ТРABEKTЕДИНА 0.25 мг Порошок для концентрата для инфузионного раствора

Содержание инструкции

1. Trabectedina Accord 0.25 mg powder for concentrate for solution for infusion, 1 mg powder for concentrate for solution for infusion.
   1. What is Trabectedina Accord and what is it used for
   2. What you need to know before using Trabectedina Accord
   3. How to use Trabectedina Accord
   4. Possible side effects
   5. How to store Trabectedina Accord
   6. Package Contents and Other Information

Trabectedina Accord 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 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 any side effects occur, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

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

1. What is Trabectedina Accord and what is it used for

Trabectedina Accord contains the active substance trabectedine. Trabectedina Accord is an antitumoral medicine that prevents the multiplication of tumor cells.
Trabectedina Accord 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).
Trabectedina Accord associated with pegylated liposomal doxorubicin (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 using Trabectedina Accord

Do not use Trabectedina Accord

• if you are allergic to trabectedine 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 Trabectedina Accord.
Trabectedina Accord, 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 Trabectedina Accord:
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 Trabectedina Accord can cause side effects that
also affect the blood and liver.
If you feel unwell, vomit or are unable to drink fluids with reduced urine output
despite the administration of anti-nausea medication.
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 Trabectedina Accord solution from the vein during the infusion of the
medicine. This can cause damage and destruction of the cells of the tissues around the injection site
(tissue necrosis, see also section 4) which may require surgical removal of 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
skin rash, feeling unwell (nausea) or feeling sick (vomiting; see
section 4).
If you notice partial or generalized swelling (edema) with possible dizziness,
vertigo or thirst (low blood pressure). This could 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
Trabectedina Accord should not be used in children under 18 years of age with pediatric sarcomas.

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

immunodeficiency virus,HIV), clarithromycin (for bacterial infections), aprepitant (for
preventing 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 Trabectedina Accord should be avoided, if
possible.
If you have been prescribed Trabectedina Accord or Trabectedina Accord + 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 capable of causing muscle injury.

Trabectedina Accord with alcohol
Avoid drinking alcohol during treatment with Trabectedina Accord as this could
damage the liver.

Pregnancy, breastfeeding and fertility
Pregnancy
Trabectedina Accord should not be used during pregnancy. If you are pregnant, suspect or
are planning a pregnancy, ask your doctor for advice before taking this medicine.
Women of childbearing potential must use effective contraceptive methods during
the administration of Trabectedina Accord and for 3 months after treatment.
In case of pregnancy, inform your doctor immediately and genetic counseling is recommended
because Trabectedina Accord can cause genetic damage.
Breastfeeding
Trabectedina Accord 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 should use effective contraceptive methods during treatment with
Trabectedina Accord and for 5 months after treatment.
Patients are advised to consider the preservation of eggs and sperm before
treatment due to the risk of irreversible infertility due to therapy with Trabectedina Accord.
Genetic counseling is also recommended for all patients who wish to have a child
after therapy.

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

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

3. How to use Trabectedina Accord

Trabectedina Accord 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
Trabectedina Accord most appropriate to administer to you. 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 area
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 Trabectedina Accord, it is reconstituted and diluted for infusion
for intravenous use. Each time you are administered Trabectedina Accord 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
Trabectedina Accord through a central venous line.
You will be given some medications, before treatment with Trabectedina Accord 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 postponing the administration to
ensure that you receive the appropriate dose of Trabectedina
Accord.
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 Trabectedina Accord:

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).
• The 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 solution for infusion with Trabectedina Accord may leak from the vein during administration of the medicine, causing damage and destruction of the cells of the tissues around the site of

