Pazopanib zentiva: detailed information

Package leaflet: Information for the patient

Pazopanib Zentiva, 200 mg, coated tablets
Pazopanib Zentiva, 400 mg, coated tablets
Pazopanibum
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

Keep this leaflet, as you may need to read it again.
Ask your doctor or pharmacist if you have any questions.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
If you experience any adverse effects, including any possible side effects not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet

What Pazopanib Zentiva is and what it is used for
What you need to know before taking Pazopanib Zentiva
How to take Pazopanib Zentiva
Possible side effects
How to store Pazopanib Zentiva
Contents of the pack and other information

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

Pazopanib Zentiva is a type of medicine known as a protein kinase inhibitor. It works by
inhibiting the activity of proteins involved in the growth and spread of cancer cells.
Pazopanib Zentiva is used in adults to treat:

kidney cancer that is advanced or has spread to other organs.
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 Zentiva

When not to use Pazopanib Zentiva

if the patient is allergic to pazopanib or any of the other ingredients of this medicine (listed in section 6). Consult a doctor if the patient thinks the above applies. Warnings and precautions Before starting treatment with Pazopanib Zentiva, discuss the following with a doctor:
if the patient has heart disease,
if the patient has liver disease,
if the patient has had heart failure or heart attack,
if the patient has had pneumothorax (collapsed lung),
if the patient has experienced bleeding, blood clots, or narrowing of arteries,
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 disorders of kidney function,
if the patient has or has previously had an aneurysm (a weakened and bulging blood vessel wall) or a tear in the wall of a blood vessel. Inform the doctor if any of these conditions apply. The doctor will decide whether Pazopanib Zentiva is suitable for the patient. The patient may need to undergo additional tests to check that the kidneys, heart, and liver are functioning properly.

High blood pressure and treatment with Pazopanib Zentiva
Pazopanib Zentiva may cause high blood pressure. Blood pressure will be monitored before starting and during treatment with Pazopanib Zentiva. If the patient develops high blood pressure, the doctor will prescribe antihypertensive medications. Inform the doctor if the patient has high blood pressure.

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

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

Children and adolescents
Pazopanib Zentiva 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.

Other medicines and Pazopanib Zentiva
Tell the doctor or pharmacist about all medicines currently used, recently used, or planned for use, including herbal preparations and other medicines available without a prescription.

Some medicines may affect the action of Pazopanib Zentiva or increase the likelihood of side effects. Pazopanib Zentiva 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 levels).
medicines that reduce stomach acid secretion. Medicines used to reduce stomach acid secretion (e.g. proton pump inhibitors, H₂-receptor antagonists, or antacids) may affect how Pazopanib Zentiva is absorbed. Consult a doctor or nurse for advice.

Tell the doctor or pharmacist if the patient is taking any of these medicines.

Pazopanib Zentiva with food and drink
Do not take Pazopanib Zentiva with food, as this affects the absorption of the medicine. The medicine should be taken at least 2 hours after a meal or 1 hour before a meal (see section 3).
Do not drink grapefruit juice during treatment with Pazopanib Zentiva, as this may increase the risk of side effects.

Pregnancy, breastfeeding, and fertility

Pazopanib Zentiva is not recommended during pregnancy. It is not known how Pazopanib Zentiva affects pregnancy.

Inform the doctor if the patient is pregnant or planning to become pregnant.
During treatment with Pazopanib Zentiva and for at least 2 weeks after stopping treatment, an effective method of contraception must be used to prevent pregnancy.
Inform the doctor if the patient becomes pregnant while taking Pazopanib Zentiva.

Breastfeeding is not recommended while taking Pazopanib Zentiva. It is not known whether the components of Pazopanib Zentiva pass into breast milk. Discuss this with the treating doctor.

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

Treatment with Pazopanib Zentiva may affect fertility. Discuss this with the treating doctor.

Driving and operating machinery
Side effects may occur during treatment with Pazopanib Zentiva that could affect the ability to drive or operate machinery.

Avoid driving or operating machinery if the patient experiences dizziness, fatigue, weakness, or low energy levels.

