How does it work?

Votrient tablets contain the active ingredient pazopanib, which is a type of medicine known as a protein kinase inhibitor. It works by interfering with the pathways that signal certain cancer cells to grow.

The way that cells in the body work and grow is regulated by various enzymes called protein kinases. These enzymes can be found in certain receptors on the surface of cells that are involved in the growth and spread of cancer cells.

In cancerous cells, the kinases make the cells grow and multiply abnormally. They also stimulate nearby blood vessels to grow into the tumour. The new blood vessels allow the cancer cells to grow and multiply by supplying them with oxygen and nutrients. They also allow the cancerous cells to spread into other areas of the body through the blood circulation.

Pazopanib works by attaching to certain receptors on cancer cells and cells in blood vessel walls and blocking the action of the protein kinases. This stops the signals that tell the cancer cells to grow and multiply. It also stops blood vessels growing into the tumour. This reduces the tumour’s blood supply and with it, its supply of oxygen and nutrients. Both these effects stop the tumour from growing.

Pazopanib is licensed to treat advanced kidney cancer.

What is it used for?

• Advanced kidney cancer (renal cell carcinoma).

Pazopanib may be used as a first-line treatment, or to treat advanced kidney cancer that has not responded to treatment with cytokine therapy such as interleukin or interferon.

Warning!

• Votrient tablets should be taken without food, at least one hour before or two hours after a meal. The tablets must be swallowed whole with water and not broken or crushed.
• You should avoid drinking grapefruit juice while taking this medicine, as it may increase the level of this medicine in your blood and hence increase the risk of side effects
• Your blood pressure should be regularly monitored while you are taking this medicine. If your blood pressure increases you may need to take medicines to reduce it.
• Your heart function should be monitored with an ECG before starting and during treatment with this medicine. Pazopanib can affect the functioning of the heart, especially the heart rhythm. This can develop in to a serious abnormal heart rhythm known as torsades de pointes. In most cases this doesn’t have any symptoms, but some people may experience shortness of breath or an irregular heartbeat if affected. Tell your doctor if you get these symptoms.
• This medicine can sometimes cause liver problems that may very rarely become life-threatening. For this reason, your doctor will want you to have blood tests to check your liver function before you start treatment, at least every four weeks for the first four months of treatment, and then when your doctor feels it necessary. You should tell your doctor if you experience any of the following symptoms while taking this medicine, as they may suggest a problem with your liver: rapidly feeling weak or unwell, unexplained itching, loss of appetite, nausea and vomiting, abdominal pain, yellowing of the skin or whites of the eyes (jaundice), unusually dark urine or bleeding.
• This medicine can cause your thyroid gland to produce less thyroid hormone than normal. Your doctor may want you to have blood tests to check your thyroid function from time to time while you are taking this medicine. Symptoms to look out for include feeling cold, tired or depressed, constipation, weight gain and dry skin.
• This medicine can cause severe bleeding in the digestive system, lungs, kidneys, mouth, vagina or brain. This is uncommon, however, if you experience any signs of bleeding within the body after taking this medicine, for example passing black/tarry/bloodstained stools, vomiting or coughing up blood, blood in the urine, or severe stomach pain; you should stop taking this medicine and consult your doctor immediately.
• This medicine can slow wound healing. For this reason, you will have to stop taking this medicine for at least seven days before going to have any major surgical procedures or operation. You should not start taking it again until your doctor decides any wounds you have are healing well enough.
• This medicine could be harmful to a developing baby. Women who could get pregnant must use a reliable method of contraception to avoid getting pregnant while taking this medicine. Seek further medical advice from your doctor. Tell your doctor immediately if you get pregnant during treatment.

Use with caution in

• People with mild or moderately decreased liver function.
• High blood pressure (hypertension).
• History of heart disease, eg heart failure,heart attack, angina or stroke.
• People with an abnormal heart rhythm, seen on a heart monitoring trace (ECG) as a ‘prolonged QT interval’.
• People with a low level of magnesium in their blood (hypomagnesaemia).
• People with a low level of potassium in their blood (hypokalaemia).
• People taking medicines for an abnormal heart rhythm (antiarrhythmics -see end of factsheet for examples).
• People at increased risk of bleeding due to surgery, injury or disease.
• People taking medicines to prevent blood clots, eg anticoagulants such as warfarin or antiplatelets such as dipyridamole, aspirin or clopidogrel.
• People who have previously had a perforation or fistula in the gut.
• People with an underactive thyroid gland (hypothyroidism).

Not to be used in

• Severely decreased liver function.
• This medicine is not recommended for people with a history of coughing up blood, or bleeding in the brain or gut in the last six months.
• This medicine is not recommended for children and adolescents under 18 years of age, as its safety and effectiveness have not been studied in this age group.
• Breastfeeding.

This medicine should not be used if you are allergic to any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.

If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

• This medicine could be harmful to a developing baby. It should not be used during pregnancy unless considered essential by your doctor, and only if the potential benefit to the mother outweighs any risks to the developing baby. Women who could get pregnant must use a reliable method of contraception to avoid getting pregnant while taking this medicine. Seek further medical advice from your doctor. Tell your doctor immediately if you get pregnant during treatment.
• It is not known if this medicine passes into breast milk. Mothers who need to take this medicine should not breastfeed, because if the medicine does pass into the breast milk it could be harmful to a nursing infant. Seek medical advice from your doctor.

Side effects

Medicines and their possible side effects can affect individualpeople in different ways. The following are some of the side effects that areknown to be associated with this medicine. Just because a side effect is statedhere does not mean that all people using this medicine will experience that orany side effect.

Very common (affect more than 1 in 10 people)

• Decreased appetite.
• Change in taste.
• Increased blood pressure (see warning section above).
• Disturbances of the gut, such as diarrhoea, nausea, vomiting and abdominal pain.
• Fatigue.
• Change in hair colour.
• Alteration of liver enzyme levels.

Common (affect between 1 in 10 and 1 in 100 people)

• Underactive thyroid gland (hypothyroidism – see warning section above).
• Headache.
• Dizziness.
• Pins and needles sensations (paraesthesia).
• Hot flushes.
• Nose bleeds.
• Hoarseness.
• Bloating of the stomach and flatulence.
• Indigestion.
• Loss of hair.
• Skin reactions such as redness, itching, rash, changes in pigmentation, dryness or excessive sweating.
• Fluid retention (oedema).
• Protein in the urine.
• Chest pain.
• Pain or spasms in the muscles.
• Decrease in the number of white blood cells, red blood cells or platelets in the blood.

Uncommon (affect between 1 in 100 and 1 in 1000 people)

• Problems with the heart such as decreased function, heart attack, changes in heart rhythm (see warning section above).
• Stroke or mini stroke.
• Sudden increase in blood pressure (hypertensive crisis).
• Blood clot in the lungs (pulmonary embolism).
• Bleeding, for example from the gut, rectum, vagina, lungs, mouth, throat, urinary tract (see warning section above).
• Inflammation of the pancreas (pancreatitis).
• Bacterial infections in the abdomen (peritonitis).
• Perforation or fistula in the gut.
• Inflammation of the liver (hepatitis), liver failure or jaundice (see warning section above).
• Abnormal reaction of the skin to light, usually a rash (photosensitivity).
• Itchy or inflamed skin rashes.
• Heavy or irregular periods.
• Increased frequency in bowel movement.

The side effects listed above may not include all of the sideeffects reported by the medicine's manufacturer.

For more information about any other possible risks associatedwith this medicine, please read the information provided with the medicine orconsult your doctor or pharmacist.

How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicinesyou are already taking, including those bought without a prescription andherbal medicines, before you start treatment with this medicine. Similarly,check with your doctor or pharmacist before taking any new medicines whiletaking this one, to ensure that thecombination is safe.

The medicines listed below may increase the blood level ofpazopanib, which could increase the risk of its side effects. These medicines should be avoided where possible while you are taking pazopanib:

• the antibiotic medicines clarithromycin and telithromycin
• the antifungal medicines ketoconazole, itraconazole and voriconazole
• the HIV protease inhibitors atazanavir, nelfinavir, ritonavir, saquinavir and indinavir
• lapatinib
• nefazodone.

The medicines listed below may decrease the blood level of pazopanib, which could make it less effective. These medicines should also be avoided where possible while you are taking pazopanib:

• carbamazepine
• phenytoin
• rifampicin
• the herbal remedy St John’s wort (Hypericum perforatum).

There may be an increased risk of bleeding if this medicine isused in combination with the following medicines, which reduce the ability ofthe blood to clot:

• antiplatelet medicines, eg aspirin, clopidogrel, dipyridamole
• anticoagulants, eg warfarin.

There may be an increased chance of an abnormal heart rhythm, seen as a ‘prolonged QT interval’ on an ECG, if this medicine is