Denofix

Denofix, 120 mg, film-coated tablets
Febuxostatum
Please read the entire leaflet before taking the medicine, as it contains important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

1. What Denofix is and what it is used for
2. Important information before taking Denofix
3. How to take Denofix
4. Possible side effects
5. How to store Denofix
6. Contents of the package and other information

1. What Denofix is and what it is used for

Denofix tablets contain the active substance febuxostat and are used in the treatment of gout,
which is associated with an excess of a chemical compound called uric acid (urate) in the body.
In some patients, the level of uric acid in the blood increases and may become too high for the compound to remain dissolved. In such cases, urate crystals may form within and around the joints and kidneys. These crystals can cause sudden, severe pain, redness, warmth, and swelling of a joint (known as a gout attack). If the disease remains untreated, larger deposits called tophi may form inside and around the joints. Tophi may lead to joint and bone damage.

Denofix works by reducing the concentration of uric acid. Maintaining low uric acid levels through once-daily administration of Denofix stops the formation of crystals and, over time, reduces symptoms. Sustaining sufficiently low uric acid levels for an adequate duration may also lead to a reduction in tophi.

Denofix 120 mg tablets are also used in the treatment and prevention of high blood uric acid levels that may occur at the start of chemotherapy for blood cancer. During chemotherapy, cancer cells are destroyed, leading to a corresponding increase in blood uric acid levels, unless uric acid formation is prevented.

Denofix is intended for adult patients.

2. Important information before using Denofix

When not to use Denofix:

• if the patient is allergic to febuxostat or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Before starting treatment with Denofix, discuss with your doctor:

• if the patient has or has had heart failure, heart problems, or stroke;
• if the patient currently has or has previously had kidney disease and/or severe allergic reactions to allopurinol (a medicine used in the treatment of gout);
• if the patient currently has or has previously had liver disease or abnormal liver function test results;
• if the patient is being treated for high levels of uric acid due to cancer or Lesch-Nyhan syndrome (a rare inherited condition in which there is too much uric acid in the blood);
• if the patient has thyroid problems.

If an allergic reaction to Denofix occurs, treatment should be stopped immediately
(see also section 4). Possible symptoms of an allergic reaction include:

• rash, including severe forms of rash (e.g. blisters, nodules, itchy, peeling rash), itching;
• swelling of limbs or face;
• difficulty breathing;
• fever and swollen lymph nodes;
• severe, life-threatening allergic reactions with cardiac arrest and circulatory collapse. The doctor may decide to permanently discontinue treatment with Denofix.

Rare cases of potentially life-threatening skin rashes (Stevens-Johnson syndrome) have been reported during treatment with febuxostat, initially presenting as reddish, concentric spots or round lesions, often with blisters, on the trunk. Symptoms may also include ulceration of the mouth, throat, nose, genitals, and conjunctivitis (redness and swelling around the eyes). The rash may spread and lead to peeling and detachment of the outer layer of skin.
If Stevens-Johnson syndrome occurs during treatment with Denofix, treatment with febuxostat must not be restarted. If a rash or any of the mentioned skin symptoms occur, contact your doctor immediately and inform them about taking febuxostat.

If the patient experiences a gout attack (sudden onset of severe pain, tenderness, redness, warmth, and swelling in a joint) before starting treatment with Denofix for the first time, wait until the gout attack subsides.
In some people, gout attacks may worsen when starting treatment with certain medicines that control uric acid levels. Flare-ups do not occur in everyone, but they may occur even if the patient is taking Denofix, especially during the first weeks or months of treatment. It is important to continue taking Denofix even if a flare-up occurs, because Denofix continues to reduce uric acid levels. Over time, gout attacks will become less frequent and less painful if Denofix is taken daily.

The doctor may prescribe additional medicines, if necessary, to help prevent or treat symptoms of gout flare-ups (such as joint pain and swelling).

In patients with very high uric acid levels (e.g. those undergoing chemotherapy), treatment with uric acid-lowering medicines may lead to xanthine accumulation in the urinary tract with possible stone formation, although this has not been observed in patients treated with Denofix for tumor lysis syndrome.

The doctor may request blood tests to check whether liver function is normal.

Children and adolescents
Do not use Denofix in children and adolescents under 18 years of age, as the efficacy and safety have not been established.

Denofix with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take, including those obtained without a prescription.

It is especially important to inform your doctor or pharmacist if the patient is taking any medicines containing the following active substances, as they may interact with Denofix, and the doctor may consider taking necessary measures:

• mercaptopurine (used in cancer treatment),
• azathioprine (used to suppress the immune system response),
• theophylline (used in the treatment of asthma).