Pazopanib Zentiva 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 Zentiva

This medicine should always be taken exactly as prescribed by the doctor. If in doubt,
consult the doctor or pharmacist.
How many tablets to take
Pazopanib Zentiva, 200 mg, coated tablets:
The usual dose of Pazopanib Zentiva 200 mg is four tablets (800 mg of pazopanib)
taken once daily. This is the maximum daily dose. The doctor may recommend reducing
the dose if the patient experiences adverse reactions.
Pazopanib Zentiva, 400 mg, coated tablets:
The usual dose of Pazopanib Zentiva 400 mg is two tablets (800 mg of pazopanib)
taken once daily. This is the maximum daily dose. The doctor may recommend reducing
the dose if the patient experiences adverse reactions.
When to take the medicine
Do not take Pazopanib Zentiva with food. The medicine should be taken at least
two hours after a meal or one hour before a meal.
For example, the medicine may be taken two hours after breakfast or one hour before lunch.
Pazopanib Zentiva should be taken at the same time each day.
The 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 reactions.
Taking more than the recommended dose of Pazopanib Zentiva
If the patient takes too many tablets, seek advice from a doctor or pharmacist immediately.
If possible, show the medicine packaging or this leaflet.
If a dose of Pazopanib Zentiva is missed
Do not take a double dose to make up for the missed dose. Take the next dose at the usual time.
Do not stop taking Pazopanib Zentiva without medical advice
Pazopanib Zentiva should be taken for as long as prescribed by the doctor. Do not stop
taking the medicine unless instructed by the doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Possible serious side effects
Brain swelling (reversible posterior leukoencephalopathy syndrome)
Pazopanib Zentiva may in rare cases cause brain swelling, which may be life-threatening. Symptoms include:

loss of speech
vision disturbances
seizures
confusion
high blood pressure Stop taking Pazopanib Zentiva 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 Zentiva may occasionally cause a sudden and severe rise in blood pressure. This condition is known as a hypertensive crisis. Your doctor will monitor your blood pressure while you are taking Pazopanib Zentiva. Symptoms of a hypertensive crisis may include:

severe chest pain
severe headache
blurred vision
confusion
nausea
vomiting
severe restlessness
shortness of breath
seizures
fainting Stop taking Pazopanib Zentiva 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 Zentiva, you will be monitored for heart problems. Heart dysfunction/heart failure, heart attack Pazopanib Zentiva may affect the heart's ability to pump blood or may increase the risk of heart attack. Signs and symptoms may 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 legs Seek immediate medical help if any of these symptoms occur. Changes in heart rhythm (QT prolongation) Pazopanib Zentiva may affect heart rhythm, which in some people may lead to a serious heart rhythm disorder called torsade de pointes. This may cause a very fast heartbeat, possibly leading to loss of consciousness. Inform your doctor if you experience unusual changes in heart rhythm, such as a heartbeat that is too fast or too slow.

Stroke
Pazopanib Zentiva may increase the risk of 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 any of these symptoms occur. Bleeding Pazopanib Zentiva may cause severe bleeding from the gastrointestinal tract (from the stomach, oesophagus, rectum or intestines), or from the lungs, kidneys, mouth, vagina, or bleeding into the brain, although this is not very common. Symptoms of bleeding include:
blood in the stool or black stools
blood in the urine
abdominal pain
coughing up blood or vomiting blood Seek immediate medical help if any of these symptoms occur.

Perforation and fistula
Pazopanib Zentiva 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). Signs and symptoms of this condition 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 drains Seek immediate medical help if any of these symptoms occur.

Liver problems
Pazopanib Zentiva may cause liver problems, which may lead to serious conditions such as impaired liver function and liver failure, which may result in death. Your doctor will monitor your liver enzyme activity during treatment with Pazopanib Zentiva. Signs indicating impaired liver function may include:

yellowing of the skin or whites of the eyes (jaundice)
dark 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 (DVT) and pulmonary embolism
Pazopanib Zentiva may cause blood clots in the veins, especially in the legs (deep vein thrombosis), which may travel to the lungs (pulmonary embolism). Signs and symptoms of this condition may include:

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

Thrombotic microangiopathy (TMA)
Pazopanib Zentiva 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, TMA). Signs and symptoms include:

easy bruising
high blood pressure
fever
confusion
drowsiness
seizures
reduced urine output Seek immediate medical help if any of these symptoms occur.

