Pazopanib tzf

Package leaflet: Information for the patient

Pazopanib TZF, 200 mg, coated tablets
Pazopanib TZF, 400 mg, coated tablets
Pazopanib
Please read carefully all the information in this leaflet before taking the medicine, as it contains
important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any doubts, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any possible adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents:

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

1. What Pazopanib TZF is and what it is used for

Pazopanib TZF belongs to a group of medicines called protein kinase inhibitors. The medicine works by inhibiting the activity of proteins involved in the growth and spread of cancer cells.
Pazopanib TZF is used in adults to treat:

• advanced or metastatic renal cell carcinoma (kidney cancer).
• certain types of soft tissue sarcoma, which is a type of tumour affecting the body's connective tissue. It may occur in muscles, blood vessels, fatty tissue, or other tissues that support, surround, and protect internal organs.

2. Important information before using Pazopanib TZF

When not to use Pazopanib TZF

• if the patient is allergic to pazopanib or to any of the other ingredients of this medicine (listed in section 6). The patient should consult a doctor if they think this applies to them.

Warnings and precautions
Before starting treatment with Pazopanib TZF, discuss with the doctor:

• if the patient has a heart disease.
• if the patient has a liver disease.
• if the patient has had heart failure or heart attack.
• if the patient has a history of pneumothorax (collapsed lung).
• if the patient has bleeding, blood clots, or arterial narrowing.
• if the patient has had stomach or intestinal disorders, such as perforation (a hole in the wall of the stomach or intestine) or fistula (an abnormal connection between different parts of the intestine).
• if the patient has thyroid disorders.
• if the patient has kidney function disorders.
• if the patient has or has previously had an aneurysm (a bulge and weakening of a blood vessel wall) or a tear in the wall of a blood vessel. The patient should inform the doctor if any of these conditions apply. The doctor will decide whether Pazopanib TZF is suitable for the patient. The patient may need to undergo additional tests to check whether the kidneys, heart, and liver are functioning properly.

High blood pressure and the use of Pazopanib TZF
Pazopanib TZF may cause increased blood pressure. Blood pressure will be monitored before starting treatment with Pazopanib TZF and during treatment.
If the patient develops high blood pressure, the doctor will prescribe medications to lower blood pressure.

• The patient should inform the doctor if they have high blood pressure.

If the patient is scheduled for surgery
The doctor will advise stopping treatment with Pazopanib TZF at least 7 days before surgery, as the medicine may affect wound healing after surgery. Treatment will be resumed once the wound has healed.

Conditions requiring special attention
Pazopanib TZF may worsen certain conditions or cause serious side effects. While taking Pazopanib TZF, it is essential to pay attention to certain symptoms to reduce the risk of adverse effects. See section 4.

Children and adolescents
Pazopanib TZF is not recommended for patients under 18 years of age. The effect of the medicine in this patient group has not yet been established. For safety reasons, the medicine should not be used in children under 2 years of age.

Pazopanib TZF and other medicines
Tell the doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines they plan to take. This includes herbal medicines and other medicines available without a prescription.

Some medicines may affect the action of Pazopanib TZF or increase the likelihood of side effects. Pazopanib TZF may also affect the action of other medicines. These include:

• clarithromycin, ketoconazole, itraconazole, rifampicin, telithromycin, voriconazole (used to treat infections).
• atazanavir, indinavir, nelfinavir, ritonavir, saquinavir (used to treat HIV infection).
• nefazodone (used to treat depression).
• simvastatin and possibly other statins (used to treat high blood cholesterol).
• medicines reducing gastric acid secretion. Medicines taken to reduce stomach acid (e.g. proton pump inhibitors, H\2-receptor antagonists, or antacids) may affect how Pazopanib TZF is absorbed. Advice should be sought from the doctor or nurse.

The patient should tell the doctor or pharmacist if they are taking any of these medicines.

Pazopanib TZF with food and drink
Do not take Pazopanib TZF with food, as this affects the absorption of the medicine. The medicine should be taken at least two hours after a meal or one hour before a meal (see section 3).
During treatment with Pazopanib TZF, do not drink grapefruit juice, as this may increase the risk of side effects.

Pregnancy, breastfeeding, and fertility
Pazopanib TZF is not recommended during pregnancy. It is unknown how Pazopanib TZF affects pregnancy.

• The patient should inform the doctor if she is pregnant or planning to become pregnant.
• While taking Pazopanib TZF and for at least 2 weeks after stopping treatment, an effective method of contraception should be used to prevent pregnancy.
• The patient should inform the doctor if she becomes pregnant while taking Pazopanib TZF.

Breastfeeding must not be performed while taking Pazopanib TZF. It is unknown whether the components of Pazopanib TZF pass into human milk. Discuss this with the doctor.

