Pazopanib EG

Patient Information Leaflet: Information for the patient

PAZOPANIB EG 200 mg film-coated tablets, 400 mg film-coated tablets

Generic medicine
Please read this leaflet carefully before 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, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What PAZOPANIB EG is and what it is used for

PAZOPANIB EG is a type of medicine called a protein kinase inhibitor. It works by blocking
the activity of proteins involved in the growth and spread of cancer cells.
PAZOPANIB EG is used in adults to treat:

• advanced kidney cancer or cancer that has spread to other organs.
• certain types of soft tissue sarcoma, which is a type of tumour affecting the body's supportive tissues. It may occur in muscles, blood vessels, fatty tissue, or other tissues that support, surround, and protect organs.

2. What you should know before taking PAZOPANIB EG

Do not take PAZOPANIB EG

• if you are allergic to pazopanib or to any of the other ingredients of this medicine (listed in section 6). Check with your doctor if you think this applies to you.

Warnings and precautions
Talk to your doctor before taking PAZOPANIB EG:

• if you have a heart disease.
• if you have a liver disease.
• if you have previously had heart failure or a heart attack.
• if you have previously had a collapse of the lung.
• if you have had problems related to bleeding, blood clots, or narrowing of the arteries.
• if you have had stomach or intestinal problems, such as a perforation (hole) or a fistula (abnormal passage forming between parts of the intestine).
• if you have thyroid problems.
• if you have problems with your kidneys.
• if you have or have had an aneurysm (a bulge and weakening in the wall of a blood vessel) or a tear in the wall of a blood vessel. Inform your doctor if any of these apply to you. Your doctor will determine whether PAZOPANIB EG is suitable for you. You may need additional tests to check that your kidneys, heart, and liver are functioning properly.

High blood pressure and PAZOPANIB EG
PAZOPANIB EG can increase blood pressure. Your blood pressure will be monitored before starting and during treatment with PAZOPANIB EG. If you have high blood pressure, you will be treated with medicines to lower it.

• Inform your doctor if you have high blood pressure.

If you are scheduled for surgery
Your doctor will stop PAZOPANIB EG at least 7 days before surgery because the medicine may affect wound healing. Treatment will be restarted once the wound has healed adequately.

Conditions to watch for
PAZOPANIB EG may worsen certain pre-existing conditions or cause serious side effects. You should be aware of certain symptoms while taking PAZOPANIB EG to minimize any risks. See section 4.

Children and adolescents
PAZOPANIB EG is not recommended for people under 18 years of age. It is not yet known how it works in this age group. Furthermore, it must not be used in children under 2 years of age due to safety concerns.

Other medicines and PAZOPANIB EG
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes herbal medicines and other medicines you can buy without a prescription.

Some medicines can affect how PAZOPANIB EG works and may increase the risk of side effects. Conversely, PAZOPANIB EG may affect how other medicines work. These include:

• clarithromycin, ketoconazole, itraconazole, rifampicin, telithromycin, voriconazole (used to treat infections).
• atazanavir, indinavir, nelfinavir, ritonavir, saquinavir (used to treat HIV).
• nefazodone (used to treat depression).
• simvastatin and possibly other statins (used to treat high cholesterol levels).
• medicines that reduce stomach acidity. The type of medicine you are taking to reduce stomach acidity (e.g. proton pump inhibitors, H2 antagonists, or antacids) may affect how you take PAZOPANIB EG. Consult your doctor or nurse for advice.

Inform your doctor or pharmacist if you are taking any of these medicines.

PAZOPANIB EG with food and drinks
Do not take PAZOPANIB EG with food, as this affects how the medicine is absorbed. Take it at least two hours after a meal or one hour before a meal (see section 3).
Do not drink grapefruit juice while being treated with PAZOPANIB EG, as this may increase the risk of side effects.

Pregnancy, breastfeeding, and fertility
PAZOPANIB EG is not recommended if you are pregnant. The effect of PAZOPANIB EG during pregnancy is unknown.

