Denofix

Patient Information Leaflet: Patient Information

Denofix, 80 mg, Coated Tablets

Febuxostat

Read the contents of the leaflet before taking the medicine because it contains important information for the patient.

• Keep this leaflet, so you can read it again if you need to.
• In case of any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed to you by a doctor. 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, 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 excessive levels 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 such cases, 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 left untreated, larger deposits called tophi may form inside and around the joints. Tophi can cause joint and bone damage. Denofix works by reducing uric acid levels. Maintaining low uric acid levels by taking Denofix once daily prevents the formation of crystals and, over time, reduces symptoms. Maintaining sufficiently low uric acid levels for a long enough period may also lead to a reduction in tophi. Denofix is intended for adult patients.

2. Important information before taking Denofix

When not to take Denofix:

• if you are 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 you have or have had heart failure, heart problems, or stroke;
• if you currently have or have had kidney or liver disease, or severe allergic reactions to allopurinol (a medicine used to treat gout);
• if you currently have or have had liver disease or abnormal liver function tests;
• if you are 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 you have thyroid problems.

In case of an allergic reaction to Denofix, stop taking the medicine immediately (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 swollen lymph nodes;
• life-threatening allergic reactions with cardiac arrest and circulatory collapse. 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 round patches, often with blisters, on the torso. 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 a rash or the mentioned skin symptoms, you should immediately contact your doctor and inform them about taking febuxostat. If you have 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 may not occur in everyone, but worsening may occur, even if you are taking Denofix, especially during the first few weeks or months of treatment. It is essential to continue taking Denofix even if you experience worsening because Denofix still reduces uric acid levels. Over time, gout attacks will become less frequent and less painful if Denofix is taken daily. Your doctor may prescribe other medicines if necessary to help prevent or treat symptoms of worsening gout (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 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 due to tumor lysis syndrome. Your doctor may ask you to have blood tests to check if your liver is working properly.

Children and adolescents

Do not use Denofix 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 or have recently taken, as well as any medicines you plan to take, including those available 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 an 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 you are breastfeeding or plan to breastfeed. If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your 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 you experience such symptoms, do not drive or operate machinery.

Denofix contains lactose and sodium

Denofix tablets contain lactose (a type of sugar). If you have previously been diagnosed with intolerance to some sugars, you should contact your 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, consult your doctor or pharmacist.

• The usual dose of Denofix is one tablet per day. The back of the blister pack has a marking of the days of the week, making it easier to check if you have taken your daily dose.
• Take the tablets orally; the medicine can be taken with or without food.

Gout
Denofix is available in 80 mg tablet form. Your doctor will prescribe the most suitable dose for you. Denofix should be taken daily, even if you do not experience a gout attack or worsening. Your doctor may prescribe other medicines if necessary to help prevent or treat symptoms of worsening gout (such as joint pain and swelling).

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 you miss a dose of Denofix, take it as soon as you remember, unless it is close to the time for your next dose, in which case skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up for the 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 rise again, and symptoms may worsen due to the formation of new urate crystals around the joints or in the joints and kidneys. If you have any further doubts about taking this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Denofix 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 the following rare (occurring in 1 in 1000 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, sore throat, and fatigue (Stevens-Johnson syndrome or toxic epidermal necrolysis) or swollen lymph nodes, liver enlargement, hepatitis (leading to liver failure), elevated white blood cell count (drug reaction with eosinophilia and systemic symptoms - DRESS) (see section 2);
• generalized skin rashes.

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

• abnormal liver function tests;
• 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, changes in blood sugar levels (diabetes), which may cause excessive thirst, increased blood lipid levels, weight gain;
• decreased libido;
• sleep disturbances, drowsiness;
• numbness, tingling, weakness, or changes in touch sensation (hypoesthesia, paresis, or paresthesia), taste disturbances, decreased sense of smell (hyposmia);
• abnormalities in the electrocardiogram (ECG) recording of heart activity, irregular or rapid 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, nasal or throat inflammation (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 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, eczema, other types of skin disorders;
• muscle spasms, muscle weakness, bursitis or tendonitis (joint inflammation, 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 (elevated protein levels 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, changes in vision;
• ringing in the ears;
• runny nose;
• mouth ulcers;
• pancreatitis: common 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 1000 patients):

• muscle damage, a condition that can be severe in isolated cases. Muscle disorders may occur, with concurrent malaise or high fever, caused by muscle damage. Contact your doctor immediately if you experience muscle pain, tenderness, or weakness;
• severe swelling of the deep layers of the skin, particularly in the lips, eyes, genitals, hands, feet, or tongue, with possible sudden breathing difficulties;
• high fever with a rash, swollen lymph nodes, liver enlargement, hepatitis (leading to liver failure), elevated 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 possible sepsis (Stevens-Johnson syndrome, toxic epidermal necrolysis);

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• nervousness;
• thirst;
• 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 (indicator of muscle damage);
• sudden cardiac death;
• low red blood cell count (anemia);
• depression;
• sleep disturbances;
• taste loss;
• burning sensation;
• vertigo;
• cardiovascular collapse;
• lung infection (pneumonia);
• mouth ulcers; oral inflammation;
• gastrointestinal perforation;
• rotator cuff syndrome;
• polymyalgia rheumatica;
• feeling of heat;
• sudden loss of vision due to blockage of an artery in the eye.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, 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

• Keep the medicine out of the 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 EXP means the expiry date, and after Lot/LOT means the batch number.
• There are no special precautions for storing the medicine.

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

6. Contents of the pack and other information

What Denofix contains

• The active substance of Denofix is febuxostat. Denofix, 80 mg, coated tablets: Each tablet contains 80 mg of febuxostat.
• The other excipients are: Tablet core:lactose monohydrate, microcrystalline cellulose, hydroxypropylcellulose, 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, 80 mg, coated tablets: pale yellow or yellow coated tablets in a capsule shape with the symbol "80" embossed on one side and smooth on the other, measuring 16.5 mm x 7.0 mm ± 5%. Denofix 80 mg, coated tablets are packaged in blisters of aluminum/OPA/aluminum/PVC or aluminum/PVC/PE/PVDC. Denofix 80 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