Pregnancy and breastfeeding
It is not known whether Denofix could harm the unborn child. Denofix should not be used during pregnancy. It is not known whether Denofix passes into breast milk. Denofix should not be used if the patient is breastfeeding or planning to breastfeed.
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult her doctor or pharmacist before using this medicine.

Driving and operating machinery
Be aware that dizziness, drowsiness, blurred vision, and numbness or tingling may occur during treatment. If such symptoms occur, do not drive or operate machinery.

Denofix contains lactose and sodium
Denofix tablets contain lactose (a type of sugar). If the patient has been previously diagnosed with intolerance to certain sugars, the patient should consult their doctor before taking this medicine.

The medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to use Denofix

This medicine should always be taken exactly as prescribed by the doctor. If in doubt, consult
your doctor or pharmacist.

• The usual dose is one tablet per day. The days of the week are marked on the back of the blister pack, which helps to confirm whether the daily dose has been taken.
• Tablets should be taken orally; the medicine can be taken with or without food.

Gout
Denofix is available in 120 mg tablets. The doctor will prescribe the most appropriate dose
for the patient.
Denofix should be taken every day, even if there is no flare-up or acute attack of gout.

Prevention and treatment of high uric acid levels in patients undergoing chemotherapy due to cancer
Denofix is available in 120 mg tablets.
Treatment with Denofix should begin two days before starting chemotherapy and continued as
directed by the doctor. Treatment is usually short-term.

Taking more Denofix than recommended
If an overdose is taken by accident, consult your doctor immediately or contact the nearest
hospital emergency department.

If you miss a dose of Denofix
If a dose of Denofix is missed, 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 a missed dose.

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

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
You should stop taking the medicine and immediately contact a doctor or go to
the nearest emergency department if any of the following rare (occurring in 1 in 1,000
patients) adverse reactions occur, as they may lead to serious allergic reactions:

• anaphylactic reactions, hypersensitivity to the medicine (see also section 2 "Warnings and precautions");
• potentially life-threatening skin rashes characterized by blistering and peeling of the skin and internal mucosal surfaces such as the mouth and genital organs, painful mouth ulcers and (or) genital area accompanied by fever, sore throat, and fatigue (Stevens-Johnson syndrome or 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 rashes.

Common adverse reactions (occur in less than 1 in 10 patients):

• abnormal liver function tests;
• diarrhoea;
• headache;
• rash (including various types of rashes, see below under "not very common" and "rare");
• nausea;
• worsening of gout symptoms;
• localized swelling due to fluid accumulation in tissues (oedema);
• dizziness;
• shortness of breath;
• itching;
• limb pain, muscle or joint pain;
• fatigue.

Other adverse reactions not listed above are listed below.
Not very common adverse reactions (occur in less than 1 in 100 patients):

• decreased appetite, change in blood sugar levels (diabetes), which may present as excessive thirst, increased blood lipid levels, weight gain;
• loss of libido;
• sleep disorders, drowsiness;
• numbness, tingling, weakness, or altered touch sensation (hypoesthesia, paresis, or paraesthesia), taste disturbances, reduced sense of smell (hyposmia);
• abnormalities in heart ECG recording, irregular or rapid heartbeat, palpitations;
• hot flushes or flushing (e.g. redness of face or neck), elevated blood pressure, bleeding (haemorrhage, observed only in patients receiving chemotherapy for blood disorders);
• cough, chest discomfort or pain, inflammation of nasal passages and (or) throat (upper respiratory tract infection), bronchitis, lower respiratory tract infection;
• dry mouth, abdominal pain or discomfort or flatulence, upper abdominal pain, heartburn or indigestion, constipation, more frequent bowel movements, vomiting, stomach discomfort;
• itchy rash, urticaria, dermatitis, skin discoloration, small red or purple spots on the skin, small flat red spots on the skin, flat red areas covered with small bumps, rash, local redness and skin spots, excessive sweating, night sweats, hair loss, skin redness (erythema), psoriasis, eruption, other types of skin disorders;
• muscle cramps, muscle weakness, tendonitis or joint inflammation (arthritis, usually associated with pain, swelling and (or) stiffness), back pain, muscle cramps, muscle and (or) joint stiffness;
• blood in urine, abnormal frequent urination, abnormal urine test results (increased protein in urine), reduced kidney function, urinary tract infection;
• chest pain, chest discomfort;
• gallstones in the gallbladder or bile ducts (cholelithiasis);
• increased TSH levels;
• changes in blood chemistry or number of blood cells or platelets (abnormal blood test results);
• kidney stones;
• erectile dysfunction;
• hypothyroidism;
• blurred vision, vision changes;
• tinnitus;
• nasal congestion;
• mouth ulceration;
• pancreatitis: common symptoms include abdominal pain, nausea and vomiting;
• sudden urge to urinate;
• pain;
• malaise;
• increased INR;
• injury;
• lip swelling.

