACKAGE LEAFLET: INFORMATION FOR THE USER

ADENURIC 80 mg film-coated tablets, 120 mg film-coated tablets

Febuxostat
Please 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Never give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What ADENURIC is and what it is used for

ADENURIC tablets contain the active substance febuxostat and are used to treat
gout, a condition associated with excess uric acid (urate) in the body. In some people, the amount of uric acid accumulating in the blood may become so high that it can no longer remain dissolved. In this case, urate crystals may form within and around the joints and kidneys. These crystals can cause sudden, severe pain, redness, warmth, and swelling in a joint (a gout attack). If left untreated, larger deposits called tophi may form within and around the joints. Tophi can damage joints and bones.
ADENURIC works by reducing uric acid levels. Maintaining low uric acid levels through once-daily administration of ADENURIC prevents the accumulation of crystals and, over time, reduces symptoms. If uric acid levels are kept low for a sufficiently long period, existing tophi may even gradually dissolve.
ADENURIC 120 mg tablets are also used for the treatment and prevention of elevated blood levels of uric acid that may occur during chemotherapy for blood cancers.
During chemotherapy, cancer cells are destroyed, leading to increased levels of uric acid in the blood, unless the formation of this acid is prevented.
ADENURIC is for use in adults.

2. What you need to know before taking ADENURIC

Do not take ADENURIC:

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

Warnings and precautions
Talk to your doctor before taking ADENURIC:

• If you have or have had heart failure, heart problems, or a heart attack
• 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 abnormal liver function tests
• If you have high levels of uric acid due to Lesch-Nyhan syndrome (a rare inherited condition in which there is too much uric acid in the blood)
• If you have any thyroid problems.

If allergic reactions to ADENURIC occur, stop treatment with this
medicine (see also section 4).
Possible symptoms of allergic reactions may include:

• Skin rash including severe forms (e.g. blisters, nodules, itchy rash, exfoliative rash), itching
• Swelling of limbs or face
• Difficulty breathing
• Fever with swollen lymph nodes
• Or even severe, life-threatening allergic conditions with cardiac and circulatory arrest. Your doctor may decide to permanently discontinue treatment with ADENURIC.

Rare, life-threatening skin rashes (Stevens-Johnson syndrome) have been reported with the use of ADENURIC,
initially appearing on the trunk as reddish spots or circular lesions, often with central blisters.
These may also include ulcers in the mouth, throat, nose, genitals, and conjunctivitis (red, swollen eyes).
The rash may progress to widespread blistering or skin peeling.
If you have developed Stevens-Johnson syndrome while taking febuxostat, treatment with
ADENURIC must not be restarted. If you develop a skin rash or these skin symptoms,
contact your doctor immediately and inform them that you are being treated with this medicine.
If you are currently experiencing a gout attack (sudden onset of severe pain, tenderness, redness, warmth, and swelling in a joint), wait until the gout attack has subsided before starting treatment with ADENURIC.
In some people, gout attacks may flare up at the beginning of certain treatments used to control uric acid levels. Not everyone experiences flare-ups, but you may experience one even while taking ADENURIC, especially during the first weeks or months of treatment. It is important that you continue taking ADENURIC even during a flare-up, as ADENURIC continues to work to lower your uric acid levels. If you continue taking ADENURIC daily, over time flare-ups will occur less frequently and become less painful.
Often, your doctor may prescribe additional medicines, if needed, to help prevent or treat symptoms of flare-ups (such as pain and swelling in a joint).
In patients with very high urate levels (e.g. patients undergoing chemotherapy), treatment with medicines that lower uric acid levels may lead to xanthine accumulation in the urinary tract, potentially causing kidney stones, although this has not been observed in patients treated with ADENURIC for Tumor Lysis Syndrome.
Your doctor may prescribe blood tests to monitor normal liver function.
Children and adolescents
Do not administer this medicine to children under 18 years of age, as safety and efficacy have not been established.
Other medicines and ADENURIC
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including over-the-counter medicines.
It is very important that you inform your doctor or pharmacist if you are taking a medicine containing any of the following substances, as they may interact with ADENURIC and your doctor may wish to take appropriate measures:

