0.25 mg and 1 mg powder to concentrate for infusion solution
trabectedin
What Yondelis is and what it is used for
Yondelis contains the active substance trabectedin. Yondelis is a cancer medicine that works by preventing the tumor cells from multiplying.
Yondelis is used to treat patients with advanced soft tissue sarcoma when previous drug treatment has not been successful or has not been suitable for the patient. Soft tissue sarcoma is a malignant (malignant) disease that begins somewhere in the body’s soft tissues, such as muscles, fat, or other tissues (for example, cartilage or blood vessels ).
Yondelis in combination with pegylated liposomal doxorubicin (PLD: another cancer medicine) is used to treat patients with ovarian cancer, which has come back after at least 1 previous treatment and is not resistant to cancer medicines containing platinum compounds.
What you need to know before you use Yondelis
Do not use Yondelis:
- if you are allergic to trabectedin or any of the other ingredients of this medicine (listed in section 6)
- if you have any serious infection
- if you are breastfeeding
- if you will receive the yellow fever vaccine.
Warnings and precautions
Talk to your doctor before using Yondelis.
Yondelis or its combination with PLD should not be used if you have severe liver, kidney, or heart damage
Tell your doctor if you know or suspect you have any of the following before starting treatment with Yondelis:
- liver or kidney problems
- heart problems or previously had heart problems
- left ventricular ejection fraction (LVEF) below the lower limit of normal
- have previously received treatment with trabectedin in high doses.
Seek immediate medical attention if any of the following occur:
- You get a fever because Yondelis can cause side effects that affect the blood and liver.
- If you feel sick, vomit, or cannot drink anything, and therefore do not urinate as often, despite having been given anti-nausea medication.
- If you get severe muscle pain or weakness, this may be a sign of damage to the muscles ( rhabdomyolysis ); see section 4).
- If you notice that the Yondeli infusion is leaking from the vein while you are receiving it. This can cause the tissue cells around the injection site to be damaged and die (tissue necrosis, see also section 4), which may require surgery.
- If you have an allergic reaction (hypersensitivity). In this case, you may have one or more of the following signs of illness: fever, difficulty breathing, skin redness or rash, feeling sick (nausea), or nausea (vomiting; see section 4).
- If you notice unexplained partial or general swelling (edema), with possible lightheadedness, dizziness, or thirst (low blood pressure ). It may be a sign of a condition (capillary leak syndrome) that can lead to excessive accumulation of fluid in the tissue , and needs prompt medical evaluation.
Children and young people
Yondelis should not be given to children under 18 years of age with pediatric sarcomas.
Other medicines and Yondelis
Tell your doctor or pharmacist if you are using, have recently used, or might be using other medicines.
You must not use Yondelis if you are to receive the yellow fever vaccine and it is not appropriate to take Yondelis if you are receiving a vaccine that contains live virus particles. The effect of medicines containing phenytoin (for epilepsy ) can be reduced if it is given together with Yondelis and therefore simultaneous treatment is not suitable.
If you are taking any of the following medicines during your treatment with Yondelis, you need to be closely monitored as it may lead to the effects of Yondelis:
- decreases (for example, if you take medicines containing rifampicin (for bacterial infections), phenobarbital (for epilepsy ), or St. John’s wort ( Hypericum perforatum, herbal medicine for depression)), or
- increases (for example if you take medicines containing ketoconazole or fluconazole (for fungal infections), ritonavir (for infection with the human immunodeficiency virus ( HIV )), clarithromycin (for bacterial infections), aprepitant (to prevent nausea and vomiting), ciclosporin (suppresses the body’s immune system ) or verapamil (for high blood pressure and heart problems)).
Use of these medicines together with Yondelis should therefore be avoided if possible.
If you receive Yondelis or the Yondelis+PLD combination together with a medicine that can cause liver or muscle damage ( rhabdomyolysis ), you may need to be closely monitored, as there may be an increased risk of liver or muscle damage. Drugs containing statins (to lower cholesterol levels and prevent cardiovascular disease) are examples of drugs that can cause muscle damage.
Yondelis with alcohol
Alcohol consumption should be avoided during treatment with Yondelis as this may damage the liver.
Pregnancy, breastfeeding, and fertility
Pregnancy
Yondelis should not be used during pregnancy. If you are pregnant, think you may be pregnant, or are planning to have a baby, consult your doctor before using this medicine.
Women of childbearing potential must use effective contraception during treatment and for 3 months afterward.