• Tell your doctor if you are pregnant or if you are planning to become pregnant.
• Use a reliable method of contraception while taking PAZOPANIB EG and for at least 2 weeks after stopping the treatment to prevent pregnancy.
• If you become pregnant while being treated with PAZOPANIB EG, inform your doctor.

You must not breastfeed while taking PAZOPANIB EG. It is not known whether the components of PAZOPANIB EG pass into breast milk. Discuss this with your doctor.

If you are a male patient (even if you have had a vasectomy) and have a partner who is pregnant or who could become pregnant (including those using other contraceptive methods), you must use a condom during sexual intercourse while taking PAZOPANIB EG and for at least 2 weeks after the last dose.

Fertility may be affected by treatment with PAZOPANIB EG. Discuss this with your doctor.

Driving and using machines
PAZOPANIB EG may cause side effects that could affect your ability to drive or operate machinery.

• Avoid driving or operating machinery if you feel confused, tired, weak, or if your energy levels are low.

PAZOPANIB EG contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per film-coated tablet, i.e., essentially ‘sodium-free’.

3. How to take PAZOPANIB EG

Take this medicine exactly as your doctor has told you. If you have any doubts, consult your
doctor or pharmacist.
How much medicine to take
PAZOPANIB EG 200 mg film-coated tablets:
The usual dose is four 200 mg PAZOPANIB EG tablets (800 mg of pazopanib) taken once daily. This is the maximum daily dose. Your doctor may need to reduce the dose if you experience side effects.
PAZOPANIB EG 400 mg film-coated tablets:
The usual dose is two 400 mg PAZOPANIB EG tablets (800 mg of pazopanib) taken once daily. This is the maximum daily dose. Your doctor may need to reduce the dose if you experience side effects.
When to take it
Do not take PAZOPANIB EG with food. Take it at least two hours after a meal or one hour before a meal.
For example, you could take it two hours after breakfast or one hour before lunch. Take PAZOPANIB EG every day at approximately the same time.
Swallow the tablets whole with water, one after the other. Do not break or crush the tablets, as this affects how the medicine is absorbed and may increase the risk of side effects.
If you take more PAZOPANIB EG than you should
If you take too many tablets, contact your doctor or pharmacist for advice. If possible, show them the pack or this leaflet.
If you forget to take PAZOPANIB EG
Do not take a double dose to make up for the forgotten dose. Take only the next dose at the usual time.
Do not stop PAZOPANIB EG without medical advice
Take PAZOPANIB EG for as long as your doctor recommends. Do not stop treatment unless instructed by your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious possible side effects

Brain swelling (reversible posterior leukoencephalopathy syndrome)
PAZOPANIB EG may rarely cause brain swelling, which can be life-threatening. Symptoms include:

• loss of speech
• changes in vision
• seizures (epileptic fits)
• confusion
• high blood pressure

Stop taking PAZOPANIB EG and seek immediate medical help if you experience any of these symptoms, or if you have a headache accompanied by any of these symptoms.

Hypertensive crisis (sudden and severe increase in blood pressure)
PAZOPANIB EG may occasionally cause a sudden and severe rise in blood pressure. This is known as a hypertensive crisis. Your doctor will monitor your blood pressure while you are taking PAZOPANIB EG. Signs and symptoms of a hypertensive crisis may include:

• severe chest pain
• severe headache
• blurred vision
• confusion
• nausea
• vomiting
• severe anxiety
• shortness of breath
• seizures (epileptic fits)
• fainting

Stop taking PAZOPANIB EG and seek immediate medical help if you develop a hypertensive crisis.

Heart problems
The risk of these problems may be higher in people who already have heart disease or who are taking other medicines. You will be monitored for heart problems while taking PAZOPANIB EG.

