Pazopanib Accord

Patient Information Leaflet

Pazopanib Accord 200 mg film-coated tablets, 400 mg film-coated tablets

pazopanib
Generic medicine
Please read this entire 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, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

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

Pazopanib Accord 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 Accord 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 the organs.

2. What you should know before taking Pazopanib Accord

Do not take Pazopanib Accord

• 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 Accord:

• 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 lung collapse.
• 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 kidney function problems.
• if you have or have had an aneurysm (dilation and weakening of a blood vessel wall) or a tear in the wall of a blood vessel. Inform your doctor if any of these apply to you. Your doctor will decide whether Pazopanib Accord 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 Accord
Pazopanib Accord can increase blood pressure. Your blood pressure will be monitored
before starting and during treatment with Pazopanib Accord. 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 about to undergo surgery
Your doctor will stop Pazopanib Accord at least 7 days before surgery, as the medicine may affect wound healing. Treatment will be restarted once the wound has healed adequately.
Conditions to which you should pay attention
Pazopanib Accord may worsen certain conditions or cause serious side effects. To reduce
the risk of any problems, you should be aware of certain symptoms while taking
Pazopanib Accord. See section 4.
Children and adolescents
Pazopanib Accord 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 Accord
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 Accord works and may increase the likelihood
of side effects. Conversely, Pazopanib Accord 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 should take Pazopanib Accord. Consult your doctor or nurse for advice. Inform your doctor or pharmacist if you are taking any of these medicines.

Pazopanib Accord with food and drinks
Do not take Pazopanib Accord 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 Accord, as this may increase the risk of side effects.
Pregnancy and breastfeeding
Pazopanib Accord is not recommended if you are pregnant. The effect of Pazopanib Accord during pregnancy is unknown.

• Inform your doctor if you are pregnant or planning to become pregnant.
• Use a reliable method of contraception while taking Pazopanib Accord and for at least 2 weeks after stopping it to prevent pregnancy.
• If you become pregnant during treatment with Pazopanib Accord, inform your doctor immediately.

You must not breastfeed while taking Pazopanib Accord. It is not known whether the components of Pazopanib Accord 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 could become pregnant (including those using other contraceptive methods), you must use a condom during sexual intercourse while taking Pazopanib Accord and for at least 2 weeks after the last dose.
Fertility may be affected by treatment with Pazopanib Accord. Discuss this with your doctor.
Driving and using machines
Pazopanib Accord may cause side effects that could affect your ability to drive or operate machinery.

• Avoid driving or operating machinery if you feel dizzy, tired, weak, or have low energy levels.

Pazopanib Accord 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 Accord

Take this medicine exactly as your doctor has told you. If you are unsure,
consult your doctor or pharmacist.
How much to take
The recommended dose is 800 mg once daily. The dose can be taken as
2 tablets of 400 mg or as 4 tablets of 200 mg. The 800 mg once-daily dose is the
maximum daily dose. Your doctor may need to reduce the dose if you experience
unwanted effects.
When to take it
Do not take Pazopanib Accord 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
Accord 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 unwanted effects.
If you take more Pazopanib Accord 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 Accord
Do not take a double dose to make up for the missed dose. Take only the next dose at the usual time.
Do not stop Pazopanib Accord without medical advice
Take Pazopanib Accord for as long as your doctor recommends. Do not stop unless your doctor tells you to do so.

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 Accord 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 Accord and seek immediate medical help if you experience any of these symptoms, or if you have a headache together with any of these symptoms.

Hypertensive crisis (sudden and severe increase in blood pressure)
Pazopanib Accord 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 Accord. 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 Accord 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 Accord.

Heart dysfunction/heart failure, heart attack
Pazopanib Accord may affect the heart's pumping activity or increase the likelihood of having a heart attack. Signs and symptoms include:

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

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

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

Stroke
Pazopanib Accord 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 Accord may cause serious bleeding in the digestive 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 urine
• stomach pain
• coughing up or vomiting blood

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

Perforation and fistula
Pazopanib Accord may cause a tear (perforation) in the wall of 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 Accord 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 liver enzymes while you are taking Pazopanib Accord. 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 Accord may cause blood clots 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 Accord may cause blood clots in small blood vessels in the kidneys and brain, accompanied by a decrease in red blood cells and platelets involved in blood clotting (thrombotic microangiopathy, TMA). 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 Accord 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 occurring while taking Pazopanib Accord may become severe. Symptoms of infections may include:

• fever
• flu-like symptoms such as cough, fatigue and body aches that do not go away
• shortness of breath and/or breathlessness
• 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 Accord 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 Accord, you will be monitored for lung problems.
Seek immediate medical help if you experience any of these symptoms.