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

Pregnancy and breastfeeding
It is not known whether ADENURIC could harm the fetus. ADENURIC must not be used during
pregnancy. It is not known whether ADENURIC passes into breast milk. You must not take ADENURIC if
you are breastfeeding or planning to breastfeed.
If you are pregnant, think you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Driving and using machines
Be aware that you may experience dizziness, drowsiness, blurred vision,
numbness, or tingling during treatment; if so, do not drive or operate machinery.
ADENURIC contains lactose
ADENURIC tablets contain lactose (a type of sugar). If you know you are intolerant to certain sugars, consult your doctor before taking this medicine.
ADENURIC contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially ‘sodium-free’.

3. How to take ADENURIC

Always take this medicine exactly as directed by your doctor. If you have any doubts, you must consult your doctor or pharmacist.

• The usual dose is one tablet per day. The back of the blister shows the days of the week to help you keep track of whether you have taken your dose each day.
• The tablets should be taken by mouth. They may be taken with or without food.

Chronic hyperuricemia with urate deposition
ADENURIC is available as 80 mg or 120 mg tablets. Your doctor will prescribe the most suitable dosage for you.
Continue taking ADENURIC every day, even in the absence of flare-ups or gout attacks.

Prevention and treatment of high uric acid levels in patients undergoing chemotherapy
ADENURIC is available as 120 mg tablets.
Start taking ADENURIC two days before beginning chemotherapy and continue taking it as advised by your doctor. Treatment is usually of short duration.
The score line on the 80 mg tablet is intended to facilitate breaking the tablet if you have difficulty swallowing it whole.

If you take more ADENURIC than you should
In case of accidental overdose, contact your doctor or the nearest emergency department for advice.

If you forget to take ADENURIC
If you forget to take a dose of ADENURIC, take it as soon as you remember, unless it is almost time for your next dose. In that case, skip the missed dose and take the next dose at the scheduled time. Do not take a double dose to make up for a missed dose.

If you stop taking ADENURIC
Do not stop treatment with ADENURIC without consulting your doctor, even if you feel better. If you stop treatment with ADENURIC, your uric acid levels may start to rise again, and your symptoms may worsen due to the formation of new urate crystals in and around your joints and kidneys.

If you have any questions about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking the medicine and contact your doctor immediately or go to the nearest emergency room if you experience any of the following rare side effects (may affect up to 1 in 1,000 people), as these could be signs of a severe allergic reaction:

• anaphylactic reactions, drug hypersensitivity (see also section 2 "Warnings and Precautions")
• life-threatening skin reactions characterized by blistering and peeling of the skin and internal body surfaces, 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 swollen lymph nodes, enlarged liver, hepatitis (up to liver failure), increased white blood cell count (drug reaction with eosinophilia and systemic symptoms - DRESS) (see section 2).
• generalized skin rash

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

• abnormalities in liver function tests
• diarrhoea
• headache
• skin rash (including various types of rashes, see below under "uncommon" and "rare")
• nausea
• worsening of gout symptoms
• localized swelling due to fluid retention in tissues (oedema)
• dizziness
• shortness of breath
• itching
• limb pain, muscle or joint pain
• fatigue

Other side effects not mentioned above are listed below.
Uncommon side effects (may affect up to 1 in 100 people) are:

• decreased appetite, changes in blood sugar levels (diabetes), one symptom of which may be excessive thirst, increased blood lipid levels, weight gain
• loss of libido (sexual desire)
• difficulty sleeping, drowsiness
• numbness, tingling, reduced or altered sense of touch (hypoesthesia, hemiparesis or paraesthesia), altered taste, reduced sense of smell (hyposmia)
• abnormalities in ECG tracings, irregular or rapid heartbeat, awareness of heartbeat (palpitations)
• hot flushes or flushing (e.g. redness of face or neck), increased blood pressure, bleeding (haemorrhage, observed only in patients undergoing chemotherapy for blood disorders)
• cough, chest pain, inflammation of nasal passages and/or throat (respiratory tract infection), bronchitis, lower respiratory tract infection
• dry mouth, abdominal pain or discomfort, excess intestinal gas, upper abdominal pain, heartburn/dyspepsia, constipation, more frequent defecation, vomiting, gastric discomfort
• itchy skin rash or hives, skin inflammation, change in skin colour, small red or purple spots on the skin, flat red spots on the skin, red area of skin covered with small confluent bumps, skin rashes, areas of redness 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 (inflammation of joints usually accompanied by pain, swelling and/or stiffness), back pain, muscle spasms, muscle and/or joint stiffness
• blood in urine, increased frequency of urination, abnormalities in urine test results (elevated protein levels in urine), reduced kidney function, urinary tract infections
• chest pain, chest discomfort
• gallstones or bile duct stones (cholelithiasis)
• increased blood levels of thyroid-stimulating hormone (TSH)
• changes in blood biochemical test values or red blood cell or platelet counts (abnormal blood test results)
• kidney stones
• difficulty achieving erection
• reduced activity of the thyroid gland
• blurred vision, changes in vision
• ringing in the ears
• runny nose
• mouth ulceration
• inflammation of the pancreas: common symptoms are abdominal pain, nausea and vomiting
• urgency to urinate
• pain
• malaise
• increased INR (a measure of blood clotting)
• bruising
• swelling of the lips

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

• muscle damage, a condition which in rare cases may be severe. Muscle problems may develop, and particularly if you also feel unwell or have high fever, this could be due to abnormal breakdown of muscle cells. Contact your doctor immediately if you experience muscle pain, tenderness or weakness
• marked swelling of deeper layers of the skin, especially around the eyes, genitals, hands, feet or tongue, possibly with sudden difficulty breathing
• high fever associated with measles-like rash, swollen lymph nodes, enlarged liver, hepatitis (up to liver failure), increased white blood cell count (leucocytosis, with or without eosinophilia)
• skin rashes of various types (e.g. with white spots, blisters, pus-filled blisters, skin peeling, measles-like rash), widespread erythema, necrosis and blistering detachment of the epidermis and mucous membranes, leading to exfoliation and possible sepsis (Stevens-Johnson syndrome/toxic epidermal necrolysis)
• nervousness
• thirst
• weight loss, increased appetite, uncontrolled loss of appetite (anorexia)
• abnormally low levels of blood cells (white blood cells or red blood cells or platelets)
• changes or decreased amount of urine due to kidney inflammation (tubulo-interstitial nephritis)
• liver inflammation (hepatitis)
• yellowing of the skin (jaundice)
• bladder infection
• liver damage
• increased levels of creatine phosphokinase in the blood (a marker of muscle damage)
• sudden cardiac death
• low number of red blood cells (anaemia)
• depression
• sleep disorders
• loss of taste
• burning sensation
• dizziness
• circulatory failure
• lung infection (pneumonia)
• mouth ulcers; inflammation of the mouth
• gastrointestinal perforation
• rotator cuff syndrome
• polymyalgia rheumatica
• feeling of warmth
• sudden loss of vision due to blockage of an artery in the eye

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store ADENURIC

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton and on the tablet blister foil after "EXP". The expiry date refers to the last day of the month.
• This medicine does not require any special storage conditions.

Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What ADENURIC contains
The active substance is febuxostat.
Each tablet contains 80 mg or 120 mg of febuxostat.
The excipients are:
Tablet core: monohydrate lactose, microcrystalline cellulose, magnesium stearate,
hydroxypropylcellulose, sodium croscarmellose, hydrated colloidal silica.
Tablet coating: Opadry II yellow, 85F42129 containing: polyvinyl alcohol, titanium
dioxide (E171), macrogol type 3350, talc, yellow iron oxide (E172).

