Pazopanib Accord 200 mg film-coated tablets EFG

Patient Information Leaflet

Introduction

Patient Information Leaflet

Pazopanib Accord 200 mg film-coated tablets EFG

Pazopanib Accord 400 mg film-coated tablets EFG

Read the entire leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this leaflet, as 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, and you should not give it to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse effects, talk to your doctor or pharmacist, even if the adverse effects are not listed in this leaflet. See section 4.

Package leaflet contents

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 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 is used in adults for the treatment of:

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

2. What you need to know before starting to take 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).

Consult your doctor if you think this may apply to you.

Warnings and precautions

Consult your doctor before starting to take Pazopanib Accord:

• if you have a heart condition.
• if you have a liver disease.
• if you have had heart failure or a heart attack.
• if you have had a lung collapse previously.
• if you have had problems with bleeding, blood clotting, or narrowing of the arteries.
• if you have had stomach or intestinal problems such as perforation (a hole) or fistula

(abnormal passages that form between certain parts of the intestine).

• if you have thyroid problems.
• if you have problems with kidney function.
• if you have or have had an aneurysm (a bulging and weakening of the wall of a blood vessel) or a tear in the wall of a blood vessel.

Talk to your doctor if you think you may have any of these conditions. Your doctor will decide whether pazopanib 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 can increase your blood pressure. Your doctor will check your blood pressure before you start taking pazopanib and during treatment. If you have high blood pressure, you will receive treatment with medications to help lower it.

• Inform your doctor if you have high blood pressure.

If you are going to undergo surgery

Your doctor will tell you to stop taking pazopanib at least 7 days before your surgery, as this may affect wound healing. Your treatment will be resumed once the wounds have healed properly.

Conditions that require your attention

Pazopanib may worsen other conditions or cause serious adverse effects. You should be aware of certain symptoms while taking pazopanib to reduce the risk of any problems. See section 4.

Children and adolescents

Pazopanib is not recommended for use in individuals under 18 years of age. Its efficacy in this age group has not yet been established. Moreover, 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 need to take any other medicines. This includes herbal medicines and over-the-counter medications.

Some medicines may affect how pazopanib works or increase the likelihood that you experience side effects. Pazopanib may also 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 for the treatment of high cholesterol levels).
• medicines that reduce stomach acid. The type of medicine you are taking to reduce stomach acid (for example, a proton pump inhibitor, H2-receptor antagonist, or antacid) may affect how you should take Pazopanib.

Speak to your doctor or nurse for further information.

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

Taking Pazopanib Accord with food and beverages

Do not take pazopanib with food, as food affects the absorption of the medicine. 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, as this may increase the likelihood of adverse effects.

Pregnancy, breastfeeding, and fertility

Pazopanib is not recommended if you are pregnant. The effect of pazopanib 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, and for at least 2 weeks after stopping treatment, to prevent pregnancy.
• If you become pregnant during treatment with pazopanib, inform your doctor immediately.

Do not breastfeed while taking pazopanib. It is not known whether pazopanib components pass into breast milk. Inform your doctor about this.

Male patients (including those who have had a vasectomy) who have partners who are pregnant or who could become pregnant (including those using other contraceptive methods) must use condoms during sexual intercourse while taking pazopanib and for at least 2 weeks after the last dose.

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

Driving and operating machines

Pazopanib may cause adverse effects that could affect your ability to drive or operate machinery.

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

Pazopanib accord contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per film-coated tablet; this is, essentially, "sodium-free".

3. How to take Pazopanib Accord

Follow exactly the instructions for using this medicine as given by your doctor. If in doubt, consult your doctor or pharmacist again.

How much to take

The usual dose is 800 mg taken 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 your dose if you experience adverse effects.

When to take it

Do not take pazopanib with food. Take it at least two hours after a meal or one hour before a meal. For example, you can take it two hours after breakfast or one hour before lunch. Take pazopanib at the same time each day.

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 adverse effects.

If you take more Aazopanib Accord than you should

If you take more tablets than you should, seek advice from your doctor or pharmacist. If possible, show them the pack or this leaflet.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number: 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to take Pazopanib Accord

Do not take a double dose to make up for missed doses. Take your next dose at the usual time.

Do not interrupt treatment with Pazopanib Accord

Take pazopanib for as long as your doctor has recommended. Do not stop treatment unless your doctor advises you to do so.

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone will experience them.

Serious potential side effects

Brain inflammation (posterior reversible encephalopathy syndrome).

Pazopanib may rarely cause inflammation of the brain, which can be life-threatening. Symptoms include:

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

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

Hypertensive crises (sudden and severe increase in blood pressure)

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

• severe chest pain
• severe headache
• blurred vision
• confusion
• nausea
• vomiting
• severe anxiety
• difficulty breathing
• seizures
• fainting

Stop taking pazopanib and seek immediate medical attention if you experience a hypertensive crisis.

Heart problems

The risk of these problems may be higher in people who have a heart condition or who are taking other medicines. While you are taking pazopanib, your doctor will monitor you for any heart-related problems.

Cardiac dysfunction/heart failure, cardiac arrest

Pazopanib may affect the way the heart pumps or may increase the likelihood of cardiac arrest.

Signs and symptoms include:

• irregular or rapid heartbeat
• fast heart palpitations
• fainting
• chest pain or pressure
• pain in the arms, back, neck, or jaw
• difficulty breathing
• swelling in the legs

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

Changes in heart rhythm (QT interval prolongation)

Pazopanib may affect heart rhythm, which in some people may trigger a potentially serious heart condition known as torsade de pointes. This can cause a rapid heartbeat that may lead to loss of consciousness.

Tell your doctor if you notice any unusual changes in your heartbeat, such as beats that are too fast or too slow.

Stroke

Pazopanib may increase the risk 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 attention if you experience any of these symptoms.

Bleeding

Pazopanib may cause serious bleeding in the gastrointestinal tract (in the stomach, esophagus, rectum, or intestine), or in the lungs, kidneys, mouth, vagina, and brain, although this is uncommon. Symptoms include:

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

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

Perforation and Fistula

Pazopanib may cause a perforation in the stomach or intestinal wall, or the development of an abnormal connection between two parts of the gastrointestinal tract (a fistula). Signs and symptoms may include:

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

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

Liver Problems

Pazopanib can cause liver problems that may become serious conditions such as liver failure, which can be fatal. Your doctor will monitor your liver enzymes while you are taking pazopanib. Signs that your liver may not be functioning properly include:

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

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

Blood clots

Deep vein thrombosis (DVT) and pulmonary embolism

Pazopanib 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:

• sharp chest pain
• difficulty breathing
• rapid breathing
• leg pain
• swelling of the arms and hands or legs and feet

Thrombotic microangiopathy (TMA)

Pazopanib may cause blood clots in the small blood vessels of the kidneys and brain, along with a reduction in red blood cells and platelets (thrombotic microangiopathy, TMA). Signs and symptoms may include:

• easy bruising
• high blood pressure
• fever
• confusion
• drowsiness
• seizures
• decreased urine output

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

Tumor lysis syndrome

Pazopanib may cause rapid destruction of cancer cells, leading to tumor lysis syndrome, which can be fatal in some people. Symptoms may include irregular heartbeat, seizures, confusion, muscle cramps or spasms, or decreased urination. Seek immediate medical attention if you experience any of these symptoms.

Infections

Infections that occur while you are taking pazopanib can become serious. Symptoms of infections may include:

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

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

Lung inflammation

Pazopanib may, in rare cases, cause lung inflammation (interstitial lung disease, pneumonitis), which in some people may be fatal. Symptoms include shortness of breath or cough that does not go away. Your doctor will monitor you for any lung problems while you are taking pazopanib.

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

Thyroid problems

Pazopanib may decrease the amount of thyroid hormone produced in your body. This can cause weight gain and fatigue. Your thyroid hormone levels will be monitored while you are taking pazopanib.

Tell your doctor if you notice significant weight gain or fatigue.

Blurred or altered vision

Pazopanib may cause separation or tearing of the back of the eye (retinal detachment or tear). This can lead to blurred or altered vision.

Tell your doctor if you notice any changes in your vision

Possible adverse effects (including potentially serious adverse effects under the relevant frequency category).

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

• high blood pressure
• diarrhea
• feeling or being sick (nausea or vomiting)
• stomach pain
• loss of appetite
• weight loss
• changes in taste or loss of taste
• mouth irritation
• headache
• tumor pain
• lack of energy, feeling weak or tired
• changes in hair color
• unusual hair loss or hair fragility
• loss of skin pigmentation
• skin rash, possibly with skin peeling
• redness and inflammation of the palms of the hands and soles of the feet.

Inform your doctor or pharmacist if any of these adverse effects become troublesome.

Very common adverse effects that may appear in your blood or urine tests:

• increase in liver enzymes
• decrease in blood albumin
• protein in the urine
• decrease in platelet count (blood cells involved in blood clotting)
• decrease in white blood cell count

Frequent adverse effects (may affect up to 1 in 10 people):

• indigestion, feeling bloated, flatulence
• nosebleeds
• dry mouth or mouth ulcers
• infections
• abnormal numbness
• difficulty sleeping
• chest pain, shortness of breath, leg pain, swelling of legs/feet. These may be signs of blood clotting in the body (thromboembolism). If the clot dislodges, it may travel to the lungs and may become life-threatening or even cause death.
• reduced heart ability to pump blood to the rest of the body (cardiac dysfunction)
• slow heartbeats
• bleeding from mouth, rectum, or lungs
• dizziness
• blurred vision
• hot flashes
• swelling due to fluid retention in the face, hands, ankles, feet, or eyelids
• tingling, weakness, or numbness in hands, arms, legs, or feet
• skin disorders, redness, itching, dry skin
• nail disorders
• burning, itching, pruritus, or tingling sensation on the skin
• feeling cold, with chills
• excessive sweating
• dehydration
• muscle, joint, tendon, or chest pain, muscle spasms
• hoarseness
• difficulty breathing
• cough
• coughing up blood
• hiccups
• collapsed lung with trapped air in the space between the lungs and chest wall, often causing difficulty breathing (pneumothorax).

Inform your doctor or pharmacist if any of these adverse effects become troublesome.

Common adverse effects that may appear in your blood or urine tests:

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

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

• stroke
• temporary reduction in 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 other cells involved in blood clotting (thrombotic microangiopathy, TMA). These can cause organ damage, such as in the brain and kidneys.
• increased number of red blood cells
• sudden difficulty breathing, especially when accompanied by sharp chest pain and/or rapid breathing (pulmonary embolism)
• severe bleeding in the gastrointestinal tract (in the stomach, oesophagus, or intestine), or in the kidneys, vagina, or brain
• disturbances in heart rhythm (prolongation of the QT interval)
• hole (perforation) in the stomach or intestine
• abnormal passages forming between parts of the intestine (fistula)
• heavy or irregular menstrual periods
• sudden increases in blood pressure (hypertensive crisis)
• inflammation of the pancreas (pancreatitis)
• inflamed, poorly functioning, or damaged liver
• yellowing of the skin or whites of the eyes (jaundice)
• inflammation of the lining of the abdominal cavity (peritonitis)
• runny nose
• skin rashes that may itch or become 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 adverse effects (may affect up to 1 in 1,000 people):

• inflammation of the lung (pneumonitis)
• enlargement and weakening of the wall of a blood vessel or tear in the blood vessel wall (aneurysms and arterial dissections)

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

• tumour lysis syndrome, resulting from rapid destruction of cancer cells
• liver failure

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor, pharmacist, or nurse, even if it is a possible adverse reaction not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. Storage of Pazopanib Accord

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the packaging after EXP or CAD. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines must not be disposed of via wastewater drains or household waste. Dispose of unused medicines and their containers at the SIGRE Point at your pharmacy. If you are unsure, ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Pazopanib Accord

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 (E460), Sodium carboxymethyl starch (type A) (from potato), Povidone (E1201), Magnesium stearate (E470b)

Film coating (Opadry Pink 13B540026): Hypromellose (E464), Titanium dioxide (E171), Macrogol (E1521), Iron oxide red (E172), Polysorbate 80 (E433) (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 (E460), Sodium carboxymethyl starch (type A) (from potato), Povidone (E1201), Magnesium stearate (E470b)

Film coating (Opadry White 13B58802): Hypromellose (E464), Titanium dioxide (E171), Macrogol (E1521), Polysorbate 80 (E433) (see section 2 “Pazopanib Accord contains sodium”).

Appearance of the Product and Contents of the Container

Pazopanib Accord 200 mg film-coated tablets

Pazopanib Accord 200 mg are capsule-shaped, pink film-coated tablets marked with "200" on one side, with approximate dimensions of 14.3 mm x 5.7 mm.

Pazopanib Accord 200 mg is packaged in boxes containing 10, 30, 60 or 90 film-coated tablets in transparent PVC/PE/PVDC//Alu blisters,

or

in boxes containing 10x1, 30x1, 60x1 or 90x1 film-coated tablets in perforated single-dose blisters of transparent PVC/PE/PVDC//Alu.

or

in white HDPE bottles with white PP child-resistant caps containing 30 or 90 film-coated tablets, and multiple pack containing 90 (3 packs of 30) film-coated tablets in a box.

Pazopanib Accord 400 mg film-coated tablets

Pazopanib Accord 400 mg are capsule-shaped, white film-coated tablets marked with "400" on one side, with approximate dimensions of 18.0 mm x 7.1 mm.

Pazopanib Accord 400 mg is packaged in boxes containing 10, 30, 60 or 90 film-coated tablets in transparent PVC/PE/PVDC//Alu blisters.

or

in boxes containing 10x1, 30x1, 60x1 or 90x1 film-coated tablets in perforated single-dose blisters of transparent PVC/PE/PVDC//Alu.

or

in white HDPE bottles with white PP child-resistant caps containing 30 or 60 film-coated tablets in a box.

Only certain pack sizes may be marketed.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6th floor

08039 Barcelona

Spain

Manufacturer

Remedica Ltd
Aharnon Street, Limassol Industrial Estate,
Limassol 3056, Cyprus

or

PharOS MT Ltd.
HF62X, Hal Far Industrial Estate,
Birzebbugia BBG3000, Malta

This medicinal product is authorized in the European Economic Area member states under the following names

Member State	Medicinal Product Name
Hungary	Pazopanib Accord 200/400 mg film-coated tablets
Bulgaria	Pazopanib Accord 200/400 mg ????????? ????????
Czech Republic	Pazopanib Accord
Croatia	Pazopanib Accord 200/400 mg film-coated tablets
Poland	Pazopanib Accord
Romania	Pazopanib Accord 200/400 mg film-coated tablets
Slovenia	Pazopanib Accord 200/400 mg film-coated tablets
Slovakia	Pazopanib Accord 200/400 mg film-coated tablets
Spain	Pazopanib Accord 200/400 mg film-coated tablets
Italy	Pazopanib Accord
Portugal	Pazopanib Accord 200/400 mg film-coated tablets
Greece	Pazopanib Accord 200/400 mg επικαλυμμ?να με λεπτ? υμ?νιο δισκ?α
France	PAZOPANIB ACCORD 200 mg, film-coated tablet PAZOPANIB ACCORD 400 mg, film-coated tablet
Belgium	Pazopanib Accord 200/400 mg film-coated tablets
Denmark	Pazopanib Accord 200/400 mg film-coated tablets
Estonia	Pazopanib Accord
Finland	Pazopanib Accord 200/400 mg film-coated tablet
Lithuania	Pazopanib Accord 200/400 mg film-coated tablets
Latvia	Pazopanib Accord 200/400 mg film-coated tablets
Netherlands	Pazopanib Accord 200/400 mg film-coated tablets
Norway	Pazopanib Accord
Sweden	Pazopanib Accord 200/400 mg film-coated tablets
Ireland	Pazopanib Accord 200/400 mg film-coated tablets

Date of the most recent review of this leaflet: October 2023

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.