Men (including men who have had a vasectomy), whose partners are pregnant or may become pregnant (including women using other contraceptive methods), should use condoms during sexual intercourse while taking Pazopanib TZF and for at least 2 weeks after the last dose.

Treatment with Pazopanib TZF may affect fertility. Discuss this with the doctor.

Driving and operating machinery
Side effects may occur while taking Pazopanib TZF that could affect the ability to drive or operate machinery.

• Driving and operating machinery should be avoided if the patient experiences dizziness, fatigue, weakness, or reduced energy levels.

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

3. How to take Pazopanib TZF

This medicine should always be taken exactly as prescribed by your doctor. If in doubt,
consult your doctor or pharmacist.
How many tablets to take
The usual dose is two tablets of Pazopanib TZF 400 mg (800 mg of pazopanib)
taken once daily. The 800 mg dose is the maximum daily dose. Your doctor may recommend
reducing the dose if you experience adverse effects.
When to take the medicine
Do not take Pazopanib TZF with food. The medicine should be taken at least two
hours after a meal or one hour before a meal. For example, the medicine can be taken two
hours after breakfast or one hour before lunch. Pazopanib TZF should be taken
at the same time each day.
Tablets should be swallowed whole, one after the other, with water. Do not break or crush the tablets, as this affects the absorption of the medicine and may increase the risk of adverse effects.
Taking more Pazopanib TZF than prescribed
If you have taken more tablets than prescribed, you should seek advice from your doctor or
pharmacist. If possible, show the medicine package or this leaflet.
Missing a dose of Pazopanib TZF
Do not take a double dose to make up for a missed dose. Take the next dose at the usual time.
Do not stop taking Pazopanib TZF without consulting your doctor
Pazopanib TZF should be taken for as long as prescribed by your doctor. Do not discontinue treatment unless instructed by your doctor.

4. Possible adverse effects

Like any medicine, this medicine can cause adverse effects, although not everyone will experience them.

Possible serious adverse effects

Brain swelling (reversible posterior leukoencephalopathy syndrome)
Rarely, Pazopanib TZF may cause brain swelling, which can be life-threatening. Symptoms include:

• loss of speech
• vision disturbances
• seizure (fits)
• disorientation
• high blood pressure
  Stop taking Pazopanib TZF and seek immediate medical help if any of these symptoms occur, or if headache occurs together with any of these symptoms.

Hypertensive crisis (sudden and severe increase in blood pressure)
Pazopanib TZF may occasionally cause a sudden and severe rise in blood pressure. This condition is known as hypertensive crisis. Your doctor will monitor your blood pressure during treatment with Pazopanib TZF. Symptoms of hypertensive crisis may include:

• severe chest pain
• severe headache
• blurred vision
• confusion
• nausea
• vomiting
• severe anxiety
• shortness of breath
• seizure (fits)
• fainting
  Stop taking Pazopanib TZF and seek immediate medical help if a hypertensive crisis occurs.

Heart problems
The risk of these problems may be higher in people with existing heart disease or those taking other medicines. While taking Pazopanib TZF, you will be monitored for heart problems.

Heart rhythm disorders/heart failure, heart attack
Pazopanib TZF may affect the heart's ability to pump blood or may increase the risk of heart attack. Symptoms include:

• irregular or rapid heartbeat
• rapid fluttering of the heart
• fainting
• pain or pressure in the chest
• pain in arms, back, neck, or jaw
• shortness of breath
• swelling of the legs
  Seek immediate medical help if any of these symptoms occur.

Changes in heart rhythm (QT interval prolongation)
Pazopanib TZF may affect heart rhythm, which in some people may lead to heart rhythm disorders called torsade de pointes, which can be serious. These may cause a very rapid heartbeat, potentially leading to loss of consciousness.
Inform your doctor if you experience changes in heart rhythm, such as a heartbeat that is too fast or too slow.

Stroke
Pazopanib TZF may increase the risk of stroke. Symptoms of stroke may include:

• numbness or weakness on one side of the body
• difficulty speaking
• headache
• dizziness
  Seek immediate medical help if any of these symptoms occur.

Bleeding
Pazopanib TZF may cause severe bleeding from the gastrointestinal tract (from the stomach, oesophagus, rectum or intestines), lungs, kidneys, mouth, vagina, or bleeding into the brain, although this is not common. Symptoms of bleeding include:

• presence of blood in stool or black-coloured stool
• blood in urine
• abdominal pain
• coughing up blood or vomiting blood
  Seek immediate medical help if any of these symptoms occur.

