YONDELIS 025 mg Proszek I Rozpuszczalnik Do Roztworu Do Infuzji Dożylnej

Treść ulotki

1. Yondelis 0.25 mg powder for concentrate for solution for infusion, 1 mg powder for concentrate for solution for infusion.
   1. What is Yondelis and what is it used for
   2. What you need to know before you use Yondelis
   3. How to use Yondelis
   4. Possible side effects
   5. How to store Yondelis
   6. Package contents and other information

Yondelis 0.25 mg powder for concentrate for solution for infusion, 1 mg powder for concentrate for solution for infusion.

trabectedina

Read this leaflet carefully before you start to use this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• If you get any side effects, even those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

• 1. What Yondelis is and what it is used for
• 2. What you need to know before you use Yondelis
• 3. How to use Yondelis
• 4. Possible side effects
• 5. How to store Yondelis
• 6. Contents of the pack and other information

1. What is Yondelis and what is it used for

Yondelis contains the active substance trabectedine. Yondelis is an antitumoral medicine that
prevents the multiplication of tumor cells.
Yondelis is used for the treatment of patients who present with an advanced soft tissue sarcoma who
have not benefited from the use of other medicines or who cannot receive them. Soft tissue sarcoma is a malignant disease that originates in any point of the soft tissues,
such as in muscles, fat or other tissues (for example cartilages or vessels).
Yondelis associated with liposomal doxorubicin pegylated (PLD: another antitumoral medicine)
is used for the treatment of patients who present with a recurrence (reappearance) of ovarian
cancer after administration of at least one previous therapy and who are not resistant to
antitumoral medicines containing platinum compounds.

2. 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 a severe infection.
• if you are breastfeeding.
• if you are planning to get vaccinated against yellow fever.

Warnings and precautions
Talk to your doctor before using Yondelis.
Yondelis, alone or in combination with PLD, should not be used in cases of severe liver, kidney or heart damage.
Contact your doctor if you have or suspect any of the following conditions before starting treatment with Yondelis:

• Liver or kidney problems.
• Heart problems or a history of heart problems.
• Left ventricular ejection fraction (LVEF) below the lower limit of normal.
• If you have previously received high-dose anthracycline treatment.

Contact your doctor immediately if you experience any of the following conditions:

• If you have a fever, as Yondelis can cause side effects that also affect the blood and liver.
• If you feel unwell, have vomiting or are unable to drink fluids with decreased urine production despite the administration of anti-nausea medications.
• If you have severe muscle pain or weakness, which could be a sign of muscle damage (rhabdomyolysis: see section 4).
• If you notice leakage of the Yondelis solution from the vein during the infusion of the medicine. This can cause damage and destruction of cells in the tissues around the injection site (tissue necrosis, see also section 4) which may require surgery to remove the damaged tissue.
• In case of an allergic reaction (hypersensitivity). In such a situation, you may experience one or more of the following signs: fever, difficulty breathing, skin redness, flushing or rash, feeling unwell (nausea) or feeling sick (vomiting; see section 4).
• If you notice swelling, partial or generalized (edema) with possible dizziness, lightheadedness or thirst (low blood pressure). This may be a sign of a condition (capillary leak syndrome) that can cause excessive fluid accumulation in the tissues and requires urgent evaluation by your doctor.

Children and adolescents
Yondelis should not be used in children under 18 years of age with pediatric sarcomas.

Other medicines and Yondelis
Tell your doctor if you are taking, have recently taken or might take any other medicines.
You should not use Yondelis if you are going to receive the yellow fever vaccine, and Yondelis is not recommended if you are going to receive a vaccine containing live viral particles. The effect of medicines containing phenytoin (for epilepsy) may be reduced if administered together with Yondelis, and therefore the combination is not recommended.
If you are using any of the following medicines during treatment with Yondelis, close monitoring is necessary as the effects of Yondelis may be:

• decreased (some examples are medicines containing rifampicin (for bacterial infections), phenobarbital (for epilepsy) or St. John's Wort (Hypericum perforatum, a herbal medicine for depression)) or
• increased (some examples are medicines containing ketoconazole or fluconazole (for fungal infections), ritonavir (for human immunodeficiency virus, humanimmunodeficiency virus,HIV infections), clarithromycin (for bacterial infections), aprepitant (to prevent nausea and vomiting), cyclosporine (suppresses the body's defense system) or verapamil (for high blood pressure and heart conditions)).