In the event of pregnancy, you must tell your doctor immediately and genetic counseling is recommended as Yondelis can cause genetic damage.
Breast-feeding
Yondelis must not be given to patientsbreastfeeding. Therefore, you must stop breastfeeding before starting treatment and you must not start breastfeeding again until your doctor has confirmed that it is safe for you to do so.
Fertility
Effective contraception must be used by fertile men for 5 months after the end of treatment.
Patients should be advised about the preservation of eggs or sperm before treatment as there is a risk of permanent infertility due to treatment with Yondelis.
Genetic counseling is also recommended for patients who wish to have children after completing treatment.
Driving ability and use of machinery
During treatment with Yondelis, you may feel tired and experience weakness. You should not drive or use machines if you suffer from any of these side effects.
Yondelis contains potassium
This medicine contains less than 1 mmol (39 mg) of potassium per vial, i.e. it is almost “potassium-free”.
How to use Yondelis
Yondelis is given under the supervision of a doctor experienced in chemotherapy. Administration may only be performed by trained oncologists or other healthcare personnel, who are specially trained in the administration of chemotherapy.
For the treatment of soft tissue sarcoma, the dose is usually 1.5 mg/m² body surface. Throughout the treatment period, your doctor will closely follow you with checks and determine the dosage of Yondelis that is most suitable for you. The recommended dose for Japanese patients is lower than the usual dose for all other ethnicities and is 1.2 mg/m 2 body surface.
For the treatment of ovarian cancer, the usual dose is 1.1 mg/m 2 body surface after administration of 30 mg/m 2 body surface of PLD.
Before you receive Yondelis, the medicine is prepared and diluted for intravenous use. Each time you receive Yondelis for soft tissue sarcoma, it takes about 24 hours for all of the solutions to enter your bloodstream. The treatment of ovarian cancer takes three hours.
To avoid irritation at the injection site, it is recommended that Yondelis is given to you via a central venous line.
You will be given another medicine before treatment and, if necessary, during treatment with Yondelis to protect the liver and reduce the risk of nausea and vomiting.
You will receive an infusion every three weeks, although the doctor sometimes recommends a dose delay to ensure that you receive the dose of Yondelis that is best for you.
The total length of the treatment period depends on how your condition develops and how you feel. Your doctor will tell you how long the treatment will last. If you have any further questions about this medicine, contact your doctor.
Possible side effects
Like all medicines, this medicine or its combination with PLD can cause side effects, although not everybody gets them.
If you are not sure what the side effects below mean, you should ask your doctor to explain them to you in more detail.
Serious side effects caused by treatment with Yondelis:
Very common (may affect more than 1 in 10 users)
- You may have increased levels of the yellow pigment bilirubin in the blood, which can cause jaundice (yellowing of the skin, mucous membranes, and eyes).
- Your doctor will prescribe regular blood tests to detect any abnormal blood values.
Common (may affect up to 1 in 10 users)
- You can also get blood infections ( sepsis ) if you have a severely compromised immune system. If you develop a fever, you must seek medical attention immediately.
- You may also experience pain in the muscles ( myalgia ). You can also have nerve damage that can result in muscle pain, weakness and numbness. You may become swollen in the body or get swollen legs and a crawling sensation in the skin.
- You may react to the injection site. Yondeli’s infusion may leak out of the vein when you receive it, causing the tissue cells around the injection site to be damaged and die (tissue necrosis, see also section 2 “Warnings and precautions”), which may require surgery.
- You may have an allergic reaction. You may have a fever, difficulty breathing, skin redness or rash, feeling sick (nausea), or sick (vomiting).
- When Yondelis is used in combination with PLD, you may suffer from syncope, also known as a fainting fit. You may also experience the heart beating too hard or too fast (palpitations), the heart chambers may become weaker (left ventricular dysfunction), or a pulmonary artery may become blocked ( pulmonary embolism ).
Uncommon (may affect up to 1 in 100 users)
- You may experience severe muscle aches and pains, stiffness, and muscle weakness. Your urine may also become darker in color. Everything described above could be a sign of damage to your muscles ( rhabdomyolysis ).
- The doctor may want to take a blood test in certain situations to avoid you developing muscle damage ( rhabdomyolysis ). In very severe cases, this can lead to kidney failure. If you develop severe muscle pain or weakness, you must seek medical attention immediately.
- You may experience difficulty breathing, irregular heartbeat, decreased urine output, sudden changes in your mental state, areas of mottled skin, and extremely low blood pressure associated with abnormal laboratory values (decreased platelet counts ). If you experience any of the above-mentioned symptoms or signs of illness, seek medical attention immediately.