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

Blurred or impaired vision
Pazopanib Accord 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, according to the relevant frequency category)

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

• high blood pressure
• diarrhoea
• feeling unwell (nausea or vomiting)
• stomach pain
• loss of appetite
• weight loss
• taste disturbances 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 worsen or 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 platelet count in the blood (cells that help blood to clot)
• reduced white blood cell count 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 and this may be life-threatening or even fatal.
• reduced heart pumping efficiency (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 disorders
• skin sensations of burning, stinging, itching or tingling
• 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 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 red blood cell count in the blood
• sudden onset of shortness of breath, especially when accompanied by severe chest pain and/or rapid breathing (pulmonary embolism)
• serious bleeding from the digestive tract (such as stomach, oesophagus or intestine), or from kidneys, vagina or brain
• heart rhythm disturbances (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 rise in blood pressure (hypertensive crisis)
• inflammation of the pancreas (pancreatitis)
• inflamed liver that is not functioning properly or is damaged
• yellowing of the skin or whites of the eyes (jaundice)
• inflammation of the abdominal lining (peritonitis)
• runny nose
• skin rash which may be itchy or inflamed (flat or raised spots or blisters)
• frequent bowel movements
• increased sensitivity of the skin to sunlight
• reduced sensation, especially in 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)

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

• tumour lysis syndrome due to 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
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Pazopanib Accord

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date (Exp.) stated on the blister, bottle, and outer box.
The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines 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 Accord contains
Pazopanib Accord 200 mg film-coated tablets

• The active substance in Pazopanib Accord is pazopanib (as hydrochloride). Each film-coated tablet contains pazopanib hydrochloride equivalent to 200 mg of pazopanib.
• The other components are: Tablet core: microcrystalline cellulose (E460), sodium carboxymethyl starch (type A), povidone (E1201), magnesium stearate (E470b). Tablet coating (Opadry pink 13B540026): hypromellose (E464), titanium dioxide (E171), macrogol (E1521), red iron oxide (E172), polysorbate 80 (E433). (See section 2 “Pazopanib Accord contains sodium”).

Pazopanib Accord 400 mg film-coated tablets

• The active substance in Pazopanib Accord is pazopanib (as hydrochloride). Each film-coated tablet contains pazopanib hydrochloride equivalent to 400 mg of pazopanib.
• The other components are: Tablet core: microcrystalline cellulose (E460), sodium carboxymethyl starch (type A), povidone (E1201), magnesium stearate (E470b). Tablet coating (Opadry white 13B58802): hypromellose (E464), titanium dioxide (E171), macrogol (E1521), polysorbate 80 (E433). (See section 2 “Pazopanib Accord contains sodium”).

Description of the appearance of Pazopanib Accord and package contents
Pazopanib Accord 200 mg film-coated tablets
The Pazopanib Accord 200 mg film-coated tablets are capsule-shaped, pink, with “200” printed on one side, approximately 14.3 × 5.7 mm in size.
Pazopanib Accord is packaged in boxes containing 10, 30, 60 or 90 film-coated tablets in transparent PVC/PE/PVDC/Alu blisters,
or
boxes containing 10×1, 30×1, 60×1 or 90×1 film-coated tablets in transparent, perforated, unit-dose divisible blisters made of PVC/PE/PVDC/Alu,
or
white HDPE bottles with child-resistant polypropylene caps containing 30 or 90 film-coated tablets, and multiple packs containing 90 film-coated tablets (3 packs of 30) in a box.

Pazopanib Accord 400 mg film-coated tablets
The Pazopanib Accord 400 mg film-coated tablets are capsule-shaped, white, with “400” printed on one side, approximately 18.0 × 7.1 mm in size.
Pazopanib Accord is packaged in boxes containing 10, 30, 60 or 90 film-coated tablets in transparent PVC/PE/PVDC/Alu blisters,
or
boxes containing 10×1, 30×1, 60×1 or 90×1 film-coated tablets in transparent, perforated, unit-dose divisible blisters made of PVC/PE/PVDC/Alu,
or
white HDPE bottles with child-resistant polypropylene caps containing 30 or 60 film-coated tablets in a box.

Not all pack sizes may be marketed.

Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center,
Moll de Barcelona,
s/n, Edifici Est 6ª planta,
08039 Barcelona,
Spain

Manufacturer
Remedica Ltd
Aharnon Street, Limassol Industrial Estate,
Limassol 3056, Cyprus
PharOS MT Ltd.
HF62X, Hal Far Industrial Estate,
Birzebbugia BBG 3000, Malta

This medicinal product is authorised in the European Economic Area Member States under the following names:

Member State Proposed brand name
Hungary Pazopanib Accord 200/400 mg filmtabletta
Bulgaria Pazopanib Accord 200/400 mg филмирани таблетки
Czech Republic Pazopanib Accord
Croatia Pazopanib Accord 200/400 mg filmom obložene tablete
Poland Pazopanib Accord
Romania Pazopanib Accord 200/400 mg comprimate filmate
Slovenia Pazopanib Accord 200/400 mg filmsko obložene tablete
Slovakia Pazopanib Accord 200/400 mg filmom obalené tablety
Spain Pazopanib Accord 200/400 mg comprimidos recubiertos con película
Italy Pazopanib Accord
Portugal Pazopanib Accord 200/400 mg comprimidos revestidos por película
Greece Pazopanib Accord 200/400 mg επικαλυμμένα με λεπτό υμένιο δισκία

Member State Proposed brand name
France PAZOPANIB ACCORD 200 mg, comprimé pelliculé
PAZOPANIB ACCORD 400 mg, comprimé pelliculé
Belgium Pazopanib Accord 200/400 mg Filmtabletten
Denmark Pazopanib Accord 200/400 mg filmovertrukne tabletter
Estonia Pazopanib Accord
Finland Pazopanib Accord 200/400 mg tabletti, kalvopäällysteinen
Lithuania Pazopanib Accord 200/400 mg plėvele dengtos tabletės
Latvia Pazopanib Accord 200/400 mg apvalkotās tabletes
Netherlands Pazopanib Accord 200/400 mg filmomhulde tabletten
Norway Pazopanib Accord
Sweden Pazopanib Accord 200/400 mg filmdragerade tabletter
Ireland Pazopanib Accord 200/400 mg film-coated tablets