Therefore, the use of any of these medicines with Yondelis should be avoided if possible.
If you have been prescribed Yondelis or Yondelis+PLD together with a medicine that can cause liver or muscle damage (rhabdomyolysis), close monitoring may be necessary, as there may be an increased risk of liver or muscle damage. Medicines containing statins (to lower cholesterol levels and prevent cardiovascular diseases) are an example of a medicine that can cause muscle damage.

Yondelis with alcohol
Avoid consuming alcohol during treatment with Yondelis as this could damage the liver.

Pregnancy, breastfeeding and fertility
Pregnancy
Yondelis should not be used during pregnancy. If you are pregnant, suspect you may be pregnant or are planning to become pregnant, ask your doctor for advice before taking this medicine.
Women of childbearing potential must use effective contraceptive methods during the administration of Yondelis and for 3 months after treatment.
In case of pregnancy, inform your doctor immediately and genetic counseling is recommended because Yondelis can cause genetic damage.
Breastfeeding
Yondelis should not be administered to patients who are breastfeeding. Therefore, you should stop breastfeeding before starting treatment and do not resume it until your doctor has confirmed the complete absence of risk.
Fertility
Men of childbearing potential must use effective contraceptive methods during treatment with Yondelis and for 5 months after treatment.
Patients are advised to consider the possibility of preserving eggs and sperm before treatment due to the risk of irreversible infertility due to Yondelis therapy.
Genetic counseling is also recommended for all patients who wish to have a child after therapy.

Driving and operating machinery
During treatment with Yondelis, you may experience fatigue and loss of strength. Do not drive or use any tools or machinery if you experience these side effects.

Yondelis contains potassium
This medicine contains potassium, less than 1 mmol (39 mg) per vial, i.e. essentially ‘potassium-free’.

3. How to use Yondelis

Yondelis is administered under the supervision of a doctor experienced in the use of chemotherapy.
Its use should be limited to qualified oncologists or other healthcare professionals
specialized in the administration of cytotoxic drugs.
For the treatment of soft tissue sarcoma, the usual dose is 1.5 mg/m of body surface area.
During the treatment period, the doctor will monitor you closely and decide the dose of
Yondelis most appropriate to administer. The recommended dose for Japanese patients is lower
than the usual dose used in all other ethnicities and corresponds to 1.2 mg/m of body surface
area.
For the treatment of ovarian cancer, the usual dose is 1.1 mg/m of body surface area after
administration of PLD at a dose of 30 mg/m of body surface area.
Before the administration of Yondelis, it is reconstituted and diluted for infusion for intravenous
use. Each time you are administered Yondelis for the treatment of soft tissue sarcoma, it will take approximately 24 hours to complete the passage of the solution into the bloodstream. It will take 3 hours for the treatment of ovarian cancer.
To avoid any possible irritation at the injection site, it is recommended to administer Yondelis
through a central venous line.
You will be given some medications, before treatment with Yondelis and as needed, to
protect the liver and reduce the risk of side effects such as nausea and vomiting.
The infusion is repeated every 3 weeks, although occasionally the doctor may recommend delaying
administration to ensure that you receive the appropriate dose of Yondelis.
The length of the entire treatment period will depend on the progression of the disease and your
state of health. The doctor will decide the duration of treatment. If you have any doubts about the use of
this medicine, please consult your doctor.

4. Possible side effects

Like all medicines, this medicine, or its association with PLD, can cause side effects, although not everybody gets them.
If you have any doubts about the side effects listed below, ask your doctor for a more detailed explanation.
Serious side effects caused by treatment with Yondelis:

Very common: may affect more than 1 in 10 people

• You may experience increased levels of the yellow pigment bilirubin in the blood, with related jaundice (yellowing of skin, mucous membranes and eyes).
• Your doctor will prescribe blood tests on a regular basis to detect any abnormalities in the blood.

Common: may affect up to 1 in 10 people

• You may also develop blood infections (sepsis) if your immune system is severely compromised. If you experience a temperature increase, inform your doctor immediately.
• You may have muscle pain (myalgia). Nerve damage with related muscle pain, weakness and soreness may also occur. General swelling, swelling of the limbs and a sensation of chills on the skin may occur.
• A reaction may occur at the injection site. The Yondelis infusion solution may leak from the vein during administration of the medicine, causing damage and destruction of the cells of the tissues around the injection site (tissue necrosis, see also section 2 “Warnings and precautions”) which may require surgery to remove the damaged tissue.
• You may have an allergic reaction. In this case, you may experience fever, difficulty breathing, skin redness, flushing or rash, feeling unwell (nausea) or vomiting.
• When Yondelis is used in combination with PLD, syncope, also defined as fainting, may occur. In addition, you may feel that your heart is beating too hard or too fast (palpitations), weakness in the ventricles, the main heart cavities for pumping (left ventricular dysfunction) or a sudden blockage in a pulmonary artery (pulmonary embolism).