Heart dysfunction/heart failure, heart attack
PAZOPANIB EG may affect the pumping action of the heart or increase the likelihood of a heart attack. Signs and symptoms include:

• irregular or fast heartbeat
• rapid heartbeat
• fainting
• chest pain or pressure
• pain in arms, back, neck or jaw
• shortness of breath
• swollen legs

Seek immediate medical help if you experience any of these symptoms.

Changes in heart rhythm (QT prolongation)
PAZOPANIB EG may affect the heart rhythm, which in some people may lead to a potentially serious heart condition known as torsades de pointes. This may cause a very rapid heartbeat leading to sudden loss of consciousness.
Inform your doctor if you notice any unusual changes in your heartbeat, such as a heartbeat that is too fast or too slow.

Stroke
PAZOPANIB EG may increase the likelihood of having a stroke. Signs and symptoms of stroke may include:

• numbness or weakness on one side of the body
• difficulty speaking
• headache
• dizziness

Seek immediate medical help if you experience any of these symptoms.

Bleeding
PAZOPANIB EG may cause severe bleeding in the gastrointestinal tract (such as stomach, oesophagus, rectum or intestine), or in the lungs, kidneys, mouth, vagina and brain, although this is not common. Symptoms include:

• passing blood in stools or black stools
• blood in the urine
• stomach pain
• coughing or vomiting blood

Seek immediate medical help if you experience any of these symptoms.

Perforation and fistula
PAZOPANIB EG may cause a tear (perforation) in the stomach or intestine, or the development of an abnormal connection between two parts of the digestive tract (a fistula). Signs and symptoms may include:

• severe stomach pain
• nausea and/or vomiting
• fever
• development of a hole (perforation) in the stomach or intestine, from which foul-smelling, bloody pus is released

Seek immediate medical help if you experience any of these symptoms.

Liver problems
PAZOPANIB EG may cause liver problems that can lead to serious conditions such as liver dysfunction and liver failure, which may be fatal. Your doctor will monitor your liver enzymes while you are taking PAZOPANIB EG. Signs that the liver may not be working properly may include:

• yellowing of the skin or whites of the eyes (jaundice)
• dark urine
• fatigue
• nausea
• vomiting
• loss of appetite
• pain in the right side of the stomach (abdomen)
• easy bruising

Seek immediate medical help if you experience any of these symptoms.

Blood clots

Deep vein thrombosis (DVT) and pulmonary embolism
PAZOPANIB EG may cause blood clots to form in the veins, especially in the legs (deep vein thrombosis or DVT), which may travel to the lungs (pulmonary embolism). Signs and symptoms may include:

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

Thrombotic microangiopathy (TMA)
PAZOPANIB EG may cause blood clots to form in small blood vessels in the kidneys and brain, accompanied by a decrease in red blood cells and platelets (thrombotic microangiopathy, TMA). This may damage organs such as the brain and kidneys. Signs and symptoms may include:

• easy bruising
• high blood pressure
• fever
• confusion
• drowsiness
• seizures (epileptic fits)
• reduced urine output

Seek immediate medical help if you experience any of these symptoms.

Tumour lysis syndrome
PAZOPANIB EG may cause rapid breakdown of tumour cells, leading to tumour lysis syndrome, which in some people may be fatal. Symptoms may include irregular heartbeat, seizures (fits), confusion, muscle cramps or spasms, or reduced urine output.
Seek immediate medical help if you experience any of these symptoms.

Infections
Infections that occur while taking PAZOPANIB EG may become severe. Symptoms of infection may include:

• fever
• flu-like symptoms such as cough, fatigue and body aches that do not go away
• shortness of breath, wheezing, nosebleeds
• pain when urinating
• cuts, scratches or wounds that are red, warm, swollen or painful

Seek immediate medical help if you experience any of these symptoms.

Lung inflammation
Rarely, PAZOPANIB EG may cause inflammation of the lungs (interstitial lung disease, pneumonia), which in some people may be fatal. Symptoms include shortness of breath or persistent cough. While taking PAZOPANIB EG, you will be monitored for lung problems.
Seek immediate medical help if you experience any of these symptoms.

