How does it work?

Torisel infusion contains the active ingredient temsirolimus, 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.

Temsirolimus 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.

Temsirolimus is licensed to treat advanced kidney cancer and mantle cell lymphoma. The medicine is given by a drip into a vein (intravenous infusion) over 30 to 60 minutes. It is given once a week. You will be given an injection of an antihistamine before each infusion to minimise any reactions to it.

What is it used for?

• Advanced kidney cancer (renal cell carcinoma).
• Mantle cell lymphoma that has come back (relapsed) after previous treatment or has not responded to other treatments.

Warning!

• You should avoid drinking grapefruit juice while being treated with 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 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, your doctor may want you to stop taking this medicine before going to have any major surgical procedures or operations. Follow the instructions given by your doctor.
• If you get a sudden new or worsening cough, high temperature (fever), wheezing or shortness of breath while taking this medicine, you should let your doctor know, as these could be symptoms of a rare form of lung irritation called interstitial lung disease, which can be a side effect of this medicine.
• 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 being treated with this medicine. Men receiving this medicine should use effective contraception to prevent fathering a child. Seek further medical advice from your doctor. Tell your doctor immediately if you get pregnant during treatment.
• This medicine contains alcohol and should be used with caution in people suffering from alcoholism, liver disease or epilepsy. If you are receiving the higher dose of this medicine to treat mantle cell lymphoma, the amount of alcohol in each dose may impair your ability to drive or operate machinery.

Use with caution in

• People who are allergic to antihistamines or who can’t take antihistamines for other medical reasons.
• Severely decreased kidney function.
• Decreased liver function.
• People with diabetes.
• People with high cholesterol levels.
• People with a tumour in the brain or spinal cord.
• People taking anticoagulant medicines such as warfarin.
• People who have recently had surgery.

Not to be used in

• People with moderate to severely decreased liver function being treated for mantle cell lymphoma.
• Breastfeeding.
• This medicine is not recommended for children and adolescents, 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 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 being treated with this medicine. Men receiving treatment should also use contraception to avoid fathering a child. 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 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.

• Increased susceptibility to infection due to decrease in number of white blood cells.
• High blood glucose level (hyperglycaemia).
• Elevated levels of cholesterol or triglycerides in the blood.
• Increased clotting time of blood.
• Weakness or loss of strength (asthenia).
• Swelling due to fluid retention (oedema).
• Pain in the muscles and joints.
• Disturbance of the gut such as nausea, diarrhoea, abdominal pain, indigestion.
• Sore throat and/or mouth.
• Runny nose or nose bleeds.
• Skin reactions such as rash, itching, acne.
• Loss of appetite.
• Decreased level of potassium in the blood (hypokalaemia).
• Anaemia.
• Anxiety.
• Changes in taste.
• Difficulty falling asleep (insomnia).
• Fever.
• Interstitial lung disease.
• Slow wound healing.
• Chest pain.
• Swelling and redness of gums.
• Inflammation of hair follicles (folliculitis).
• Bloating of stomach.
• High blood pressure.
• Dizziness.
• Depression.
• Eye disorders.
• Drowsiness.
• Low blood phosphate levels (hypophosphataemia).
• Kidney failure.
• Perforation (hole) in the bowel.
• Bleeding in the gut.
• Hypersensitivity reactions which may include symptoms such as chest pain, difficulty in breathing, low blood pressure, flushing.

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 medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines while being treated with this one, to make sure that the combination is safe.

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

• amiodarone
• aprepitant
• the antibiotic medicines clarithromycin, erythromycin and telithromycin
• the antifungal medicines ketoconazole, itraconazole and voriconazole
• diltiazem
• HIV protease inhibitors such as atazanavir, nelfinavir, ritonavir, saquinavir and indinavir
• verapamil.

The medicines listed below may decrease the blood level of temsirolimus, which could make it less effective. These medicines should also be avoided where possible while you are having treatment with temsirolimus. The manufacturer recommends people being treated for kidney cancer should not take any of these continuously for longer than 5 to 7 days, while people being treated for mantle cell lymphoma should not take them at all as they need a higher dose of the medicine.

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

Temsirolimus may reduce the removal of the following medicines from the body and so may increase the blood levels and risk of side effects of these medicines:

• colchicine
• digoxin
• paclitaxel
• vincristine.

Using ACE inhibitors, such as lisinopril and ramipril with temsirolimus can increase the risk of an allergic reaction called angioedema. Therefore, ACE inhibitors must be used with caution for people having treatment with Torisel.

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 temsirolimus as the active ingredient.