Rare adverse reactions (occur in less than 1 in 1,000 patients):

• muscle injury - a condition which in isolated cases may be severe. Muscle-related disorders may occur, accompanied by malaise or high
  fever, caused by muscle damage. You should contact a doctor immediately if muscle pain, tenderness or weakness occurs;

• severe swelling of deep skin layers, particularly around the lips, eyes, genitals, hands, feet or tongue, possibly with sudden breathing difficulties;

• high fever with rash resembling measles, swollen lymph nodes, enlarged liver, hepatitis (up to liver failure), increased white blood cell count (leukocytosis with or without eosinophilia);

• various types of rashes (e.g. with white spots, blisters, pustular blisters, skin peeling, measles-like rash), diffuse erythema, necrosis, blisters on skin and mucous membranes leading to separation and risk of sepsis (Stevens-Johnson syndrome, toxic epidermal necrolysis);

• nervousness;

• feeling of thirst;

• weight loss, increased appetite, uncontrolled loss of appetite (anorexia);

• abnormal low number of blood cells (white or red blood cells or platelets);

• changes in urine or reduced urine output associated with kidney inflammation (tubulointerstitial nephritis);

• hepatitis;

• yellowing of the skin (jaundice);

• urinary bladder infection;

• liver damage;

• increased blood creatine phosphokinase activity (a marker of muscle damage);

• sudden death due to cardiovascular causes;

• low number of red blood cells (anaemia);

• depression;

• sleep disorders;

• loss of taste;

• burning sensation;

• vestibular dizziness;

• circulatory collapse;

• lung infection (pneumonia);

• mouth ulceration; inflammation of the mouth;

• gastrointestinal tract perforation;

• rotator cuff syndrome;

• polymyalgia syndrome;

• feeling of warmth;

• sudden vision loss caused by occlusion of an artery in the eye.

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed
in this leaflet, you should inform your doctor or pharmacist.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C,
02-222 Warsaw,
tel.: + 48 22 49 21 301,
fax: + 48 22 49 21 309,
Website: https://smz.ezdrowie.gov.pl
By reporting adverse reactions, more information on the safety of the medicine can be collected.
Adverse reactions can also be reported to the responsible entity.

5. How to store Denofix

• Keep the medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the cardboard box and on the tablet blister foil after the EXP marking. The expiry date refers to the last day of the stated month. The marking on the packaging following EXP indicates the expiry date, and following Lot/LOT indicates the batch number.
• There are no special storage instructions for this medicine.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. Such measures will help protect the environment.

6. Contents of the packaging and other information

What Denofix contains

• The active substance is febuxostat. Denofix 120 mg, coated tablets: Each tablet contains 120 mg of febuxostat.
• Other excipients:
  Tablet core: monohydrate lactose, microcrystalline cellulose, hydroxypropylcellulose, sodium croscarmellose, colloidal anhydrous silica, magnesium stearate.
  Coating: polyvinyl alcohol, talc, titanium dioxide (E 171), macrogol 3350, methacrylic acid copolymer and ethyl acrylate (1:1) (Type A), iron oxide yellow (E 172), sodium hydrogen carbonate.

What Denofix looks like and contents of the pack
Denofix 120 mg, coated tablets: pale yellow or yellow film-coated, capsule-shaped tablets
with the imprint “120” on one side and smooth on the other, measuring
18.5 mm x 9.0 mm ± 5%.
Denofix 120 mg, coated tablets are packed in blisters made of
Aluminium/OPA/Aluminium/PVC or Aluminium/PVC/PE/PVDC.
Denofix 120 mg is available in pack sizes containing 14, 28, 30, 42, 56, 80, 84 and 98
coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
POLPHARMA S.A. Pharmaceutical Works
ul. Pelplińska 19
83-200 Starogard Gdański
tel. + 48 22 364 61 01

Manufacturer
Rontis Hellas Medical and Pharmaceutical Products S.A.
P.O. Box 3012 Larissa Industrial Area
41500 Larissa
Greece

PharOS MT Ltd.
HF62X, Hal Far Industrial Estate
Birzebbugia BBG3000
Malta