- You may suffer from an abnormal fluid build-up in the lungs that leads to swelling ( pulmonary edema).
- If you notice unexplained partial or general swelling (edema), with possible lightheadedness, dizziness, or thirst (low blood pressure ). It may be a sign of a condition (capillary leak syndrome) that can lead to excessive fluid accumulation in tissue. If you experience any of the above-mentioned symptoms or signs, seek medical attention immediately.
- You may notice that the Yondeli infusion solution leaks out of the vein (extravasation) when it is given to you. You will then notice some redness, swelling, itching, and discomfort at the injection site. If you get any of these symptoms or signs, talk to a nurse or doctor immediately.
This can cause the cells in the tissue around the injection site to be damaged or die (tissue necrosis), which may require surgery.
Some of the symptoms or signs of extravasation may not appear until several hours after the extravasation has occurred. There may be blistering, peeling, and darkening of the skin over the site. It may take a few days before the full extent of the tissue damage is visible. If you experience any of the symptoms or signs described above, seek medical attention immediately.
Rare (may affect up to 1 in 1,000 users)
- The skin and whites of the eyes may turn yellow (jaundice), and you may have pain in the upper right part of the abdomen, nausea, vomiting, general malaise, difficulty concentrating, feeling disoriented or confused, and sleepiness. These signs of disease may be an indication of the liver’s inability to function normally. If you experience any of the symptoms or signs of illness described above, seek medical attention immediately.
Other less serious side effects are
Very common (may affect more than 1 in 10 users)
- You can:
- feel tired
- have difficulty breathing and cough
- get back pain
- get fluid accumulation in the body ( edema )
- get more bruises than normal
- nosebleeds
- get infection more easily. An infection can also give you an elevated body temperature (fever). If you experience any of these symptoms, you must seek medical attention immediately.
- You may have digestive symptoms such as loss of appetite, nausea or vomiting, abdominal pain, diarrhea, or constipation. If you become nauseous, vomit, or cannot drink anything and therefore do not urinate very often, despite taking anti-nausea medication, you must seek medical attention immediately.
- You may get a headache.
- You may get inflammation of the mucosa such as red swellings inside the mouth leading to painful sores and mouth ulcers, inflammation of the mouth ( stomatitis ), or inflammation of the gastrointestinal tract when Yondelis is used at the same time as PLD.
- Patients receiving Yondelis plus PLD for ovarian cancer may experience hand or foot problems. It can appear as red skin on the palms of the hands, fingers, and soles of the feet which later swells and turns blue-purple. The changes can either dry out and scale or form blisters with sores.
Common (may affect up to 1 in 10 users)
- You may experience loss of fluid from the body, weight loss, indigestion, and an altered sense of taste.
- You may lose hair.
- You may also experience dizziness, low blood pressure, and flushing, or skin rash.
- More severe skin pigmentation may occur in patients receiving Yondelis at the same time as PLD for ovarian cancer.
- You may experience joint pain.
- You may have trouble sleeping.
How to store Yondelis
Keep this medicine out of the sight and reach of children.
Use before the expiry date which is stated on the carton and vial label after EXP. The expiration date is the last day of the specified month.
Store in a refrigerator (2 ºC–8 ºC).
Information on stability when using reconstituted and diluted solutions are provided in the section for healthcare professionals.
Do not use this medicine if you observe visible particles after reconstitution or dilution of the medicine.
Unused medicine and waste must be disposed of according to current instructions for cytotoxic medication.
Contents of the packaging and other information
Contents declaration
- The active substance is trabectedin.
Yondelis 0.25 mg: Each vial of powder contains 0.25 mg of trabectedin.Yondelis 1 mg: Each vial of powder contains 1 mg of trabectedin - Other ingredients are sucrose, potassium dihydrogen phosphate, phosphoric acid (for pH adjustment), and potassium hydroxide (for pH adjustment).
Appearance and package sizes of the medicine
Yondelis is a powder to concentrate to infusion liquid, solution. The powder is white to off-white and is supplied in a glass vial.
Each outer carton contains 1 vial of either 1 mg or 0.25 mg trabectedin.
Pharma Mar, SA
Abda. de Los Reyes 1
Polígono Industrial La Mina
28770 Colmenar Viejo (Madrid)
SPAIN
Phone: +34 91 846 60 00
Fax: +34 91 846 60 01
Contact the marketing authorization holder if you want to know more about this medicine.