injection (tissue necrosis, see also section 2 “Warnings and precautions”) which may
require surgical intervention 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 Trabectedina Accord 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 the effects described above may be a sign of muscle damage (rhabdomyolysis).
• The doctor may require blood tests in some circumstances to avoid 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 Trabectedina Accord 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 cells of the tissue surrounding the
injection site (tissue necrosis), which may require surgical intervention.
Some symptoms or signs of extravasation may not be visible until several hours after
they have occurred. The skin at the injection site may develop blisters,
peeling and dark discoloration. It may take several days before the tissue damage is
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 an increase in temperature (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 medicines contact your doctor immediately.
• You may experience migraine.
• You may experience inflammation of the mucous membranes in the form of redness with swelling inside the mouth leading to painful ulcers and inflammation of the gastrointestinal tract when Trabectedina Accord is administered with PLD.
• Patients taking Trabectedina Accord together with PLD for the treatment of ovarian cancer may also develop hand-foot syndrome. This may manifest with redness of the skin on the palms, fingers and soles of the feet, which may subsequently swell and become purplish in color. The lesions may both dry and peel, 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 the sense of taste may occur.
• You may lose hair (alopecia).
• Dizziness, decreased blood pressure and flushing or rash may occur.
• Patients taking Trabectedina Accord 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, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet. You can also report side effects directly through the national reporting system reported in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Trabectedina Accord

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 package 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 derived from this in accordance with local legal requirements.

6. Package Contents and Other Information

What Trabectedina Accord Contains

• The active ingredient is trabectedine. Trabectedina Accord 0.25 mg: Each powder vial contains 0.25 mg of trabectedine. Trabectedina Accord 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 Trabectedina Accord and Package Contents
Trabectedina Accord is a powder for concentrate for solution for infusion. The powder is
from white to off-white in colour and is contained in a glass vial.
Each pack contains 1 vial of either 0.25 mg or 1 mg of trabectedine.

Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona, s/n
Edifici Est, 6a Planta
08039 Barcelona
Spain

Manufacturers
Accord Healthcare Polska Sp.z.o.o.
Ul. Lutomierska 50,
95-200, Pabianice, Poland
Or
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park,
Paola, PLA3000, Malta
Or
Accord Healthcare Single Member S.A.
64th Km National Road Athens, Lamia, 32009, Greece
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:
AT / BE / BG / CY / CZ / DE / DK / EE / ES / FI / FR / HR / HU / IE / IS / IT / LT / LV / LU / MT /
NL / NO / PL / PT / RO / SE / SI / SK
Accord Healthcare S.L.U.
Tel: +34 93 301 00 64
EL
Win Medica Α.Ε.
Τηλ: +30 210 74 88 821

Other Sources of Information
More detailed information on this medicinal product is available on the website of the European
Medicines Agency, https://www.ema.europa.eu.
__________________________________________________________________________________
The following information is intended exclusively for healthcare professionals:

Instructions for Use, Preparation, Handling and Disposal
Appropriate procedures must be followed for the correct handling and disposal of
cytotoxic medicinal products. Unused medicinal product and waste materials derived from such
medicinal product must be disposed of in accordance with current local regulations for cytotoxic
medicinal products.
Adequate training must be received on the correct techniques for reconstitution and dilution of
Trabectedina Accord or its combination with PLD, and protective clothing including mask, gloves
and goggles 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
medicinal product if you are pregnant.
Preparation for intravenous infusion
Trabectedina Accord must be reconstituted and then diluted before infusion (see also
section 3). Appropriate aseptic techniques must be used.
Trabectedina Accord must not be administered mixed in the same infusion with other
medicinal products other than its diluent. No incompatibility of Trabectedina Accord 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.
When using Trabectedina Accord in combination with PLD, the intravenous infusion line must be
carefully flushed with 50 mg/mL (5%) glucose solution after PLD administration and before
Trabectedina Accord 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 Summary
of Product Characteristics of PLD).

Instructions for Reconstitution

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

Trabectedina Accord 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
colourless 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 required volume 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 has been prepared, administer it immediately.
Stability in use of solutions

Reconstituted solution
Chemical and physical stability has been demonstrated for 30 hours at 20 °C to 25 ºC and from 2 °C to 8 °C.
From a microbiological point of view, the reconstituted solution must be diluted and used
immediately. Otherwise, the storage times and conditions in use of the reconstituted solution are the
responsibility of the user and should not be longer than 24 hours at 2 °C to 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 up to 25 ºC.
From a microbiological point of view, unless the opening/reconstitution/dilution process
prevents the risk of microbial contamination, the product must be used immediately. Otherwise, the
user is responsible for the storage times and conditions in use.