Denofix

Patient Information Leaflet: Patient Information

Denofix, 120 mg, coated tablets

Febuxostat

Read the contents of the leaflet carefully before taking the medicine, as it contains important information for the patient.

• 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 symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, please tell your doctor or pharmacist. See section 4.

Table of Contents of the Leaflet

• 1. What is Denofix and what is it 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 pack and other information

1. What is Denofix and what is it used for

Denofix tablets contain the active substance febuxostat and are used to treat gout, which is associated with an excess of a chemical compound called uric acid (urate) in the body. In some patients, the amount of uric acid in the blood increases and may become too high to remain dissolved. In this case, urate crystals may form inside and around the joints and kidneys. The formed crystals can cause sudden, severe pain, redness, warmth, and swelling of the joint (so-called gout attack). If the disease is untreated, larger deposits called tophi may form inside and around the joints. Tophi can cause joint and bone damage. Denofix works by reducing the concentration of uric acid. Maintaining low uric acid levels by taking Denofix once a day prevents the formation of crystals and over time reduces symptoms. Maintaining sufficiently low uric acid levels for a sufficient period may also lead to a reduction in tophi. Denofix 120 mg tablets are also used to treat and prevent high uric acid levels in the blood that may occur during the initiation of cancer chemotherapy. When chemotherapy is used, cancer cells are destroyed, and uric acid levels in the blood increase accordingly, unless uric acid formation is prevented. Denofix is intended for adult patients.

2. Important information before taking Denofix

When not to take Denofix:

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

In case of an allergic reaction to Denofix, stop taking the medicine immediately and contact your doctor or go to the nearest emergency department (see also section 4). Possible symptoms of an allergic reaction are:

• rash, including severe forms of rash (e.g., blisters, nodules, itching, flaking rash), itching;
• swelling of limbs or face;
• breathing difficulties;
• fever and lymph node enlargement;
• life-threatening allergic reactions with cardiac arrest and circulatory failure. The doctor may decide to permanently discontinue treatment with Denofix.

There have been rare reports of potentially life-threatening skin rashes (Stevens-Johnson syndrome) during treatment with febuxostat, initially presenting as red, concentric patches or circular patches, often with blisters, on the trunk. Symptoms may also include ulcers in the mouth, throat, nose, genitals, and conjunctivitis (redness and swelling around the eyes). The rash may spread and cause peeling and separation of the skin. In case of Stevens-Johnson syndrome during treatment with Denofix, treatment with febuxostat should not be restarted. In case of rash or the mentioned skin symptoms, 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 of the joint) before starting treatment with Denofix, wait until the attack subsides. In some people, gout attacks may worsen when starting treatment with certain medicines that control uric acid levels. Worsening does not occur in everyone, but worsening may occur, even if the patient is taking Denofix, especially during the first few weeks or months of treatment. It is essential to continue taking Denofix even if the patient experiences worsening, as Denofix still reduces uric acid levels. Over time, gout attacks will occur less frequently and will be less painful if Denofix is taken daily. The doctor often prescribes other medicines if necessary to help prevent or treat symptoms of worsening gout (such as joint pain and swelling). In patients who have very high uric acid levels (e.g., those undergoing cancer chemotherapy), treatment with uric acid-lowering medicines may lead to the accumulation of xanthine in the urinary tract with the possibility of stone formation, although this has not been observed in patients treated with Denofix for tumor lysis syndrome. The doctor may ask for blood tests to check if liver function is normal.

Children and adolescents

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

Denofix and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take, including those obtained without a prescription. It is particularly important to inform your doctor or pharmacist if you are taking medicines containing any of the following substances, as they may interact with Denofix, and your doctor may consider taking necessary measures:

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

Pregnancy and breastfeeding

It is not known whether Denofix can 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 plans to breastfeed. If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before taking this medicine.

Driving and using machines

Be aware that during treatment, dizziness, drowsiness, blurred vision, and numbness or tingling may occur. 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 previously been diagnosed with intolerance to some sugars, they should contact their doctor before taking the medicine. The medicine contains less than 1 mmol (23 mg) of sodium per tablet, which means the medicine is considered "sodium-free".