Perforation and fistula
Pazopanib TZF may cause a tear (perforation) in the wall of the stomach or intestine or the formation of an abnormal connection between two parts of the gastrointestinal tract (fistula). Symptoms may include:

• severe abdominal pain
• nausea and (or) vomiting
• fever
• formation of an opening (perforation) in the stomach, large or small intestine, from which blood-stained or foul-smelling pus leaks
  Seek immediate medical help if any of these symptoms occur.

Liver problems
Pazopanib TZF may cause liver disorders, which may lead to serious conditions such as impaired liver function or liver failure, which may be fatal. Your doctor will monitor your liver enzyme activity during treatment with Pazopanib TZF. Symptoms indicating impaired liver function may include:

• yellowing of the skin or whites of the eyes (jaundice)
• dark-coloured urine
• feeling tired
• nausea
• vomiting
• loss of appetite
• pain on the right side of the abdomen
• easy bruising
  Seek immediate medical help if any of these symptoms occur.

Blood clots
Deep vein thrombosis and pulmonary embolism
Pazopanib TZF may cause blood clots in veins, especially in the legs (deep vein thrombosis), which may also travel to the lungs (pulmonary embolism). Symptoms may include:

• sudden chest pain
• shortness of breath
• rapid breathing
• leg pain
• swelling of arms and hands or hands and feet

Thrombotic microangiopathy
Pazopanib TZF may cause blood clots in small blood vessels in the kidneys and brain, associated with a decrease in red blood cells and platelets (thrombotic microangiopathy). Symptoms include:

• easy bruising
• high blood pressure
• fever
• confusion
• drowsiness
• seizure (fits)
• reduced urine output
  Seek immediate medical help if any of these symptoms occur.

Tumour lysis syndrome
Pazopanib TZF may cause rapid breakdown of tumour cells, leading to tumour lysis syndrome, which may be fatal in some patients. Symptoms may include irregular heartbeat, seizure (fits), confusion, muscle cramps, or reduced urine output. Seek immediate medical help if any of these symptoms occur.

Infections
Infections occurring during treatment with Pazopanib TZF may become severe. Symptoms of infection may include:

• fever
• flu-like symptoms such as cough, fatigue, and body aches that do not resolve
• shortness of breath and (or) wheezing
• pain during urination
• cuts, scratches, or wounds that are red, warm, swollen, or painful
  Seek immediate medical help if any of these symptoms occur.

Lung inflammation
Pazopanib TZF may rarely cause lung inflammation (interstitial lung disease, pneumonia), which may be fatal in some patients. Symptoms include shortness of breath or persistent cough. While taking Pazopanib TZF, you will be monitored for any lung disorders.
Seek immediate medical help if any of these symptoms occur.

Thyroid disorders
Pazopanib TZF may reduce the production of thyroid hormones in the body. This may lead to weight gain and fatigue. During treatment with Pazopanib TZF, your doctor will monitor your thyroid hormone levels.
Tell your doctor if you notice significant weight gain or fatigue.

Blurred vision or visual disturbances
Pazopanib TZF may cause detachment or tear of the membrane at the back of the eye (retinal detachment or tear). This may cause blurred vision or visual disturbances.
Inform your doctor if you notice any changes in vision.

Possible adverse effects (including possible serious adverse effects in appropriate frequency categories)

Very common adverse effects (may occur in more than 1 in 10 patients):

• high blood pressure
• diarrhoea
• nausea or vomiting
• abdominal pain
• loss of appetite
• weight loss
• taste disturbances or loss of taste
• mouth pain
• headache
• tumour pain
• lack of energy, feeling weak or tired
• hair colour changes
• excessive hair loss or thinning
• skin depigmentation
• skin rash with possible skin peeling
• redness and swelling of hands or soles of feet
  Inform your doctor or pharmacist if any of these symptoms become bothersome.

Very common adverse effect that may be detected in blood or urine tests

• increased liver enzyme activity
• decreased blood albumin levels
• protein in urine
• reduced platelet count (blood component responsible for clotting)
• reduced white blood cell count

Common adverse effects (may occur in more than 1 in 10 patients):

• indigestion, bloating, flatulence
• nosebleeds
• dry mouth or mouth ulcers
• infections
• excessive drowsiness
• sleep disturbances
• chest pain, shortness of breath, leg pain and swelling of legs or feet. These may be symptoms of blood clot formation in the body (thrombosis). If a clot detaches, it may travel to the lungs, which may be life-threatening or even fatal.
• reduced ability of the heart to pump blood throughout the body (heart dysfunction)
• slow heartbeat
• bleeding from mouth, rectum, or lungs
• dizziness
• blurred vision
• hot flushes
• swelling of face, hands, legs around ankles, feet, or eyelids due to fluid accumulation
• tingling, weakness, or numbness in hands, arms, legs, or feet
• skin disorders, redness, itching, dry skin
• nail disorders
• burning, stinging, itching, or tingling sensation of the skin
• feeling of cold accompanied by chills
• excessive sweating
• dehydration
• muscle, joint, tendon, or chest pain, muscle cramps
• hoarseness
• shortness of breath
• cough
• coughing up blood
• hiccups
• lung collapse with air trapped between the lung and chest wall, often causing shortness of breath (pneumothorax)
  Inform your doctor or pharmacist if any of these symptoms become bothersome.

