Votrient 400 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Votrient 200mg film-coated tablets

Votrient 400mg film-coated tablets

pazopanib

Read the entire leaflet carefully before you start 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Votrient is and what it is used for

Votrient is a type of medicine known as a protein kinase inhibitor. It works by blocking the activity of proteins involved in the growth and spread of cancer cells.

Votrient 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 taking Votrient

Do not take Votrient

• 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

Talk to your doctor before starting Votrient:

• if you have a heart condition.
• if you have a liver condition.
• if you have had heart failure or a heart attack.
• if you have previously had a collapsed lung.
• 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 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 bulge and weakening of the wall of a blood vessel) or a tear in the wall of a blood vessel.

Consult your doctor if you think you may have any of these conditions. Your doctor will decide whether Votrient is suitable for you. You may need additional tests to check that your kidneys, heart, and liver are functioning properly.

High blood pressure and Votrient

Votrient may increase your blood pressure. Your doctor will monitor your blood pressure before and during treatment with Votrient. If you have high blood pressure, you will be given medication to help lower it.

• Tell your doctor if you have high blood pressure.

If you are going to have surgery

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

Conditions requiring your attention

Votrient may worsen other conditions or cause serious side effects. You should be aware of certain symptoms while taking Votrient to reduce the risk of complications. See section 4.

Children and adolescents

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

Other medicines and Votrient

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 medicines obtained without a prescription.

Some medicines may affect how Votrient works or increase the likelihood of side effects. Votrient 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 (e.g., a proton pump inhibitor, H2-receptor antagonist, or antacid) may affect how you should take Votrient. Consult your doctor or nurse for further information.

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

Taking Votrient with food and drinks

Do not take Votrient with food, as food affects the absorption of the medicine. Take it at least 2 hours after a meal or 1 hour before a meal (see section 3).

Do not drink grapefruit juice while being treated with Votrient, as this may increase the likelihood of side effects.

Pregnancy, breastfeeding, and fertility

Votrient is not recommended if you are pregnant. The effect of Votrient during pregnancy is unknown.

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

Do not breastfeed while taking Votrient. It is not known whether Votrient passes into breast milk. Inform your doctor about this.

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

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

Driving and using machines

Votrient 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.

Votrient contains sodium

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

3. How to take Votrient

Follow exactly your doctor's instructions on how to take this medicine. If in doubt, consult your doctor or pharmacist again.

How much to take

The normal 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 Votrient with food. Take it at least two hours after a meal or one hour before a meal. For example, you may take it two hours after breakfast or one hour before lunch. Take Votrient 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 likelihood of adverse effects.

If you take more Votrient than you should

If you take more tablets than you should, seek advice from your doctor or pharmacist immediately. 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 missed doses. Take your next dose at the usual time.

Do not stop treatment with Votrient

Take Votrient for as long as your doctor recommends. Do not stop treatment unless your doctor advises you to do so.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Serious possible adverse effects

Inflammation of the brain (posterior reversible encephalopathy syndrome).

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

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

Stop taking Votrent 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 crisis (sudden and severe increase in blood pressure)

Votrient 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 Votrient. 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 Votrient and seek immediate medical attention if you experience a hypertensive crisis.

Heart problems

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

Cardiac disorder/heart failure, cardiac arrest

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

Signs and symptoms include:

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

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

Changes in heart rhythm (prolongation of QT interval)

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

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

Stroke

Votrient 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 attention if you experience any of these symptoms.

Bleeding

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

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

Perforation and fistula

Votrient may cause a perforation in the stomach or intestinal wall 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 perforation in the stomach or intestine from which foul-smelling or bloody pus is released

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

Liver problems

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

• yellowing of the skin or whites 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

Votrient 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 arms and hands or legs and feet

Thrombotic microangiopathy (TMA)

Votrient may cause blood clots in small blood vessels of the kidneys and brain, accompanied by 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.

Tumour lysis syndrome

Votrient may cause rapid destruction of cancer cells, leading to tumour lysis syndrome, which in some people may be fatal. Symptoms may include irregular heartbeat, seizures, confusion, muscle cramps or spasms, or reduced urine output. Seek immediate medical attention if you experience any of these symptoms.

Infections

Infections that occur while taking Votrient may become severe. 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

Votrient may rarely cause inflammation of the lung (interstitial lung disease, pneumonitis), which in some people may be fatal. Symptoms include difficulty breathing or persistent cough. You will be monitored for any lung problems while taking Votrient.

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

Thyroid problems

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

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

Blurred vision or vision changes

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

Inform your doctor if you notice any changes in vision.

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

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

• high blood pressure
• diarrhoea
• feeling or being sick (nausea or vomiting)
• stomach pain
• loss of appetite
• weight loss
• taste disturbances or loss of taste
• mouth irritation
• headache
• tumour pain
• lack of energy, weakness, or fatigue
• 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:

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

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

• indigestion, bloating, flatulence
• nosebleeds
• dry mouth or mouth ulcers
• infections
• abnormal numbness
• difficulty sleeping
• chest pain, difficulty breathing, leg pain, swelling of 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 may become a health threat or even cause death.
• reduced effectiveness of the heart in pumping blood to the rest of the body (cardiac dysfunction)
• slow heartbeat
• bleeding from mouth, rectum, or lungs
• dizziness
• blurred vision
• hot flushes
• 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, 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 air trapped between the lung 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:

• low thyroid gland activity
• impaired liver function
• increased bilirubin (a substance produced by the liver)
• increased lipase (an enzyme involved in digestion)
• increased creatinine (a substance produced in muscles)
• changes in levels of other chemicals/enzymes in the blood. Your doctor will inform you of the results of 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 may 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)
• serious bleeding in the gastrointestinal tract (in the stomach, esophagus, or intestine), or in the kidneys, vagina, and brain
• changes in heart rhythm (prolongation of 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
• rashes that may itch or become inflamed (flat or raised spots, or blisters)
• frequent bowel movements
• increased skin sensitivity to sunlight
• reduced sensitivity, especially in the skin
• skin wound that does not heal (skin ulcer)

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

• lung inflammation (pneumonitis)
• weakening and bulging of a blood vessel wall or tearing of a 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 effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Votrient

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

Do not use this medicine after the expiry date stated on the bottle and carton following EXP and CAD. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Votrient

• The active substance 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 ingredients in the 200 mg 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 red iron oxide (E172).

Appearance of the product and contents of the pack

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

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

Only certain pack sizes may be marketed.

Marketing Authorization Holder

Novartis Europharm Limited
Vista Building
Elm Park, Merrion Road
Dublin 4
Ireland

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 more information about this medicine, please contact the local representative of the Marketing Authorization Holder:

Belgium/Belgium/Belgium Novartis Pharma N.V. Tel/Tel: +32 2 246 16 11	Lithuania SIA Novartis Baltics Lithuania Branch Tel: +370 5 269 16 50
	Luxembourg/Luxembourg Novartis Pharma N.V. Tel/Tel: +32 2 246 16 11
Czech Republic Novartis s.r.o. Tel: +420 225 775 111	Hungary Novartis Hungária Kft. Tel.: +36 1 457 65 00
Denmark Novartis Healthcare A/S Tlf: +45 39 16 84 00	Malta Novartis Pharma Services Inc. Tel: +356 2122 2872
Germany Novartis Pharma GmbH Tel: +49 911 273 0	Netherlands Novartis Pharma B.V. Tel: +31 88 04 52 555
Estonia SIA Novartis Baltics Estonia Branch Tel: +372 66 30 810	Norway Novartis Norge AS Tlf: +47 23 05 20 00
Greece Novartis (Hellas) S.A.E. Tel: +30 210 281 17 12	Austria Novartis Pharma GmbH Tel: +43 1 86 6570
Spain Novartis Farmacéutica, S.A. Tel: +34 93 306 42 00	Poland Novartis Poland Sp. z o.o. Tel.: +48 22 375 4888
France Novartis Pharma S.A.S. Tél: +33 1 55 47 66 00	Portugal Novartis Farma - Produtos Farmacêuticos, S.A. Tel: +351 21 000 8600
Croatia Novartis Hrvatska d.o.o. Tel. +385 1 6274 220	Romania Novartis Pharma Services Romania SRL Tel: +40 21 31299 01
Ireland Novartis Ireland Limited Tel: +353 1 260 12 55	Slovenia Novartis Pharma Services Inc. Tel: +386 1 300 75 50
Iceland Vistor hf. Sími: +354 535 7000	Slovakia Novartis Slovakia s.r.o. Tel: +421 2 5542 5439
Italy Novartis Farma S.p.A. Tel: +39 02 96 54 1	Finland Novartis Finland Oy Puh/Tel: +358 (0)10 6133 200
Cyprus Novartis Pharma Services Inc. Tel: +357 22 690 690	Sweden Novartis Sverige AB Tel: +46 8 732 32 00
Latvia SIA Novartis Baltics Tel: +371 67 887 070

Date of the most recent review of this leaflet:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu/.