3. How to take Denofix

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

• The usual dose of the medicine is one tablet per day. The back of the blister has a marking of the days of the week, making it easier to check if a dose of the medicine has been taken every day.
• The tablets should be taken orally; the medicine can be taken with or without food.

Gout
Denofix is available in 120 mg tablet form. The doctor will prescribe the most suitable dose of the medicine for the patient. Denofix should be taken daily, even if there is no worsening or gout attack. Prevention and treatment of high uric acid levels in patients undergoing cancer chemotherapy
Denofix is available in 120 mg tablet form. Taking Denofix should be started two days before chemotherapy and continued as recommended by the doctor. Treatment is usually short-term.

What to do if you take more Denofix than you should

In case of accidental overdose, ask your doctor for advice or contact the nearest hospital emergency department.

What to do if you miss a dose of Denofix

If a dose of Denofix is missed, it should be taken as soon as the patient remembers, unless it is close to the time for the next dose, in which case the missed dose should be skipped and the next dose taken at the normal time. Do not take a double dose to make up for a missed dose.

What to do if you stop taking Denofix

Do not stop taking Denofix without consulting your doctor, even if you feel better. Stopping treatment with Denofix may cause uric acid levels to increase again, and symptoms may worsen due to the formation of new urate crystals around or in the joints and kidneys. If you have any further questions about taking 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 the medicine and contact your doctor or go to the nearest emergency department immediately if you experience any of the following rare (occurring in 1 in 1,000 patients) side effects, 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 surfaces of the body, such as the mouth and genitals, painful ulcers in the mouth and (or) genitals with fever and lymph node enlargement (Stevens-Johnson syndrome or toxic epidermal necrolysis) or lymph node enlargement, liver enlargement, hepatitis (to liver failure);
• generalized skin rashes.

Common side effects(occurring in less than 1 in 10 patients):

• abnormal liver test results;
• diarrhea;
• headache;
• rash (including various types of rash, see below "uncommon" and "rare");
• nausea;
• worsening of gout symptoms;
• localized swelling due to fluid accumulation in tissues (edema);
• dizziness;
• shortness of breath;
• itching;
• limb pain, muscle pain, or joint pain;
• fatigue.

Other side effects not listed above are listed below.
Uncommon side effects(occurring in less than 1 in 100 patients):

• decreased appetite, changed blood sugar levels (diabetes), which may cause excessive thirst, increased blood fat levels, weight gain;
• decreased libido;
• sleep disorders, drowsiness;
• numbness, tingling, weakness, or changed sensation (hypoesthesia, paresis, or paresthesia), taste disorders, decreased sense of smell (hyposmia);
• abnormalities in the electrocardiogram (ECG) recording of heart activity, irregular or rapid heartbeat, feeling of heartbeat (palpitations);
• hot flashes or flushing (e.g., facial flushing or neck flushing), increased blood pressure, bleeding (hemorrhage, observed only in patients undergoing chemotherapy for blood diseases);
• cough, discomfort or pain in the chest, throat or nasal passage inflammation (upper respiratory tract infection), bronchitis, lower respiratory tract infection;
• dry mouth, abdominal pain or discomfort in the abdomen or gas, upper abdominal pain, heartburn or indigestion, constipation, frequent bowel movements, vomiting, abdominal discomfort;
• itchy rash, hives, skin inflammation, skin discoloration, small, red or purple spots on the skin, small, flat red spots on the skin, flat, red areas on the skin covered with small bumps, rash, localized redness and spots on the skin, excessive sweating, night sweats, hair loss, skin redness (erythema), psoriasis, rash, other types of skin disorders;
• muscle spasms, muscle weakness, bursitis or joint inflammation (arthritis, which is usually accompanied by pain, swelling, and (or) stiffness), back pain, muscle cramps, muscle stiffness and (or) joint stiffness;
• blood in urine, abnormal frequent urination, abnormal urine test results (increased protein in urine), decreased kidney function, urinary tract infection;
• chest pain, discomfort in the chest;
• gallstones or bile duct stones (cholelithiasis);
• increased TSH levels;
• changes in blood chemistry or blood cell count (abnormal blood test results);
• kidney stones;
• erectile dysfunction;
• hypothyroidism;
• blurred vision, changed vision;
• ringing in the ears;
• runny nose;
• mouth ulcers;
• pancreatitis: frequent symptoms include abdominal pain, nausea, and vomiting;
• sudden urge to urinate;
• pain;
• malaise;
• increased INR;
• injury;
• lip swelling.