Uncommon: may affect up to 1 in 100 people

• Severe muscle pain, stiffness and muscle weakness may occur. You may also notice a dark coloration of the urine. All of the effects described above may be a sign of muscle damage (rhabdomyolysis).
• Your doctor may request blood tests in some circumstances to prevent the development of muscle damage (rhabdomyolysis). In very severe cases, kidney failure may occur. If you experience severe muscle pain or weakness, contact your doctor immediately.
• You may experience difficulty breathing, irregular heartbeat, decreased urine production, sudden changes in mental status, skin patches, extremely low blood pressure associated with abnormal laboratory test results (decreased platelet count). If you experience any of the symptoms or signs indicated above, seek immediate medical attention.
• An abnormal accumulation of fluid in the lungs may occur, leading to swelling (pulmonary edema).
• You may notice partial or generalized swelling (edema) with possible dizziness, lightheadedness or thirst (low blood pressure). This may be a sign of a condition (capillary leak syndrome) that can cause excessive fluid accumulation in the tissues. If you experience any of the symptoms or signs indicated above seek immediate medical attention.
• Leakage of the Yondelis infusion solution from the vein (extravasation) may be noticed during the infusion of the medicine. In this case, you will notice redness, swelling, itching and discomfort at the injection site. If you experience any of these symptoms or signs, inform the nurse or doctor immediately.

This situation can lead to damage or death of the tissue cells surrounding the injection site (tissue necrosis), which may require surgery.
Some symptoms or signs of extravasation may not be visible until several hours after they occur. The skin at the injection site may develop blisters, peeling and dark coloration. It may take several days for the tissue damage to become fully visible. If you experience any of the symptoms or signs described above, seek immediate medical attention.

Rare: may affect up to 1 in 1,000 people

• You may experience yellowing of the skin and whites of the eyes (jaundice), pain in the upper right abdomen, nausea, vomiting, general feeling of unwellness, difficulty concentrating, disorientation or confusion, drowsiness. These signs may indicate that the liver is unable to function normally. If you experience any of the symptoms or signs described above, seek immediate medical attention.

Other less serious side effects

Very common: may affect more than 1 in 10 people

• You may: feel tired have difficulty breathing and cough have back pain experience an excess of fluid in the body (edema) have a tendency to develop bruises very easily bleed from the nose be more prone to infections. An infection may also lead to a temperature increase (fever). If you experience any of these symptoms, contact your doctor immediately.
• You may experience some symptoms related to digestion such as loss of appetite, nausea or vomiting, abdominal pain, diarrhea or constipation. If you still feel generally unwell, vomit or are unable to drink fluids with decreased urine production despite the administration of anti-nausea medications, contact your doctor immediately.
• Migraine may occur.
• Inflammation of the mucous membranes may occur in the form of redness with swelling inside the mouth with resulting painful ulcers and inflammation in the mouth (stomatitis) or inflammation of the gastrointestinal tract when Yondelis is administered with PLD.
• Patients taking Yondelis together with PLD for the treatment of ovarian cancer may also develop hand-foot syndrome. This can manifest as redness of the skin on the palms, fingers and soles of the feet, which may subsequently swell and turn purplish in color. The lesions may both dry and scale, and produce blisters with ulcerations.

Common: may affect up to 1 in 10 people

• Fluid loss from the body, weight loss, digestive disorders and changes in taste may occur.
• You may lose hair (alopecia).
• Dizziness, decreased blood pressure and flushing or rash may occur.
• Patients taking Yondelis together with PLD for ovarian cancer may experience more intense skin pigmentation.
• You may have joint pain.
• Sleep disturbances may occur.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Yondelis

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and on the label of the
vial. The expiry date refers to the last day of that month.
Store in a refrigerator (2 ºC – 8 ºC).
Information on the in-use stability of reconstituted and diluted solutions is included in the section for
physicians and healthcare professionals.
Do not use this medicine if you notice visible particles after reconstitution or dilution of the same.
Dispose of any unused product or waste material derived from this medicine in accordance with local legal
requirements.