Tumour lysis syndrome
Pazopanib Zentiva 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, confusion, muscle cramps or twitching, or reduced urine output. Seek immediate medical help if any of these symptoms occur.
Infections
Infections occurring during treatment with Pazopanib Zentiva 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 and (or) wheezing
pain when passing urine
cuts, scratches or wounds that are red, warm, swollen or painful Seek immediate medical help if any of these symptoms occur.

Lung inflammation
Pazopanib Zentiva may in rare cases cause lung inflammation (interstitial lung disease, pneumonia), which may be fatal in some patients. Symptoms include: shortness of breath or cough that does not go away. While taking Pazopanib Zentiva, you will be monitored for any lung problems. Seek immediate medical help if any of these symptoms occur.
Thyroid disorders
Pazopanib Zentiva may reduce the production of thyroid hormones in the body. This may lead to weight gain and fatigue. Your doctor will monitor thyroid hormone levels during treatment with Pazopanib Zentiva.
Tell your doctor if you notice significant weight gain or fatigue.

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

Possible side effects (including possible severe side effects in appropriate frequency categories).
Very common side 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
changes in hair colour
excessive hair loss or thinning
skin discolouration
skin rash with possible peeling
redness and swelling of hands or soles of feet Inform your doctor or pharmacist if any of these symptoms become bothersome.

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

increased liver enzyme activity
decreased blood albumin levels
protein in the urine
decreased platelet count (blood component enabling clot formation)
decreased white blood cell count

Common side effects (may occur in not more than 1 in 10 patients):

indigestion, bloating, flatulence
nosebleeds
dry mouth or mouth ulcers
infections
excessive sleepiness
sleep disturbances
chest pain, shortness of breath, leg pain and swelling of legs or feet. These may be signs of blood clots forming 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 to the whole 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
haemoptysis
hiccups
lung collapse with air trapped between lung and chest wall, often causing shortness of breath (pneumothorax) Inform your doctor or pharmacist if any of these symptoms become bothersome.

Common side 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 in muscles)
changes in levels/activity of various other substances/enzymes in blood. Your doctor will inform you about blood test results.

Uncommon side effects (may occur in not 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 platelets (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 sudden chest pain and (or) rapid breathing (pulmonary embolism)
severe bleeding from gastrointestinal tract (from stomach, oesophagus or intestines), kidneys, vagina or bleeding into the brain
heart rhythm disorders (QT prolongation)
perforation (tearing) 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 sensitivity of the skin to sunlight
reduced sensation or sensitivity, especially of the skin
skin wound that does not heal (skin ulcer)

Rare side effects (may occur in not more than 1 in 1000 patients):

pneumonia
enlargement and weakening of blood vessel wall or tearing of 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 side effects If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Side effects can be reported directly to the Department of Monitoring 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 Side effects can also be reported to the marketing authorisation holder. Reporting side effects helps provide more information on the safety of the medicine.

5. How to store Pazopanib Zentiva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date (EXP) stated on the bottle or
blister pack and cardboard box. The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Medicines must 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 Zentiva contains
Pazopanib Zentiva, 200 mg, film-coated tablets:

The active substance is pazopanib (as pazopanib hydrochloride). Each film-coated tablet contains 200 mg of pazopanib.
The other ingredients are:
Tablet core: microcrystalline cellulose, sodium carboxymethyl starch (type A), povidone, magnesium stearate.
Tablet coating: hypromellose, titanium dioxide (E 171), polyethylene glycol 400, iron oxide red (E 172), polysorbate 80.

