How does it work?

Yondelis infusion contains the active ingredient trabectedin which is a type of chemotherapy medicine for cancer known as an ‘anti-neoplastic’. Trabectedin is a naturally occurring compound that is derived from a marine organism, Ecteinascidia turbinate.

Cancers form when cells within the body multiply abnormally and uncontrollably. These cells spread, destroying nearby tissues. Trabectedin works by stopping the cancer cells from multiplying. It does this by binding to and damaging the DNA in the cancer cells. This stops the cells from growing and multiplying.

In most chemotherapy regimens, doses are administered in courses at various intervals to allow normal cells to recover from the adverse effects of the anticancer medicines between doses. However, during this period, cancer cells will also recover and start to replicate again. Successful treatment depends on the administration of the next course of therapy before the cancer has regrown to its previous size and the net effect is to decrease the amount of cancer with each successive course.

Trabectedin is used to treat a type of cancer known as soft tissue sarcoma, which affects muscles, fatty tissue and other soft tissue, such as cartilage or blood vessels.

Unfortunately, trabectedin can also affect normal, healthy cells, particularly those that multiply quickly, such as healthy blood cells. Trabectedin is therefore only used to treat soft tissue sarcoma in people who have enough healthy cells in their blood at the start of treatment. Regular blood tests are needed to monitor the levels of blood cells.

Trabectedin is given by slow infusion (drip) into a vein (intravenously) over 24 hours. Dexamethasone is always given before treatment with trabectedin to help reduce sickness and protect the liver. The treatment is repeated every three weeks, for as many courses as your specialist feels is necessary.

What is it used for?

• Soft tissue sarcoma.

This medicine is used when other medicines have not been effective or are unsuitable.

Warning!

• Before each treatment with Yondelis you will need to have blood tests to check your blood cells, liver function, kidney function, bilirubin level and CPK level. These tests should also be carried out weekly during your first two treatments.
• This medicine can cause a decrease in the normal amounts of blood cells in the blood. For this reason you should consult your doctor immediately if you experience any of the following symptoms: unexplained bruising or bleeding, purple spots, sore throat, mouth ulcers, high temperature (fever), feeling tired or general illness. Your doctor may want to take a blood test to check your blood cells.
• This medicine may have side effects on the muscles. For this reason, you should inform your doctor immediately if you experience muscular symptoms such as pain, tenderness, cramps, or weakness while taking this medicine, particularly if they are accompanied by a fever or feeling generally unwell. Your doctor may need to check for side effects on the muscles by taking a blood test to measure the level of a compound called creatinine phosphokinase (CPK) in your blood.
• This medicine may also have side effects on your liver. Symptoms that may suggest a liver problem include persistent nausea and vomiting, abdominal pain, or the development of jaundice (a yellow colouring to the skin and the whites of the eyes). Consult your doctor if you experience any of these symptoms.
• You should not drink alcohol while having treatment with this medicine because this may increase the chance of side effects on the liver.
• This medicine may be harmful to an unborn baby. For this reason, women being treated with this medicine who could get pregnant must use a highly effective method of contraception to prevent pregnancy. You will be given advice on which forms are suitable for you. Contraception should be started before your treatment begins and continued for at least three months after your treatment is finished. You should tell your doctor immediately if you think you could be pregnant at any point during treatment.
• Men being treated with this medicine must use a condom to avoid fathering a child during their treatment and for at least five months after treatment is finished. There is a risk of irreversible infertility associated with Yondelis. For this reason, men should discuss the possibility of sperm conservation with their doctor before starting treatment.

Use with caution in

• Decreased kidney function.
• Decreased liver function or liver disease.

Not to be used in

• Severe or uncontrolled infection.
• Breastfeeding.
• People with high levels of bilirubin (a pigment produced by the liver).
• People with severely decreased kidney function.
• People with low numbers of white blood cells (neutropenia), platelets (thrombocytopenia) or haemoglobin in their blood.
• People with raised liver enzymes or creatinine phosphokinase (CPK) levels.
• This medicine is not recommended for children and adolescents.

This medicine should not be used if you are allergic to one or 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 may cause serious birth defects in a developing baby. It should not be used during pregnancy unless considered essential by your doctor. Effective contraception should be used by women who themselves, or whose male partners, are receiving treatment with this medicine. Women should continue to use this contraception for at least three months after the medicine is stopped. Consult your doctor immediately if you think you could be pregnant.
• Men being treated with this medicine should use condoms to avoid fathering a child, both during treatment and for five months after treatment is finished, if their partner could get pregnant and is not using contraception.
• It is not known if this medicine passes into breast milk. Women should not breastfeed during treatment with this medicine and for three months after stopping the treatment.

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 does not mean that all people using this medicine will experience that or any side effect.

• Disturbances of the gut, such as nausea and vomiting, constipation, diarrhoea, indigestion, abdominal pain.
• Decrease in the numbers of white blood cells (neutropenia), platelets (thrombocytopenia) or red blood cells (anaemia) in the blood.
• Fatigue, weakness or loss of strength (asthenia).
• Loss of appetite and weight loss.
• Headache.
• Elevated levels of liver enzymes.
• Injection site reaction.
• Dizziness.
• Problems with the nerves, for example causing changes in sensation such as pins and needles (paraesthesia) or numbness.
• Shortness of breath (dyspnoea).
• Pain in muscle or joints (myalgia or arthralgia).
• Hair loss (alopecia).
• Fever.
• Low blood pressure (hypotension).
• Swollen ankles (peripheral oedema).
• Difficulty sleeping (insomnia).
• Inflammation of the lining of the mouth (stomatitis).
• Bacterial, viral or fungal infections, sometimes serious.
• Muscle breakdown (rhabdomyolysis).

The side effects listed above may not include all of the side effects reported by the drug'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 having treatment with this one, to ensure that the combination is safe.

There may be an increased risk of side effects on the liver or blood cells if this medicine is used in combination with other medicines that can have these kinds of side effects, or with medicines that can prevent the breakdown of trabectedin in the body (see below for examples).

There may be an increased risk of side effects on the muscles if Yondelis is used in combination with any of the following medicines:

• statins for lowering cholesterol, eg simvastatin, atorvastatin
• fibrates for lowering cholesterol, eg bezafibrate, gemfibrozil
• ezetimibe
• nicotinic acid (niacin)
• medicines that can prevent the breakdown of trabectedin in the body (see below for examples).

The following medicines may prevent the breakdown of trabectedin by the body and so may increase the risk of side effects:

• azole antifungals, eg ketoconazole, fluconazole
• ciclosporin
• macrolide antibiotics, eg clarithromycin.
• protease inhibitors for HIV infection, eg ritonavir
• verapamil.

Trabectedin may decrease the blood level of phenytoin used to treat epilepsy, and this could increase the risk of convulsions. The use of phenytoin in combination with Yondelis is not recommended.

The following medicines may decrease the amount of trabectedin in the blood and could therefore make it less effective:

• phenobarbital
• rifampicin
• the herbal remedy St. John's wort.

Vaccines may be less effective in people receiving chemotherapy. This is because chemotherapy medicines reduce the activity of the immune system and can prevent the body forming adequate antibodies. Live vaccines should be postponed until at least six months after finishing chemotherapy because they may cause serious infections. Live vaccines include: measles, mumps, rubella, MMR, BCG, oral polio, oral typhoid and yellow fever.

Other medicines containing the same active ingredient

There are currently no other medicines available in the UK that contain trabectedin as the active ingredient.