6. Package contents and other information

What Yondelis contains

• The active ingredient is trabectedine. Yondelis 0.25 mg: Each powder vial contains 0.25 mg of trabectedine. Yondelis 1 mg: Each powder vial contains 1 mg of trabectedine.
• The other ingredients are sucrose, dipotassium hydrogen phosphate, phosphoric acid (for pH adjustment) and potassium hydroxide (for pH adjustment).

Description of Yondelis and package contents
Yondelis is a powder for concentrate for solution for infusion. The powder is from white to
off-white in color and is contained in a glass vial.
Each box contains 1 vial of 0.25 mg or 1 mg of trabectedine.

Marketing authorisation holder and manufacturer
Pharma Mar, S.A.
Avda. de los Reyes 1
Polígono Industrial La Mina
28770 Colmenar Viejo (Madrid)
Spain
Tel: +34 91 846 60 00
Fax: +34 91 846 60 01
For further information on this medicine, contact the marketing authorisation holder.

Other sources of information
More detailed information on this medicine is available on the website of the European
Medicines Agency, http://www.ema.europa.eu.
__________________________________________________________________________________
The following information is intended for healthcare professionals only:

Instructions for use, preparation, handling and disposal
Appropriate procedures must be followed for the correct handling and disposal of
cytotoxic medicines. Unused medicine and waste derived from this medicine must be
disposed of in accordance with local regulations for cytotoxic medicines.
Adequate training must be received on the correct techniques for reconstitution and dilution of
Yondelis or its combination with PLD, and protective clothing including mask, gloves and
glasses must be worn during reconstitution and dilution. Accidental contact with the skin, eyes
or mucous membranes must be treated immediately with plenty of water. Do not
handle this medicine if you are pregnant.
Preparation for intravenous infusion
Yondelis must be reconstituted and then diluted before infusion (see also section 3).

Appropriate aseptic techniques must be used.
Yondelis must not be administered mixed in the same infusion with other medicines other than
its diluent. No incompatibility of Yondelis with type I glass vials, with polyvinyl chloride (PVC) and
polyethylene (PE) bags and tubing, with polysoprene reservoirs and with implantable titanium
vascular access systems has been observed.
If Yondelis is used in combination with PLD, the intravenous infusion line must be flushed
thoroughly with 50 mg/mL (5%) glucose solution after PLD administration and before
Yondelis administration. The use of a diluent other than 50 mg/mL (5%) glucose solution may
cause PLD precipitation. (For specific instructions on handling, see also the PLD Summary of
Product Characteristics).

Instructions for reconstitution

Yondelis 0.25 mg:Inject 5 mL of sterile water for injections into the vial.

Yondelis 1 mg:Inject 20 mL of sterile water for injections into the vial.
Use a syringe to inject the correct amount of sterile water for injections into the
vial. Shake the vial until completely dissolved. The reconstituted solution is clear and
colorless or slightly yellowish, essentially free from visible particles.
This reconstituted solution contains 0.05 mg/mL of trabectedine. It requires further dilution and
is for single use only.

Instructions for dilution
Dilute the reconstituted solution with 9 mg/mL (0.9%) sodium chloride solution or 50 mg/mL (5%)
glucose solution for infusion. Calculate the volume required as follows:
Volume (mL) = BSA (m²) x individual dose (mg/m²)
0.05 mg/mL
BSA = Body Surface Area
Withdraw the appropriate amount of reconstituted solution from the vial. If intravenous
administration is to be carried out via a central venous line, the reconstituted solution must
be added to an infusion bag containing ≥ 50 mL of diluent (9 mg/mL (0.9%) sodium chloride
solution or 50 mg/mL (5%) glucose solution for infusion), with a concentration of
trabectedine in the infusion solution ≤ 0.030 mg/mL.
If central venous access is not feasible and a peripheral venous line must be used,
add the reconstituted solution to an infusion bag containing ≥ 1,000 mL of diluent
(9 mg/mL (0.9%) sodium chloride solution or 50 mg/mL (5%) glucose solution for infusion).
Before intravenous administration, visually inspect the parenteral solution for
the presence of particles. Once the infusion is prepared, administer it immediately.
Stability in use of solutions

Reconstituted solution
After reconstitution, chemical and physical stability has been demonstrated for 30 hours at up to 25 ºC.
From a microbiological point of view, the reconstituted solution must be diluted and used
immediately. Otherwise, the in-use storage times and conditions before use of the
reconstituted solution are the responsibility of the user and should not be longer
than 24 hours at 2°C - 8°C, unless the reconstitution has taken place under controlled and
validated aseptic conditions.

Diluted solution
After dilution, chemical and physical stability has been demonstrated for 30 hours at up to 25 ºC.