Pazopanib accord

Package leaflet: Information for the patient

Pazopanib Accord, 200 mg, film-coated tablets
Pazopanib Accord, 400 mg, film-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.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents:

1. What Pazopanib Accord is and what it is used for
2. Important information 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 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 Accord is used in adult patients for the treatment of:

• 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 Accord

When not to use Pazopanib Accord

• 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 Accord, discuss with the 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 a history of pneumothorax (collapsed lung).
• if the patient has bleeding, blood clots, or arterial narrowing.
• if the patient has stomach or intestinal disorders, such as perforation (a hole) or fistula (abnormal connections between different parts of the intestine).
• if the patient has thyroid disorders.
• if the patient has impaired kidney function.
• if the patient has or has had aneurysm (enlargement and weakening of a blood vessel wall) or dissection of a blood vessel wall.

Inform the doctor if any of these conditions apply. The doctor will decide
whether Pazopanib Accord 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 use of Pazopanib Accord
Pazopanib Accord may cause increased blood pressure. Blood pressure will be monitored
before starting treatment with Pazopanib Accord and during treatment. If the patient develops
high blood pressure, the doctor will prescribe antihypertensive medicines.

• Inform the doctor if the patient has high blood pressure.

If surgery is planned
The doctor will advise stopping treatment with Pazopanib Accord 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 requiring special attention
Pazopanib Accord may worsen certain conditions or cause serious adverse reactions. During
treatment with Pazopanib Accord, it is essential to pay attention to certain symptoms to reduce
the risk of adverse effects. See section 4.
Children and adolescents
Pazopanib Accord is not recommended for patients under 18 years of age. The effect of the
medicine in this patient group has not been established. For safety reasons, the medicine should
not be used in children under 2 years of age.
Pazopanib Accord and other medicines
Tell the doctor or pharmacist about all medicines currently used or recently used, as well as any
medicines the patient plans to take. This also includes herbal preparations and other medicines
available without a prescription.
Some medicines may affect the action of Pazopanib Accord or increase the likelihood of
adverse reactions. Pazopanib Accord 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-receptor antagonists, or antacids) may affect how Pazopanib Accord is absorbed. Advice should be sought from the doctor or nurse.

Tell the doctor or pharmacist if the patient is taking any of these medicines.
Pazopanib Accord with food and drink
Do not take Pazopanib Accord with food, as this affects 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 Accord, do not drink grapefruit juice, as this may increase the risk of adverse reactions.
Pregnancy, breastfeeding, and effects on fertility
Pazopanib Accord is not recommended during pregnancy. It is unknown how Pazopanib
Accord affects pregnancy.

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

Breastfeeding must not be undertaken during treatment with Pazopanib Accord. It is unknown whether the active substances of Pazopanib Accord pass into breast milk. Discuss this with the treating 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 Accord and for at least 2 weeks after the last dose.
Treatment with Pazopanib Accord may affect fertility. Discuss this with the treating doctor.
Driving and operating machinery
Adverse reactions may occur during treatment with Pazopanib Accord that could affect the ability to drive or operate machinery.

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

Pazopanib Accord contains sodium
This 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 Accord

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 800 mg taken once daily. This dose may be taken as two 400 mg tablets or as four 200 mg tablets. 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 Accord with food. The medicine should be taken at least two hours after a meal or one hour before a meal. For example, you may take the medicine two hours after breakfast or one hour before lunch. Pazopanib Accord should be taken at the same time each day.
Tablets should be swallowed whole, one after another, with water. Do not break or crush the tablets, as this affects drug absorption and may increase the risk of adverse effects.
Taking more Pazopanib Accord than prescribed
If you have taken more tablets than recommended, seek advice from your doctor or pharmacist immediately. If possible, show the medicine’s packaging or this leaflet.
If you miss a dose of Pazopanib Accord
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 Accord without your doctor’s advice
Continue taking Pazopanib Accord for as long as your doctor has instructed. Do not discontinue treatment unless advised by your doctor.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.
Possible serious adverse reactions
Brain swelling (reversible posterior leukoencephalopathy syndrome)
Pazopanib Accord may rarely cause brain swelling, which can be life-threatening.
Symptoms include:

• loss of speech
• visual disturbances
• seizures
• disorientation
• high blood pressure

Stop taking Pazopanib Accord 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 Accord 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 Accord. Symptoms of hypertensive crisis may include:

• severe chest pain
• severe headache
• blurred vision
• disorientation
• nausea
• vomiting
• severe restlessness
• shortness of breath
• seizures
• fainting

Stop taking Pazopanib Accord 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. You will be monitored for heart problems during treatment with Pazopanib Accord.
Heart function disorders/heart failure, heart attack
Pazopanib Accord 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 tightness in the chest
• pain in the 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 Accord may affect heart rhythm, which in some people may lead to heart rhythm disorders called torsade de pointes, which can be severe. These may cause very rapid heartbeat, potentially leading to loss of consciousness.
Inform your doctor if you experience changes in heart rhythm, such as heartbeat that is too fast or too slow.
Stroke
Pazopanib Accord 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 Accord 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 very common. Symptoms of bleeding include:

• presence of blood in stool or black-coloured stool
• presence of 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 Accord 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 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 leaks.

Seek immediate medical help if any of these symptoms occur.
Liver problems
Pazopanib Accord may cause liver disorders, which may lead to serious conditions such as liver dysfunction or liver failure, which may be fatal. Your doctor will monitor your liver enzyme activity during treatment with Pazopanib Accord. Symptoms indicating improper 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 Accord may cause blood clots in the veins, especially in the legs (deep vein thrombosis), which may also travel to the lungs (pulmonary embolism). 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 Accord may cause blood clots in small blood vessels in the kidneys and brain, accompanied by a decrease in red blood cells and platelets (thrombotic microangiopathy, TMA). Symptoms include:

• easy bruising
• high blood pressure
• fever
• disorientation
• drowsiness
• seizures
• reduced urine output.

Seek immediate medical help if any of these symptoms occur.
Tumour lysis syndrome
Pazopanib Accord may cause rapid breakdown of tumour cells, leading to tumour lysis syndrome, which may be fatal in some people. Symptoms may include irregular heartbeat, seizures, disorientation, muscle cramps or reduced urine output. Seek immediate medical help if any of these symptoms occur.
Infections
Infections occurring during treatment with Pazopanib Accord 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 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 Accord may rarely cause lung inflammation (interstitial lung disease, pneumonitis), which may be fatal in some patients. Symptoms include shortness of breath or persistent cough. You will be monitored for any lung problems during treatment with Pazopanib Accord.
Seek immediate medical help if any of these symptoms occur.
Thyroid disorders
Pazopanib Accord 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 Accord.
Tell your doctor if you notice significant weight gain or fatigue.
Blurred vision or visual disturbances
Pazopanib Accord may cause detachment or tearing 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 reactions (including possible severe adverse reactions in appropriate frequency categories).
Very common adverse reactions (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 skin peeling
• redness and swelling of the palms or soles of the feet.

Inform your doctor or pharmacist if any of these symptoms become bothersome.
Very common adverse reaction 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 responsible for clotting)
• decreased white blood cell count.

Common adverse reactions (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 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 to the whole body (heart function disorder)
• slow heartbeat
• bleeding from the mouth, rectum or lungs
• dizziness
• blurred vision
• hot flushes
• swelling of the face, hands, legs around the ankles, feet or eyelids due to fluid accumulation
• tingling, weakness or numbness in the 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 with 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 reactions 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 the blood. Your doctor will inform you of the blood test results.

