Yondelis 0.25 mg powder for concentrate for solution forinfu - United Kingdom[英国药品]

TOP

Yondelis 0.25 mg powder for concentrate for solution forinfu

2014-07-12 18:59:16 来源: 作者: 【大中小】浏览:324次评论:0条

For doctors

What is it and how is it used?

Yondelis is an anti-cancer medicine that works by preventing the tumour cells from multiplying.

Yondelis is used for the treatment of patients with advanced soft tissue sarcoma, when previous medicines have been unsuccessful or the patients are unsuited to receive them. Soft tissue sarcoma is a malignant disease that starts somewhere in the soft tissues, such as the muscles, fat or other tissues (for example cartilages or vessels).

Yondelis in combination with pegylated liposomal doxorubicin (PLD: another anti-cancer medicine) is used for the treatment of patients with ovarian cancer that has come back after at least 1 previous therapy and are not resistant to platinum based anti-cancer medicines.

What do you have to consider before using it?

Do not use Yondelis:

Take special care with Yondelis:

Yondelis or its combination with PLD must not be used if you have severe liver or kidney damage. Tell your doctor if you know or suspect that you have any liver or kidney problems before starting the treatment with Yondelis.

You should seek medical attention immediately if any of the following conditions appear:

If you develop a fever as Yondelis may cause side-effects affecting your blood and liver.

If you still feel sick, vomit or are unable to drink fluids and therefore pass less urine despite being given anti-sickness medicines.

If you experience severe muscle pain or weakness as it could be a sign of damage to your muscles rhabdomyolysis see section 4.

If you notice that Yondelis infusion leaks out of your vein while you are being given it. It could lead to damage and death of your tissue cells around the injection site tissue necrosis, see also section 4 which may require surgery.

Yondelis must not be used in children and adolescents since safety and efficacy have not yet been studied in this age group.

Using other medicines

Please tell your doctor if you plan to take, are taking or have recently taken any other medicines, including medicines obtained without a prescription, vaccines and herbal medicines.

You must not use Yondelis if you will receive yellow fever vaccine and it is not recommended that you use Yondelis if you will receive a vaccine containing live virus particles. The effect of medicines containing phenytoin (for epilepsy) may be decreased if given together with Yondelis and this is therefore not recommended.

If you use other medicines, you may need to be closely monitored as the effects of Yondelis might be decreased (examples are medicines containing rifampicin (for bacterial infections), phenobarbital (for epilepsy) or St. John´s Wort ( Hypericum perforatum, an herbal medicine for depression)) or increased (examples are medicines containing ketoconazole or fluconazole (for fungal infections), ritonavir (for HIV infection), clarithromycin (for bacterial infections), aprepitant (to prevent nausea and vomiting), ciclosporin (inhibit the defensive system of the body) or verapamil (for high blood pressure and heart conditions)) as a result.

If you are given Yondelis or the combination Yondelis+PLD together with a medicine that might cause damage to the liver or to the muscles (rhabdomyolysis), you may need to be closely monitored, when using Yondelis together with this medicine, as there could be an increased risk of damage. Medicines containing statins (for lowering cholesterol levels and preventing cardiovascular disease) is an example of medicines that may cause muscle damage.

Using Yondelis with food and drink

Alcohol consumption must be avoided during treatment with Yondelis as this may harm the liver.

Pregnancy and breast-feeding

Pregnancy

You should not use Yondelis if you are pregnant or if you are trying to become pregnant as Yondelis may harm the unborn baby. If you are pregnant or you think you may be pregnant, you must tell your doctor immediately. The doctor may prescribe Yondelis during pregnancy in certain circumstances.

Adequate contraceptive precautions must be used by men in fertile age and women of childbearing potential when receiving Yondelis and for 3 months following the end of treatment for women and 5 months following the end of treatment for men. If a pregnancy should occur you must tell your doctor immediately and genetic counselling is recommended since Yondelis can cause genetic damage.

Genetic counselling is also recommended for patients wishing to have children after therapy. Male patients should seek advice on sperm conservation prior to treatment because of the risk of irreversible infertility due to therapy with Yondelis.

Breast-feeding

Yondelis must not be given to patients who are breast-feeding. Therefore you must stop breast-feeding before you start your treatment and you must not begin breast-feeding again until your doctor has confirmed that it is safe to do so.

Driving and using machines

During your treatment with Yondelis you may feel tired and experience a loss of strength. Do not drive or use any tools or machines if you are experiencing any of these side effects.

Important information about some of the ingredients of Yondelis

This medicine contains potassium, less than 1 mmol (39 mg) per vial, and can therefore be considered as essentially “potassium-free”.

How is it used?