What ADENURIC looks like and contents of the pack
ADENURIC film-coated tablets are pale yellow/yellow in colour and capsule-shaped.
The 80 mg film-coated tablets have the number '80' engraved on one side and a score line on the other side. The 120 mg film-coated tablets have the number '120' engraved on one side.
ADENURIC 80 mg and 120 mg is packed in transparent blisters (Aclar/PVC/Aluminium or PVC/PE/PVDC/Aluminium) containing 14 tablets.
ADENURIC 80 mg and 120 mg is available in packs of 14, 28, 42, 56, 84 and 98 film-coated tablets.
It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Menarini International Operations Luxembourg S.A.
1, Avenue de la Gare, L-1611 Luxembourg
Luxembourg

Manufacturers
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 Authorisation Holder:

België/Belgique/Belgien Lietuva
Menarini Benelux NV/SA UAB “BERLIN-CHEMIE MENARINI
Tél/Tel: + 32 (0)2 721 4545 BALTIC”
Tel: +370 52 691 947

България Luxembourg/Luxemburg
“Берлин-Хеми / А. Менарини България” EOOD Menarini Benelux NV/SA
тел.: +359 2 454 0950 Tél/Tel: + 32 (0)2 721 4545

Česká republika Magyarország
Berlin-Chemie/A.Menarini Ceska republika s.r.o. Berlin-Chemie/A. Menarini Kft.
Tel: +420 267 199 333 Tel.: +36 1799 7320

Danmark Malta
Pharmaprim AB Menarini International Operations Luxembourg
Tlf: +468355933 S.A.
Tel: +352 264976

Deutschland Nederland
Berlin-Chemie AG Menarini Benelux NV/SA
Tel: +49 (0) 30 67070 Tel: +32 (0)2 721 4545

Eesti Norge
OÜ Berlin-Chemie Menarini Eesti Pharmaprim AB
Tel: +372 667 5001 Tlf: +468355933

Ελλάδα Österreich
MENARINI HELLAS AE A. Menarini Pharma GmbH.
Τηλ: +30 210 8316111-13 Tel: +43 1 879 95 85-0

España Polska
Laboratorios Menarini S.A. Berlin-Chemie/Menarini Polska Sp. z o.o.
Tel: +34-93 462 88 00 Tel.: +48 22 566 21 00

France Portugal
MENARINI France A. Menarini Portugal – Farmacêutica, S.A.
Tél: +33 (0)1 45 60 77 20 Tel: +351 210 935 500

Hrvatska România
Berlin-Chemie Menarini Hrvatska d.o.o. Berlin-Chemie A. Menarini S.R.L.
Tel: + 385 1 4821 361 Tel: +40 21 232 34 32

Ireland Slovenija
A. Menarini Pharmaceuticals Ireland Ltd Berlin-Chemie / A. Menarini Distribution
Tel: +353 1 284 6744 Ljubljana d.o.o.
Tel: +386 01 300 2160

Ísland Slovenská republika
Pharmaprim AB Berlin-Chemie / A. Menarini Distribution
Sími: +468355933 Slovakia s.r.o
Tel: +421 2 544 30 730

Italia Suomi/Finland
A. Menarini Industrie Farmaceutiche Riunite s.r.l. Berlin-Chemie/A.Menarini Suomi OY
Tel: +39-055 56801 Puh/Tel: +358 403 000 760

Κύπρος Sverige
MENARINI HELLAS AE Pharmaprim AB
Τηλ: +30 210 8316111-13 Tel: ++468355933

Latvija United Kingdom (Northern Ireland)
SIA Berlin-Chemie/Menarini Baltic A. Menarini Farmaceutica Internazionale S.R.L.
Tel: +371 67103210 Tel: +44 (0)1628 856400

This leaflet was last revised on

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu