Prospect: information for the user

Votrient 200mg film-coated tablets

Votrient 400mg film-coated tablets

pazopanib

Read this prospect carefully before starting to take this medicine, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section4.

1.What is Votrient and for what it is used

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

3.How to take Votrient

4.Possible adverse effects

5.Storage of Votrient

6.Contents of the package and additional information

Votrient is a type of medication calledprotein kinase inhibitor. It works by preventing the activity of proteins involved in the growth and spread of cancer cells.

Votrient is used in adults for the treatment of:

• advanced or metastatic kidney cancer.

some types of soft tissue sarcoma, which is a type of cancer that affects the body's connective tissue. It can appear in muscles, blood vessels, fat tissue, or other tissues that connect, surround, and protect organs.

Do not take Votrient

• if you are allergicto pazopanib or any of the other ingredients in this medicine (listed in section6).

Consult your doctorif you think you may be allergic.

Warnings and precautions

Consult your doctor before starting Votrient:

• if you have aheart condition.
• ifyou have aliver condition.
• if you have had aheart attack or a cardiac arrest.
• if you have had apulmonary embolismpreviously.
• if you have had problems withbleeding, blood clotting or narrowing of the arteries.
• if you have had problems with yourstomach or intestinessuch asperforation(hole) orfistula(abnormal passages between some parts of the intestines).
• if you havethyroid problems.
• if you have problems with yourkidney function.
• if you have or have had aaneurysm(enlargement and weakening of the wall of a blood vessel) or a tear in the wall of a blood vessel.

Consult your doctorif you think you may have any of these problems. Your doctor will decide if Votrient is suitable for you. You may needadditional teststo check that your kidneys, heart and liver are working properly.

High blood pressure and Votrient

Votrient may increase your blood pressure. Your doctor will check your blood pressure before you start taking Votrient and while you are taking it. If you have high blood pressure, you will be given medication to help lower it.

• Inform your doctorif you have high blood pressure.

If you are to undergo surgery

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

Conditions that require attention

Votrient may make other conditions worse or cause serious side effects. You should be aware of certain symptoms while taking Votrient to reduce the risk of any problems. Seesection4.

Children and adolescents

Votrient is not recommended for people under 18years of age. Its effects in this age group are not yet known. Additionally, it should not be used in children under 2years of age due to safety concerns.

Other medicines and Votrient

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medicine. This includes herbal remedies and over-the-counter medicines.

Some medicines may affect the way Votrient works or increase the risk of side effects. Votrient may also affect the way other medicines work. These include:

• clarithromycin, ketoconazole, itraconazole, rifampicin, telithromycin, voriconazole (used totreat infections).
• atazanavir, indinavir, nelfinavir, ritonavir, saquinavir (used totreat HIV).
• nefazodone (used totreat depression).
• simvastatin and possibly other statins (used totreat high cholesterol).
• medicines thatreduce stomach acidity. The type of medicine you are taking to reduce stomach acidity (for example, a proton pump inhibitor, H2 receptor antagonist or antacid) may affect how you should take Votrient. Consult your doctor or nurse for more information.

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

Taking Votrient with food and drink

Do not take Votrient with food, as this affects the absorption of the medicine. Take it at least two hours after a meal or one hour before a meal (see section3).

Do not drink grapefruit juicewhile taking Votrient, as this may increase the risk of side effects.

Pregnancy, breastfeeding and fertility

Votrient is not recommended if you are pregnant.The effects of Votrient during pregnancy are not yet known.

• Inform your doctorif you are pregnant or planning to become pregnant.
• Use a reliable method of contraceptionwhile taking Votrient, and for at least 2weeks after stopping treatment, to prevent pregnancy.
• If you become pregnant while taking Votrient, inform your doctor.

Do not breastfeed while taking Votrient. The components of Votrient are not yet known to pass into breast milk. Inform your doctor of this.

Male patients(including those who have undergone vasectomy) who have partners who are pregnant or may become pregnant (including those using other methods of contraception) should use condoms during sexual intercourse, while taking Votrient and for at least 2weeks after the last dose.

Fertility may be affectedby treatment with Votrient. Consult your doctor about this.

Driving and operating machinery

Votrient may cause side effects that may affect your ability to drive or operate machinery.

• Avoid driving or operating machinery if you feel dizzy, tired or weak, or if you are lacking energy.

Votrient contains sodium

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

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor or pharmacist again.

How much to take

Usual doseis 800mg taken once a day. The dose can be taken as 2tablets of 400mg or as 4tablets of 200mg. The 800mg once a day dose is the maximum daily dose. Your doctor may need to reduce your dose if you experience side effects.

When to take it

Do not take Votrient 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 a meal. Take Votrient at the same time every day.

Swallow the tablets whole with water, and one after the other. Do not break or crush the tablets as this affects how the medication is absorbed and may increase the risk of side effects.

If you take more Votrient than you should

If you take more tablets than you should,ask your doctor or pharmacist for advice.If possible, show them the packaging or this leaflet.