Yondelis is given to you under the supervision of a physician experienced in the use of chemotherapy. Its use should be confined to qualified oncologists or other health professionals specialised in the administration of cytotoxic medicines.

For the treatment of soft tissue sarcoma, the usual dose is 1.5 mg/m of body surface area. During the treatment period, your doctor will carefully monitor you and decide the most appropriate dosage of Yondelis to give to you.

For the treatment of ovarian cancer, the usual dose is 1.1 mg/m body surface area after the administration of 30 mg/m body surface area of PLD.

Before Yondelis is given to you, it is reconstituted and diluted for intravenous use. Every time you are given Yondelis for the treatment of soft tissue sarcoma, it will take about 24 hours for all of the solution to enter your blood. It will take 3 hours for the treatment of ovarian cancer.

In order to avoid irritation at the site of injection it is recommended that Yondelis is given to you through a central venous line.

You will be given medicine before and as needed during the treatment with Yondelis in order to protect your liver and to reduce the risk of side effects such as feeling sick (nausea) and vomiting.

The infusion is given to you every 3 weeks, although occasionally your doctor may recommend dose delays to ensure that you receive the most appropriate dosage of Yondelis.

The length of your whole treatment period will depend on your progress and how well you feel. Your doctor will tell you how long your treatment lasts. If you have any further questions on the use of this medicine, ask your doctor.

What are possible side effects?

Like all medicines, Yondelis or its combination with PLD can cause side effects, although not everybody gets them.

If you are not sure what the side effects below are, you should ask your doctor to explain them to you in more detail.

Side effects caused by the single treatment with Yondelis:

Very common (occurring in at least 1 in 10 patients):

You could have coughing.

You may lose hair alopecia.

You could also experience dizziness, sleeping problems, low blood pressure and flushing.

You may have a reaction at the site of injection. Yondelis infusion may leak out of your vein while you are being given it, leading to damage and death of your tissue cells around the injection site tissue necrosis, see also section 2 Take special care with Yondelis which may require surgery.

Other side effects that may occur with the combination of Yondelis and PLD:

When Yondelis is used in combination with PLD some of these side effects are more likely to occur and some may occcur in a more severe way.

Very common (occurring in at least 1 in 10 patients):

You may have the hand and foot syndrome. It may present as red skin of the palms, fingers, and soles of the feet that later may become swelling and violaceous. The lesions may either dry out and desquamate, or blister with ulceration.

Common (occurring in at least 1 in 100 patients):

You may have a higher skin pigmentation and rash. You could have mucosal inflammation as a swelling redness of the inside of the mouth leading to painful ulcers and mouth sores or as an inflammation of the gastrointestinal tract.

You may also have blood infections neutropenic infection and neutropenic sepsis. Your doctor will order regular blood tests to detect any abnormalities in the blood.

You may have syncope also called fainting.

You could have a weakness in the ventricles, the hearts major pumping chambers left ventricular dysfunction, sudden blockage in a lung artery pulmonary embolism and an abnormal build up of fluid in the lungs, which leads to swelling pulmonary oedema.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

How should it be stored?

Keep out of the reach and sight of children.

Do not use Yondelis after the expiry date which is stated on the carton and the vial label after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2ºC - 8ºC).

Information on in-use stability of the reconstituted and diluted solutions is included in the section for medical and healthcare professionals.

↑ back to table of contents ↑

For doctors

What is it?

Yondelis is a powder that is made up into a solution for infusion (drip into a vein). It contains the active substance trabectedin.

What is it used for?

Yondelis is used to treat adults with two types of cancer:
- advanced soft-tissue sarcoma, a type of cancer that develops from the soft, supporting tissues of the body. ‘Advanced’ means that the cancer has started to spread. Yondelis is used when treatment with anthracyclines and ifosfamide (other anticancer medicines) have stopped working, or in patients who cannot be given these medicines;
- ovarian cancer (cancer of the ovaries) that has relapsed (come back after previous treatment) and is sensitive to medicines containing platinum. Yondelis is used in combination with pegylated liposomal doxorubicin (PLD, another anticancer medicine).
Because the numbers of patients with soft-tissue sarcoma and ovarian cancer are low, the diseases are considered ‘rare’, and Yondelis was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 30 May 2001 (for soft-tissue sarcoma) and on 17 October 2003 (for ovarian cancer). The medicine can only be obtained with a prescription.

How is it used?