Thyroid problems
PAZOPANIB EG may reduce the amount of thyroid hormone produced by the body. This may cause weight gain and fatigue. While taking PAZOPANIB EG, your thyroid hormone levels will be monitored.
Inform your doctor if you notice significant weight gain or fatigue.

Blurred or impaired vision
PAZOPANIB EG may cause separation or tearing of the inner layer at the back of the eye (retinal detachment or tear). This may lead to blurred or impaired vision.
Inform your doctor if you notice any changes in your vision.

Possible side effects (including potentially serious side effects by relevant frequency category)

Very common side effects (may affect more than 1 in 10 people):

• high blood pressure
• diarrhoea
• feeling unwell or nausea (nausea or vomiting)
• stomach pain
• loss of appetite
• weight loss
• taste disturbance or loss of taste
• mouth pain
• headache
• tumour site pain
• lack of energy, feeling weak or tired
• change in hair colour
• unusual hair loss or thinning
• loss of skin pigment
• skin rash, possibly with skin peeling
• redness and swelling of the palms of the hands or soles of the feet

Inform your doctor or pharmacist if any of these side effects become bothersome.

Very common side effects that may be detected by blood or urine tests:

• increased liver enzymes
• reduced albumin in the blood
• protein in the urine
• reduced number of platelets in the blood (cells that help blood to clot)
• reduced number of white blood cells in the blood

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

• indigestion, bloating, flatulence
• nosebleeds
• dry mouth or mouth ulcers
• infections
• unusual drowsiness
• difficulty sleeping
• chest pain, shortness of breath, leg pain, and swelling of legs/feet. These may be signs of a blood clot in the body (thromboembolism). If the clot breaks loose, it may travel to the lungs, which can be life-threatening or even fatal.
• reduced effectiveness of the heart in pumping blood around the body (cardiac dysfunction)
• slow heartbeat
• bleeding from mouth, rectum or lung
• dizziness
• blurred vision
• hot flushes
• swelling of face, hands, ankles, feet or eyelids due to fluid retention
• tingling, weakness or numbness in hands, arms, legs or feet
• skin disorders, redness, itching, dry skin
• nail changes
• burning, prickling, itching or tingling sensation on the skin
• feeling cold with chills
• excessive sweating
• dehydration
• muscle, joint, tendon or chest pain, muscle spasms
• hoarseness
• shortness of breath
• cough
• coughing up blood
• hiccups
• collapsed lung with trapped air between the lung and chest wall, often causing shortness of breath (pneumothorax)

Inform your doctor or pharmacist if any of these side effects become bothersome.

Common side effects that may be detected by blood or urine tests:

• reduced thyroid gland activity
• liver function abnormalities, increased bilirubin (a substance produced by the liver)
• increased lipase (an enzyme involved in digestion)
• increased creatinine (a substance produced by muscles)
• changes in blood levels of various other chemicals/enzymes. Your doctor will inform you of the blood test results.

Uncommon side effects (may affect up to 1 in 100 people):

• stroke
• temporary interruption of blood supply to the brain (transient ischaemic attack)
• interruption of blood supply to part of the heart or heart attack (myocardial infarction)
• partial interruption of blood supply to part of the heart (myocardial ischaemia)
• blood clots accompanied by a decrease in red blood cells and clotting cells (thrombotic microangiopathy, TMA). These may damage organs such as the brain and kidneys
• increased number of red blood cells in the blood
• sudden onset of shortness of breath, especially when accompanied by severe chest pain and/or rapid breathing (pulmonary embolism)
• severe gastrointestinal bleeding (such as in stomach, oesophagus or intestine), or in kidneys, vagina and brain
• heart rhythm disorders (QT prolongation)
• hole (perforation) in the stomach or intestine
• abnormal passage forming between parts of the intestine (fistula)
• heavy or irregular menstrual periods
• sudden sharp increase in blood pressure (hypertensive crisis)
• inflammation of the pancreas (pancreatitis)
• inflamed liver that is not working properly or damaged
• yellowing of the skin or whites of the eyes (jaundice)
• inflammation of the lining of the abdominal cavity (peritonitis)
• runny nose
• skin rash that may be itchy or inflamed (flat or raised spots or blisters)
• frequent bowel movements
• increased sensitivity of the skin to sunlight
• reduced sensitivity, especially of the skin
• skin wound that does not heal (skin ulcer)