Rare side effects(occurring in less than 1 in 1,000 patients):

• muscle damage - a condition that can be severe in isolated cases. Muscle disorders may occur, with accompanying malaise or high fever, caused by muscle damage. Contact your doctor immediately if you experience muscle pain, tenderness, or weakness;

and

• severe swelling of the deep layers of the skin, particularly in the area of the lips, eyes, genitals, hands, feet, or tongue, with possible sudden breathing difficulties;
• high fever with a rash, lymph node enlargement, liver enlargement, hepatitis (to liver failure), increased white blood cell count (leukocytosis with or without eosinophilia);
• rashes of various types (e.g., with white spots, blisters, pus-filled blisters, peeling skin, rash), widespread redness, necrosis, blisters on the skin and mucous membranes causing peeling and the possibility of sepsis (Stevens-Johnson syndrome, toxic epidermal necrolysis);
• nervousness;
• feeling thirsty;
• weight loss, increased appetite, uncontrolled loss of appetite (anorexia);
• abnormal, low blood cell count (white or red blood cells or platelets);
• changes in urine or decreased urine output related to kidney inflammation (interstitial nephritis);
• hepatitis;
• jaundice;
• urinary tract infection;
• liver damage;
• increased creatine phosphokinase activity in the blood (a marker of muscle damage);
• sudden cardiac death;
• low red blood cell count (anemia);
• depression;
• sleep disorders;
• taste loss;
• burning sensation;
• vertigo of labyrinthine origin;
• circulatory collapse;
• lung infection (pneumonia);
• mouth ulcers; oral inflammation;
• gastrointestinal perforation;
• rotator cuff syndrome;
• polymyalgia rheumatica syndrome;
• feeling hot;
• sudden loss of vision due to occlusion of an artery in the eye.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, please tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring 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 side effects, you can help provide more information on the safety of this medicine. Side effects can also be reported to the marketing authorization holder.

5. How to store Denofix

• The medicine should be stored out of sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton and blister pack after EXP. The expiry date refers to the last day of the month. The inscription on the packaging after the abbreviation EXP indicates the expiry date, and after the abbreviation Lot/LOT, it indicates the batch number.
• There are no special precautions for storage.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Denofix contains

• The active substance of the medicine is febuxostat. Denofix, 120 mg, coated tablets: Each tablet contains 120 mg of febuxostat.
• The other excipients are: Tablet core:lactose monohydrate, microcrystalline cellulose, hydroxypropyl cellulose, sodium croscarmellose, colloidal silicon dioxide, anhydrous, magnesium stearate. Tablet coating:polyvinyl alcohol, talc, titanium dioxide (E 171), macrogol 3350, methacrylic acid, and ethyl acrylate copolymer (1:1) (Type A), yellow iron oxide (E 172), sodium bicarbonate.

What Denofix looks like and contents of the pack

Denofix, 120 mg, coated tablets: pale yellow or yellow coated tablets in capsule shape with the symbol "120" embossed on one side and smooth on the other, measuring 18.5 mm x 9.0 mm ± 5%. Denofix 120 mg coated tablets are packaged in blisters of aluminum/OPA/aluminum/PVC or aluminum/PVC/PE/PVDC. Denofix 120 mg is available in packs containing 14, 28, 30, 42, 56, 80, 84, and 98 coated tablets. Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Zakłady Farmaceutyczne POLPHARMA S.A. 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 Date of last revision of the leaflet:July 2024