Yondelis must be given under the supervision of a doctor who is experienced in the use of chemotherapy (medicines to treat cancer). It should only be used by qualified oncologists (cancer specialists) or other health professionals who are specialised in giving cytotoxic (cell-killing) medicines.
For soft-tissue sarcoma, the recommended dose of Yondelis is 1.5 mg per square metre of body surface area (calculated using the patient’s height and weight), given as a single infusion lasting 24 hours every three weeks. For ovarian cancer, it is given at a dose of 1.1 mg/m every three weeks as an infusion lasting three hours, immediately after the PLD infusion.
Treatment carries on for as long as the patient shows a benefit. It is recommended that Yondelis be given through a central venous line (a thin tube leading from the skin into the large veins just above the heart). To prevent vomiting and to protect the liver, patients must receive an infusion of corticosteroids such as dexamethasone before treatment. If the patient’s blood counts are abnormal, infusion with Yondelis should be delayed, the dose of Yondelis should be reduced or other medicines can be used to treat the blood problems. For more information, see the Summary of Product Characteristics (also part of the EPAR).

How does it work?

The active substance in Yondelis, trabectedin, is an anticancer medicine. It is a synthetic version of a substance that was originally extracted from a species of tunicate or ‘sea squirt’ (a marine animal). Cancer is a disease where cells divide too quickly, usually because the way their genes work is faulty. Trabectedin works by attaching to the DNA, the chemical molecule that makes up genes, and preventing some genes in human cells from increasing their activity. This can prevent the cells from dividing too quickly, slowing down the growth of various types of cancer.

How has it been studied?

For soft-tissue sarcoma, Yondelis has been studied in one main study involving 266 patients with liposarcoma (a sarcoma originating in fat cells) or leiomyosarcoma (a sarcoma originating in ‘smooth’ or involuntary muscle cells) that was advanced or metastatic (had spread to other parts of the body). All of the patients had been treated previously with an anthracycline and ifosfamide but this treatment had stopped working. The study compared two different dosing schedules of Yondelis: three times per month, or once every three weeks.
For ovarian cancer, Yondelis in combination with PLD was compared with PLD alone in one main study involving 672 women whose disease had come back or got worse after previous treatment. Around two-thirds of the patients had cancer that was sensitive to platinum-containing medicines. In both studies, the main measure of effectiveness was how long the patients lived without their disease getting worse.

What benefits has it shown during the studies?

For soft-tissue sarcoma, Yondelis was more effective when it was given once every three weeks than when it was given with the alternative dosing schedule. Patients receiving it once every three weeks lived for an average of 3.8 months without their disease getting worse, compared with 2.1 months in those receiving Yondelis three times per month.
For ovarian cancer, the combination of Yondelis and PLD was more effective than PLD alone: the patients receiving the combination treatment lived for an average of 7.3 months without their disease getting worse, compared with 5.8 months in those receiving PLD alone. The effect of Yondelis was more pronounced in the women whose cancer was sensitive to platinum-containing medicines.

What is the risk associated?

The most common side effects with Yondelis when used on its own for soft-tissue sarcoma (seen in more than 1 patient in 10) are increased blood levels of creatine phosphokinase (a marker of muscle breakdown) and of creatinine (a marker of kidney problems), decreased blood levels of albumin (a marker of liver problems), neutropenia (low levels of neutrophils, a type of white blood cell), thrombocytopenia (low blood platelet counts), anaemia (low red blood cell counts), leucopenia (low white blood cell counts), headache, vomiting, nausea (feeling sick), constipation, loss of appetite, fatigue (tiredness), asthenia (weakness), hyperbilirubinaemia (high levels of bilirubin in the blood) and increased levels of liver enzymes in the blood. Side effects were similar when Yondelis was used together with PLD for ovarian cancer, although palmar-plantar erythrodysaesthesia syndrome (rash and numbness on the palms and soles) and mucosal inflammation (inflammation of the moist body surfaces) seemed to be more common. For the full list of all side effects reported with Yondelis, see the Package Leaflet.
Yondelis should not be used in people who may be hypersensitive (allergic) to trabectedin or any of the other ingredients. It must not be used in patients who have any serious or uncontrolled infection, in combination with the vaccine for yellow fever, or in breast-feeding women.

Why has it been approved?

The Committee for Medicinal Products for Human Use (CHMP) concluded that Yondelis’s benefits are greater than its risks and recommended that it be given marketing authorisation. Yondelis has been authorised under ‘Exceptional Circumstances’. This means that because soft tissue sarcoma is rare, it has not been possible to obtain complete information about Yondelis. Every year, the European Medicines Agency will review any new information that may become available and this summary will be updated as necessary.

How has it been studied?

The company that makes Yondelis will continue to assess which patients with soft tissue sarcoma are more likely to respond to the medicine.

Further information

The European Commission granted a marketing authorisation valid throughout the European Union for Yondelis to Pharma Mar, S.A. on 17 September 2007. The marketing authorisation is valid for five years, after which it can be renewed.

The summaries of opinion of the Committee for Orphan Medicinal Products are available here (soft-tissue sarcoma) and here (ovarian cancer).

↑ back to table of contents ↑