Pazopanib Zentiva, 400 mg, film-coated tablets:

The active substance is pazopanib (as pazopanib hydrochloride). Each film-coated tablet contains 400 mg of pazopanib.
The other ingredients are:
Tablet core: microcrystalline cellulose, sodium carboxymethyl starch (type A), povidone, magnesium stearate.
Tablet coating: hypromellose, titanium dioxide (E 171), polyethylene glycol 400, polysorbate 80.

What Pazopanib Zentiva looks like and contents of the pack
Pazopanib Zentiva, 200 mg, film-coated tablets:
Pazopanib Zentiva, 200 mg, film-coated tablets are capsule-shaped, pink, marked "200" on one side, approximately 14 mm x 6 mm in size.
They are available in bottles with child-resistant closure: 30, 90 tablets, and bulk pack of 90 (3 packs of 30) film-coated tablets in a cardboard box.
They are available in transparent PVC/PE/PVDC/Aluminium blisters: 30, 90 tablets, and bulk pack of 90 (3 packs of 30) film-coated tablets in a cardboard box.
They are available in transparent single-dose PVC/PE/PVDC/Aluminium blisters: 30 x 1, 90 x 1, and bulk pack of 90 x 1 (3 packs of 30 x 1) film-coated tablets in a cardboard box.

Pazopanib Zentiva, 400 mg, film-coated tablets:
Pazopanib Zentiva, 400 mg, film-coated tablets are capsule-shaped, white, marked "400" on one side, approximately 18 mm x 7 mm in size.
They are available in bottles with child-resistant closure: 30, 60 film-coated tablets in a cardboard box.
They are available in transparent PVC/PE/PVDC/Aluminium blisters: 30, 60, 90 tablets, and bulk pack of 60 (2 packs of 30) film-coated tablets in a cardboard box.
They are available in transparent single-dose PVC/PE/PVDC/Aluminium blisters: 30 x 1, 60 x 1, 90 x 1, and bulk pack of 60 x 1 (2 packs of 30 x 1) film-coated tablets in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Zentiva, k.s.
U kabelovny 130
Dolní Měcholupy
102 37 Prague 10
Czech Republic

Manufacturer
Remedica Ltd.
Aharnon Street, Limassol Industrial Estate,
3056 Limassol
Cyprus
PharOS MT Ltd.
HF62X, Hal Far Industrial Estate,
Birzebbugia
BBG3000
Malta

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Denmark, Estonia, Finland, Norway, Poland, Czech Republic, Sweden, Italy: Pazopanib Zentiva
Bulgaria: Пазопаниб Зентива 200mg филмирани таблетки
Пазопаниб Зентива 400mg филмирани таблетки
Croatia: Pazopanib Zentiva 200 mg filmom obložene tablete
Pazopanib Zentiva 400 mg filmom obložene tablete
France: Pazopanib Zentiva 200 mg comprimé pelliculé
Pazopanib Zentiva 400 mg comprimé pelliculé
Spain: Pazopanib Zentiva 200 mg comprimidos recubiertos con película EFG
Pazopanib Zentiva 400 mg comprimidos recubiertos con película EFG
Lithuania: Pazopanib Zentiva 200 mg plėvele dengtos tabletės
Pazopanib Zentiva 400 mg plėvele dengtos tabletės
Latvia: Pazopanib Zentiva 200 mg apvalkotās tabletes
Pazopanib Zentiva 400 mg apvalkotās tabletes
Germany: Pazopanib Zentiva 200 mg filmtabletten
Pazopanib Zentiva 400 mg filmtabletten
Slovakia: Pazopanib Zentiva 200 mg
Pazopanib Zentiva 400 mg
Romania: PAZOPANIB ZENTIVA 200 mg comprimate filmate
PAZOPANIB ZENTIVA 400 mg comprimate filmate
Hungary: Pazopanib Zentiva 200mg filmtabletta
Pazopanib Zentiva 400mg filmtabletta

For more detailed information, please contact the local representative of the Marketing Authorisation Holder:
Zentiva Polska Sp. z o.o.,
ul. Bonifraterska 17
00-203 Warsaw, Poland
Tel.: +48 22 375 92 00