Uncommon adverse reactions (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 accompanied by reduced red blood cells and platelets (thrombotic microangiopathy, TMA). 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 gastrointestinal bleeding (from the stomach, oesophagus or intestines), kidneys, vagina or bleeding into the brain
• heart rhythm disorders (QT interval prolongation)
• perforation of the stomach or intestine
• formation of abnormal connections between different parts of the intestine (fistula)
• abnormally heavy or irregular menstrual bleeding
• sudden, severe increase in blood pressure (hypertensive crisis)
• pancreatitis
• inflammation, abnormal function or damage to the liver
• yellowing of the skin or whites of the eyes (jaundice)
• inflammation of the abdominal lining (peritonitis)
• watery nasal discharge
• rashes, which may be itchy or associated with inflammation (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 adverse reactions (may occur in not more than 1 in 1000 patients):

• lung inflammation
• enlargement and weakening of the blood vessel wall or tearing of the 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 reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 4921301
Fax: +48 22 4921309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
By reporting adverse reactions, more information on the safety of this medicine can be collected.

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 pack, bottle, and carton. The expiry date refers to the last day of the stated month.
No special storage instructions are required for this medicine.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Pazopanib Accord contains
Pazopanib Accord, 200 mg, film-coated tablets

• The active substance 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 (E 460), sodium carboxymethyl starch (type A), povidone (E 1201), magnesium stearate (E 470b).
• Tablet coating (Opadry 13B540026 Pink): hypromellose (E 464), titanium dioxide (E 171), macrogol (E 1521), red iron oxide (E 172), polysorbate 80 (E 433) (see section 2 "Pazopanib Accord contains sodium").

Pazopanib Accord, 400 mg, film-coated tablets

• The active substance 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 (E 460), sodium carboxymethyl starch (type A), povidone (E 1201), magnesium stearate (E 470b).
• Tablet coating (Opadry 13B58802 White): hypromellose (E 464), titanium dioxide (E 171), macrogol (E 1521), polysorbate 80 (E 433) (see section 2 "Pazopanib Accord contains sodium").

What Pazopanib Accord looks like and contents of the pack
Pazopanib Accord, 200 mg, film-coated tablets
Pazopanib Accord, 200 mg are pink, film-coated, capsule-shaped tablets with the number "200" engraved on one side, approximately 14.3 mm × 5.7 mm in size.
Pazopanib Accord, 200 mg, film-coated tablets are packed in cardboard boxes containing 10,
30, 60 or 90 film-coated tablets in transparent PVC/PE/PVDC//Alu blisters,
or
cardboard boxes containing 10×1, 30×1, 60×1 or 90×1 film-coated tablets in transparent
perforated PVC/PE/PVDC//Alu blisters divided into single doses,
or
white HDPE bottles with child-resistant PP caps containing 30 or 90 film-coated tablets,
and collective packs containing 90 film-coated tablets (3 packs of 30 tablets each),
in a cardboard box.

Pazopanib Accord, 400 mg, film-coated tablets
Pazopanib Accord, 400 mg are white, film-coated, capsule-shaped tablets with the number "400" engraved on one side, approximately 18.0 mm × 7.1 mm in size.
Pazopanib Accord, 400 mg, film-coated tablets are packed in cardboard boxes containing 10,
30, 60 or 90 film-coated tablets in transparent PVC/PE/PVDC//Alu blisters,
or
cardboard boxes containing 10×1, 30×1, 60×1 or 90×1 film-coated tablets in transparent
perforated PVC/PE/PVDC/Alu blisters divided into single doses,
or
white HDPE bottles with child-resistant PP caps containing 30 or 60 film-coated tablets,
in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Accord Healthcare Polska Sp. z o.o.
Taśmowa Street 7
02-677 Warsaw
Tel: +48 22 577 28 00

Manufacturer
REMEDICA LTD
Aharnon Street, Limassol Industrial Estate,
3056 Limassol, Cyprus

This medicine is authorised for marketing in the European Economic Area member states under the following names: