How does it work?

Afinitor tablets contain the active ingredient everolimus, 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.

Everolimus works by attaching to a certain protein inside the cancer cells and blocking the action of a protein kinase called mammalian target of rapamycin (mTOR). 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.

Everolimus is licensed to treat advanced kidney cancer.

Everolimus tablets should be taken once daily at the same time each day and consistently with or without food. This helps to maintain effective levels of the medicine in your blood.

What is it used for?

• Advanced kidney cancer (renal cell carcinoma).

Everolimus is licensed to treat advanced kidney cancer that has not responded to treatment with other medicines called VEGF-targeted therapy, for example sunitinib or sorafenib.

Warning!

• Afinitor tablets should be swallowed whole with water and not crushed or chewed. They can be taken with or without food, but you must keep to the same routine of taking the tablets either with or without food at the same time each day.
• 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.
• This medicine can increase your risk of infections. You should tell your doctor immediately if you get any signs of infection whilst taking this medicine, for example, a high temperature (fever), sore throat, mouth ulcers or swollen glands.
• Mouth ulcers and inflammation of the lining of the mouth are common side effects experienced by people taking this medicine. It is important to speak to your doctor before treating any mouth ulcers. Mouthwashes with alcohol or peroxide should be avoided.
• This medicine can decrease the number of blood cells in your blood. A low white blood cell count can increase your susceptibility to infections; a low red blood cell count causes anaemia and a low platelet count can cause problems with blood clotting and increase the risk of bleeding. For this reason, you will need regular blood tests to monitor your blood cells during treatment with this medicine. Tell your doctor immediately if you experience any of the following symptoms during your treatment, as they may indicate problems with your blood cells: unexplained bruising or bleeding, purple spots, sore mouth or throat, mouth ulcers, high temperature (fever) or other signs of infection, or suddenly feeling tired, breathless, or generally unwell.
• You should also have regular blood tests to monitor your liver and kidney function and your blood sugar and cholesterol levels while you are having treatment with this medicine.
• This medicine can slow wound healing. For this reason, you may need to stop taking this medicine before any major surgical procedures or operation. Follow your doctor’s instructions.
• 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.
• The ability of men to father a child may be affected by treatment with this medicine. It is important to discuss fertility with your doctor before starting treatment.

Use with caution in

• People with liver disease.
• Diabetes.
• People with increased blood cholesterol levels.
• People who have recently had surgery.
• People with an infection (infections should normally be treated before this medicine is started).
• History of hepatitis B infection.

Not to be used in

• Severely decreased liver function.
• Pregnancy.
• Breastfeeding.
• Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption (Afinitor tablets contain lactose).
• 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.

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. Women who could get pregnant must use a reliable method of contraception to avoid getting pregnant whilst taking this medicine. Seek further medical advice from your doctor.
• 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 individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here, it does not mean that all people using this medicine will experience that or any side effect.

Very common (affect more than 1 in 10 people)

• Infections.
• Inflammation of the lining of the mouth (stomatitis) or mouth ulcers (see warning section above).
• Increased levels of triglycerides in the blood (hypertriglyceridaemia).
• Increased levels of cholesterol in the blood.
• Increased blood glucose levels (hyperglycemia).
• Low blood phosphate levels (hypophosphataemia).
• Decrease in the number of white blood cells, haemoglobin or platelets in the blood.
• Feeling weak or fatigued.
• Disturbances of the gut such as diarrhoea, nausea or vomiting.
• Nose bleeds.
• Change in taste.
• Loss of appetite.
• Inflammation of the lungs (pneumonitis - see warning section above).
• Cough.
• Difficulty breathing (dyspnoea).
• Skin reactions such as dry skin, itching or rash.
• Swollen ankles due to fluid retention.

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

• Dehydration.
• Difficulty sleeping (insomnia).
• Inflammation of the lining of the eye (conjunctivitis).
• Swelling of the eyelids.
• Increased blood pressure (hypertension).
• Headache.
• Dry mouth.
• Difficulty or pain when swallowing (dysphagia).
• Indigestion.
• Painful redness, swelling, blistering or ulceration of the palms and soles (hand-foot syndrome or palmar-plantar erythrodysesthesia).
• Skin redness, peeling or inflammation.
• Chest pain.
• Fever.
• Weight loss.
• Coughing up blood.

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

• Heart failure.
• Swelling of the lips, throat and tongue (angioedema).
• Slowed wound healing.
• Diabetes.

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

For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult 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 are strong inhibitors of the enzyme in the liver that breaks down everolimus. They may increase the blood level of everolimus, which could increase the risk of its side effects. These are not recommended for people taking everolimus:

• the antibiotic medicines clarithromycin and telithromycin
• the antifungal medicines ketoconazole, itraconazole, posaconazole or voriconazole
• the HIV protease inhibitors atazanavir,darunavir, nelfinavir, ritonavir, saquinavir or indinavir

The medicines listed below are moderate inhibitors of the enzyme in the liver that breaks down everolimus. These may also increase the blood level of everolimus, which could increase the risk of its side effects. These should be used with caution in people taking everolimus. You should tell your doctor if you get any new or increased side effects if you are prescribed one of these medicines while taking Afinitor:

• amprenavir
• ciclosporin
• diltiazem
• erythromycin
• fluconazole
• fosamprenavir
• verapamil.

The following medicines may increase the breakdown of everolimus by the body and so could decrease the amount of everolimus in the blood, making it less effective. These should be avoided where possible while you are taking Afinitor, but if they can’t be avoided your doctor may need to increase your dose of Afinitor while you are on the combination:

• carbamazepine
• efavirenz
• nevirapine
• phenytoin
• phenobarbital
• rifampicin
• the herbal remedy St John's wort (Hypericum perforatum).

This medicine can decrease the body's immune response. This means that vaccines may be less effective if given during treatment, because the body does not produce sufficient antibodies. Live vaccines may cause serious infections. Live vaccines include: measles, mumps, rubella, MMR, BCG, chickenpox, oral polio, oral typhoid and yellow fever. These should not be given to people whose immune system is underactive due to treatment with this medicine.

Other medicines containing the same active ingredient

There are currently no other medicines available in the UK thatcontain everolimus as the active ingredient.