Common adverse effects that may be detected in blood or urine tests:

• hypothyroidism
• abnormal liver function
• increased bilirubin levels (a substance produced by the liver)
• increased lipase activity (an enzyme involved in digestion)
• increased creatinine levels (a substance produced by muscles)
• changes in concentration/activity of various other substances/enzymes in blood. Your doctor will inform you about blood test results.

Uncommon adverse effects (may occur in more than 1 in 100 patients):

• stroke
• transient reduction in blood flow to the brain (transient ischaemic attack)
• interruption of blood flow to part of the heart or heart attack (myocardial infarction)
• partial interruption of blood flow to part of the heart (myocardial ischaemia)
• blood clots associated with reduced red blood cells and blood cells involved in clotting (thrombotic microangiopathy). This may damage organs such as the brain and kidneys.
• increased red blood cell count
• sudden shortness of breath, especially if occurring together with acute chest pain and (or) rapid breathing (pulmonary embolism)
• severe gastrointestinal bleeding (from stomach, oesophagus, or intestines), kidneys, vagina, or bleeding into the brain
• heart rhythm disorders (QT interval prolongation)
• perforation of stomach or intestine
• formation of abnormal connections between different parts of the intestine (fistula)
• excessively heavy or irregular menstrual bleeding
• sudden, severe increase in blood pressure (hypertensive crisis)
• pancreatitis
• inflammation, abnormal function, or damage to the liver
• yellowing of skin or whites of eyes (jaundice)
• inflammation of the lining of the abdominal cavity (peritonitis)
• watery nasal discharge
• rashes, which may be itchy or inflammatory (flat or raised spots or blisters)
• frequent bowel movements
• increased skin sensitivity to sunlight
• reduced sensation or sensitivity, especially of the skin
• skin wound that does not heal (skin ulcer)

Rare adverse effects (may occur in more than 1 in 1000 patients):

• lung inflammation
• enlargement and weakening of blood vessel wall or tear in blood vessel wall (aneurysm and arterial dissection)

Frequency not known (frequency cannot be estimated from available data)

• tumour lysis syndrome due to rapid breakdown of tumour cells
• liver failure

Reporting of adverse effects
If any adverse symptoms occur, including any not listed in this leaflet, tell your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions, 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
Adverse effects can also be reported to the marketing authorisation holder. Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Pazopanib TZF

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the bottle and carton following: EXP.
The expiry date refers to the last day of the stated month.
Lot is the batch number.
No special storage conditions apply for this medicine.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Pazopanib TZF contains

• The active substance is pazopanib (as pazopanib hydrochloride). Each coated tablet of Pazopanib TZF 200 mg contains 200 mg of pazopanib. Each coated tablet of Pazopanib TZF 400 mg contains 400 mg of pazopanib.
• The other ingredients of the 200 mg and 400 mg tablets are:
  Tablet core: microcrystalline cellulose, povidone K-30, sodium carboxymethyl starch (type A), magnesium stearate
  Tablet coating: titanium dioxide (E 171), hypromellose (3 mPa·s), hypromellose (6 mPa·s), macrogol,
  polysorbate 80, black iron oxide (E 172) in 200 mg tablets and yellow iron oxide (E 172)
  in 400 mg tablets.

What Pazopanib TZF looks like and contents of the pack
Pazopanib TZF 200 mg coated tablets are grey, capsule-shaped tablets with the imprint "PZ 2" on one side. Tablet dimensions are 14.1 x 5.5 mm.
Pazopanib TZF 400 mg coated tablets are yellow, capsule-shaped tablets with the imprint "PZ 4" on one side. Tablet dimensions are 17.8 x 6.9 mm.
Pack: Bottle containing 30 tablets.

Marketing Authorisation Holder
Tarchomin Pharmaceutical Works "Polfa" Joint Stock Company
A. Fleminga Street 2
03-176 Warsaw, Poland
Tel.: +48 22 811 18 14

Manufacturer
Bluepharma Industria Farmaceutica S.A.
Sao Martinho Do Bispo
3045-016 Coimbra, Portugal

For more detailed information about this medicine, please contact the Marketing Authorisation Holder.