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

• lung inflammation (pneumonia)
• dilation and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and arterial dissections)

Not known (frequency cannot be estimated from the available data)

• tumour lysis syndrome resulting from rapid breakdown of tumour cells
• liver failure

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 at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store PAZOPANIB EG

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial or blister pack and carton
after the words “Expiry .” The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of any medicine 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 PAZOPANIB EG contains
PAZOPANIB EG 200 mg film-coated tablets:

• The active substance is pazopanib (as hydrochloride). Each film-coated tablet contains 200 mg of pazopanib.
• Other components are: Tablet core: microcrystalline cellulose (E460), sodium starch glycolate (type A), povidone K30 (E1201), magnesium stearate (E470b). Tablet coating: hypromellose (E464), titanium dioxide (E171), macrogol 400 (E1521), iron oxide red (E172), polysorbate 80 (E433).

PAZOPANIB EG 400 mg film-coated tablets:

• The active substance is pazopanib (as hydrochloride). Each film-coated tablet contains 400 mg of pazopanib.
• Other components are: Tablet core: microcrystalline cellulose (E460), sodium starch glycolate (type A), povidone K30 (E1201), magnesium stearate (E470b). Tablet coating: hypromellose (E464), titanium dioxide (E171), macrogol 400 (E1521), polysorbate 80 (E433).

Description of the appearance of PAZOPANIB EG and contents of the pack
PAZOPANIB EG 200 mg film-coated tablets:
PAZOPANIB EG 200 mg film-coated tablets are capsule-shaped, pink tablets, with "200" printed on one side, approximately 14.3 mm x 5.7 mm in size.
Supplied in clear/transparent aluminium-PVC/PE/PVDC blisters containing 30, 90 tablets, multiple packs of 90 (3 packs of 30 tablets).
Also supplied in perforated, divisible unit-dose blisters made of clear/transparent aluminium-PVC/PE/PVDC, containing 30 x 1, 90 x 1 tablets, multiple pack of 90 x 1 (3 packs of 30 x 1 tablets).

PAZOPANIB EG 400 mg film-coated tablets:
PAZOPANIB EG 400 mg film-coated tablets are capsule-shaped, white tablets, with "400" printed on one side, approximately 18.0 mm x 7.1 mm in size.
Supplied in clear/transparent aluminium-PVC/PE/PVDC blisters containing 30, 60 tablets, multiple packs of 60 (2 packs of 30 tablets).
Also supplied in perforated, divisible unit-dose blisters made of clear/transparent aluminium-PVC/PE/PVDC, containing 30 x 1, 60 x 1 tablets, multiple pack of 60 x 1 (2 packs of 30 x 1 tablets).
Not all pack sizes may be marketed.

Marketing Authorisation Holder
EG S.p.A., Via Pavia 6, 20136 Milano, Italy

Manufacturer
Remedica Ltd
Aharnon Street, Limassol Industrial Estate
Limassol 3056, Cyprus
PharOS MT Ltd
HF62X, Hal Far Industrial Estate
Birzebbugia BBG3000, Malta
STADA Arzneimittel AG
Stadastrasse 2 – 18
61118 Bad Vilbel, Germany

This medicinal product is authorised in the European Economic Area (EEA) Member States under the following names:
HU Pazopanib Stada Arzneimittel 200 mg filmtabletta
Pazopanib Stada Arzneimittel 400 mg filmtabletta
DE Pazopanib AL 200 mg Filmtabletten
Pazopanib AL 400 mg Filmtabletten
IT Pazopanib EG