If you forget to take Votrient

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

Do not stop taking Votrient

Take Votrient for the time recommended by your doctor. Do not stop taking the medication unless your doctor advises you to.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Possible serious side effects

Brain inflammation(posterior reversible encephalopathy syndrome).

In rare cases, Votrient can cause brain inflammation, which can put your life at risk. Among the symptoms are:

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

Stop taking Votrient and seek medical attention immediatelyif 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).

Votrient can cause a sudden and severe increase in blood pressure in some cases. This is known as a hypertensive crisis. Your doctor will monitor your blood pressure while you are taking Votrient. The signs and symptoms of a hypertensive crisis may include:

• severe chest pain
• severe headache
• blurred vision
• confusion
• nausea
• vomiting
• severe anxiety
• difficulty breathing
• seizures
• loss of consciousness

Stop taking Votrient and seek medical attention immediatelyif you experience a hypertensive crisis.

Heart problems

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

Cardiac alteration/heart failure, cardiac arrest

Votrient may affect the way your heart pumps blood or may increase the likelihood of a cardiac arrest.

The signs and symptoms include:

• irregular or rapid heartbeat
• rapid heart palpitations
• loss of consciousness
• chest pain or pressure
• arm, back, neck, or jaw pain
• difficulty breathing
• swelling in the legs

Seek medical attention immediatelyif you experience any of these symptoms.

Changes in heart rhythm (prolongation of the QT interval)

Votrient may affect your heart rhythm, which in some people may trigger a potentially life-threatening heart condition known as torsade de pointes. This can cause an acceleration of your heart rhythm, which may lead to loss of consciousness.

Inform your doctorif you notice anyunusual change in your heartbeat, such as beats that are too fast or too slow.

Stroke

Votrient may increase the likelihood of a stroke. The signs and symptoms of a stroke may include:

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

Seek medical attention immediatelyif you experience any of these symptoms.

Bleeding

Votrient may cause severe bleeding in the digestive tract (in the stomach, esophagus, rectum, or intestines), or in the lungs, kidneys, mouth, vagina, or brain, although this is rare. Among the symptoms are:

• blood in the stool or black stools
• blood in the urine
• abdominal pain
• hemoptysis or vomiting blood

Seek medical attention immediatelyif you experience any of these symptoms.

Perforation and fistula

Votrient may cause a perforation in the stomach or the wall of the intestine or the formation of an abnormal connection between two parts of the digestive tract (a fistula). The signs and symptoms may include:

• severe abdominal pain
• nausea and/or vomiting
• fever
• development of a perforation in the stomach or intestine from which pus or bloody discharge is released

Seek medical attention immediatelyif you experience any of these symptoms.

Liver problems

Votrient may cause liver problems that can become serious conditions such as liver failure or hepatic failure, which can be fatal. Your doctor will monitor your liver enzymes while you are taking Votrient. The signs that your liver may not be functioning correctly may include:

-yellowing of the skin or the white part of the eyes (jaundice)

-dark urine

-fatigue

-nausea

-vomiting

-loss of appetite

-abdominal pain on the right side

-easily bruising

Seek medical attention immediatelyif you experience any of these symptoms.

Clots in the blood

Deep vein thrombosis (DVT) and pulmonary embolism

Votrient may cause clots in the veins, especially in the legs (deep vein thrombosis or DVT), which may travel to the lungs (pulmonary embolism). The signs and symptoms may include:

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

Microangiopathic thrombosis (MAT)

Votrient may cause clots in the blood in small blood vessels in the kidneys and brain, accompanied by a reduction in red blood cells and cells involved in blood clotting (microangiopathic thrombosis, MAT). The signs and symptoms may include:

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

Seek medical attention immediatelyif you experience any of these symptoms.Tumor lysis syndrome

Votrient may cause a rapid destruction of cancer cells, leading to tumor lysis syndrome, which in some people may be fatal. The symptoms may include irregular heartbeat, seizures, confusion, muscle cramps or spasms, or decreased urine output.Seek medical attention immediatelyif you experience any of these symptoms.

Infections

Infections that occur while taking Votrient may become serious. The 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
• urinary tract symptoms
• cuts, scrapes, or wounds that are red, warm, swollen, or painful

Seek medical attention immediatelyif you experience any of these symptoms.

Pneumonia

Votrient may cause, in rare cases, inflammation of the lungs (interstitial lung disease, pneumonitis), which in some people may be fatal. The symptoms include difficulty breathing or a cough that does not go away. Your doctor will monitor you for any lung problems while you are taking Votrient.

Seek medical attention immediatelyif you experience any of these symptoms.

Thyroid problems

Votrient may decrease the amount of thyroid hormone produced in your body. This may cause weight gain and fatigue. Your doctor will monitor your thyroid hormone levels while you are taking Votrient.

Inform your doctorif you notice significant weight gain or fatigue.

Blurred vision or vision changes

Votrient may cause the separation or tearing of the back of the eye (retinal detachment or tear). This may cause blurred vision or vision changes.

Inform your doctorif you notice any change in your vision.

Possible side effects (including possible serious side effects under the category of relevant frequency).

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

• high blood pressure
• diarrhea
• nausea or feeling dizzy
• abdominal 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
• hair color changes
• unusual hair loss or fragility
• unusual skin pigmentation loss
• skin rash, possibly with skin peeling
• redness and inflammation on the palms of the hands and soles of the feet.

Inform your doctor or pharmacistif any of these side effects become problematic.

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

• increased liver enzymes
• decreased albumin in the blood
• protein in the urine
• decreased platelet count (blood cells involved in blood clotting)
• decreased white blood cell count.

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

• indigestion, feeling bloated, flatulence
• nosebleeds
• dry mouth or mouth ulcers
• infections
• numbness
• difficulty sleeping
• chest pain, difficulty breathing, leg pain, inflammation of the legs/feet. These may be signs of blood clotting in the body (thromboembolism). If the clot breaks loose, it may travel to the lungs and become a threat to your health or even fatal.
• heart failure
• slow heart rate
• bleeding from the mouth, rectum, or lungs
• dizziness
• blurred vision
• angina
• swelling caused by fluid retention in the face, hands, ankles, feet, or eyelids
• tingling, weakness, or numbness in the hands, arms, legs, or feet
• skin problems, redness, itching, dry skin
• hair problems
• sensitivity to sunlight
• decreased sensitivity, especially in the skin
• skin wound that does not heal (skin ulcer)

Inform your doctor or pharmacistif any of these side effects become problematic.

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

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

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

• stroke
• temporary reduction in blood supply to the brain (transient ischemic attack)
• heart attack (myocardial infarction)
• partial reduction in blood supply to the heart (myocardial ischemia)
• clots accompanied by a reduction in red blood cells and other cells involved in blood clotting (microangiopathic thrombosis, MAT). These may cause damage to organs such as the brain and kidneys.
• increased red blood cell count
• sudden difficulty breathing, especially when accompanied by severe chest pain and/or rapid breathing (pulmonary embolism)
• severe bleeding in the digestive tract (in the stomach, esophagus, or intestines), or in the kidneys, vagina, or brain
• alterations in heart rhythm (prolongation of the QT interval)
• hole (perforation) in the stomach or intestine
• abnormal connections between parts of the intestine (fistula)
• heavy or irregular menstrual periods
• sudden and severe increase in blood pressure (hypertensive crisis)
• inflammation of the pancreas (pancreatitis)
• inflamed liver, which does not function properly or is damaged
• yellowing of the skin or the white part of the eyes (jaundice)
• inflammation of the abdominal cavity lining (peritonitis)
• runny nose
• skin rash that may itch or inflame (flat or raised patches, or blisters)
• increased bowel movements
• sensitivity to sunlight
• decreased sensitivity, especially in the skin
• skin wound that does not heal (skin ulcer)

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

• inflammation of the lungs(neumonitis)
• increase and weakening of the wall of a blood vessel or tearing of the wall of a blood vessel (aneurysms and arterial dissections)

Unknown frequency(cannot be estimated from available data):

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

Reporting of side effects

If you experienceany type of side effect, consult your doctor or pharmacist, even if it is apossibleside effect that does not appear in this leaflet.You can also report them directly through theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the bottle and on the carton afterEXP andCAD. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Votrient

• The active ingredient is pazopanib (as hydrochloride).

Each Votrient 200 mg film-coated tablet contains 200 mg of pazopanib.

Each Votrient 400 mg film-coated tablet contains 400 mg of pazopanib.

• The other components in the 200 and 400 mg tablets are: hypromellose, macrogol 400, magnesium stearate, microcrystalline cellulose, polysorbate 80, povidone (K30), sodium starch glycolate, titanium dioxide (E171). The 200 mg tablets also contain iron oxide red (E172).

Appearance of the product and contents of the pack

Votrient 200 mg film-coated tablets are capsule-shaped, pink, marked with “GS JT” on one side. They are supplied in bottles of 30 or 90 tablets.

Votrient 400 mg film-coated tablets are capsule-shaped, white, marked with “GS UHL” on one side. They are supplied in bottles of 30 or 60 tablets.

Only some pack sizes may be marketed.

Marketing authorisation holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Responsible manufacturer

Lek Pharmaceuticals d.d.

Verovškova 57

1526 Ljubljana

Slovenia

Novartis Pharmaceutical Manufacturing LLC

Verovškova ulica 57

1000 Ljubljana

Slovenia

Novartis Pharma GmbH

Roonstraße 25

D-90429 Nuremberg

Germany

Glaxo Wellcome, S.A.

Avda.Extremadura, 3

09400 Aranda de Duero, Burgos

Spain

Novartis Farmacéutica S.A.

Gran Via de les Corts Catalanes, 764

08013 Barcelona

Spain

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Germany

For further information about this medicinal product, please consult the representative of the marketing authorisation holder in your country:

Last update of this leaflet:

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agencyhttp://www.ema.europa.eu/.