Trabectedin EG

Package leaflet: Information for the patient

Trabectedin EG 0.25 mg powder for concentrate for solution for infusion, 1 mg powder for concentrate for solution for infusion

Generic medicine
Please read all of this leaflet carefully before you are given this medicine because 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 experience any side effects, including any not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

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

1. What Trabectedin EG is and what it is used for

Trabectedin EG contains the active substance trabectedin. Trabectedin EG is an anticancer medicine that
prevents the multiplication of tumour cells.
Trabectedin EG is used to treat patients with advanced soft tissue sarcoma who have not benefited from, or
cannot receive, other medicines. Soft tissue sarcoma is a malignant disease that arises in any of the soft
tissues, such as muscle, fat, or other tissues (e.g. cartilage or blood vessels).
Trabectedin EG in combination with pegylated liposomal doxorubicin (PLD: another anticancer medicine) is
used to treat patients with recurrent (returned) ovarian cancer after at least one prior therapy, and who are not
resistant to platinum-containing anticancer medicines.

2. What you need to know before you are given Trabectedin EG

Do not use Trabectedin EG

• if you are allergic to trabectedin or to 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 receive the yellow fever vaccine.

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

• 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 therapy

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

• If you have a fever, as Trabectedin EG may cause side effects affecting the blood and liver.
• If you have general malaise, vomiting or are unable to drink fluids, accompanied by reduced urine output despite 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 Trabectedin EG solution from the vein during infusion. This may cause tissue damage and destruction around the injection site (tissue necrosis, see also section 4), which might require surgical intervention.
• If you experience an allergic reaction (hypersensitivity). In such a case, you may develop one or more of the following signs: fever, difficulty breathing, skin redness, flushing or skin rash, feeling unwell (nausea), or illness (vomiting; see section 4).
• If you develop partial or generalized swelling (edema), possibly accompanied by confusion, dizziness or thirst (low blood pressure). This could be a sign of a condition (capillary leak syndrome) that may cause excessive fluid accumulation in tissues and requires urgent medical evaluation.

Children and adolescents
Trabectedin EG must not be used in children under 18 years of age with pediatric sarcomas.
Other medicines and Trabectedin EG
Tell your doctor if you are taking, have recently taken, or might take any other medicines.
You must not use Trabectedin EG if you are due to receive the yellow fever vaccine, and the use of Trabectedin EG 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 when given together with Trabectedin EG, and therefore their concomitant use is not recommended.
If you are taking any of the following medicines during treatment with Trabectedin EG, close monitoring is required, as the effects of Trabectedin EG may be:

• reduced (some examples include medicines containing rifampicin (for bacterial infections), phenobarbital (for epilepsy), or St. John’s wort (Hypericum perforatum, a herbal remedy for depression)), or
• increased (some examples include medicines containing ketoconazole or fluconazole (for fungal infections), ritonavir (for HIV infections, human immunodeficiency virus), clarithromycin (for bacterial infections), aprepitant (to prevent nausea and vomiting), cyclosporine (to suppress the body’s immune system), or verapamil (for high blood pressure and heart conditions)).
  Therefore, the use of any of these medicines with Trabectedin EG should be avoided, if possible.
  If you have been prescribed Trabectedin EG or the combination Trabectedin EG + PLD together with a medicine that may cause liver damage or muscle damage (rhabdomyolysis), careful monitoring may be necessary, as there may be an increased risk of liver or muscle injury. Medicines containing statins (to lower cholesterol levels and prevent cardiovascular disease) are an example of medicines that may cause muscle injury.
  Trabectedin EG and alcohol
  Avoid drinking alcohol during treatment with Trabectedin EG, as it may damage the liver.
  Pregnancy, breastfeeding and fertility
  Pregnancy
  Trabectedin EG must not be used during pregnancy. If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, consult your doctor before receiving this medicine.
  Women of childbearing potential must use effective contraception during treatment with Trabectedin EG and for 8 months after treatment ends.
  If you become pregnant, inform your doctor immediately. Genetic counselling is recommended, as Trabectedin EG may cause genetic damage.
  Breastfeeding
  Trabectedin EG must not be administered to patients who are breastfeeding. Therefore, you must stop breastfeeding before starting treatment and must not resume breastfeeding until your doctor confirms that there is no risk.
  Fertility
  Men of reproductive potential must use effective contraception during treatment with Trabectedin EG and for 5 months after treatment ends.
  Consider preserving oocytes or sperm before treatment due to the possibility of irreversible infertility caused by Trabectedin EG therapy.
  Genetic counselling is recommended for all patients wishing to have children after therapy.
  Driving and using machines
  During treatment with Trabectedin EG, you may experience fatigue and loss of strength. Do not drive or operate tools or machinery if you experience these side effects.
  Trabectedin EG contains sodium
  This medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e. essentially ‘sodium-free’.

3. How to use Trabectedin EG

Trabectedin EG must be administered under the supervision of a physician experienced in the use of chemotherapy. Its use should be restricted to qualified oncologists or other healthcare professionals specialized in the administration of cytotoxic agents.

For the treatment of soft tissue sarcoma, the usual dose is 1.5 mg/m² of body surface area. During the treatment period, your doctor will monitor you closely and determine the most appropriate dose of Trabectedin EG for you. The recommended dose for Japanese patients is lower than the standard dose used in all other populations and is 1.2 mg/m² of body surface area.

For the treatment of ovarian cancer, the usual dose is 1.1 mg/m² of body surface area, administered after pegylated liposomal doxorubicin (PLD) at a dose of 30 mg/m² of body surface area.

Before administration, Trabectedin EG must be reconstituted and diluted for intravenous use. Each time Trabectedin EG is administered for the treatment of soft tissue sarcoma, it will take approximately 24 hours to complete the infusion into the bloodstream. For ovarian cancer treatment, the infusion will take 3 hours.

To avoid potential irritation at the injection site, administration of Trabectedin EG through a central venous line is recommended.

You will be given a medicinal product before treatment and, if necessary, during treatment with Trabectedin EG, to protect the liver and reduce the risk of undesirable effects such as nausea and vomiting.

The infusion is repeated every 3 weeks, although occasionally your doctor may recommend delaying administration to ensure you receive the appropriate dose of Trabectedin EG.

The total duration of treatment will depend on disease progression and your overall health status. Your doctor will decide how long the treatment should continue. If you have any doubts about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine, or its combination with PLD, may cause side effects,
although not everybody experiences them.
If you have any doubts about the side effects listed below, please consult your doctor for a more
detailed explanation.

Serious side effects caused by treatment with trabectedin:

Very common: may affect more than 1 in 10 people

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

Common: may affect up to 1 in 10 people

• You may develop blood infections (sepsis) if your immune system is severely weakened. If you develop a fever, inform your doctor immediately.
• You may also experience muscle pain (myalgia). Nerve damage may occur, causing muscle pain, weakness, and tenderness. General swelling, limb swelling, and a sensation of chills on the skin may also occur.
• A reaction at the injection site may occur. The infusion solution containing trabectedin may leak out of the vein during administration, causing damage and destruction of surrounding tissue cells (tissue necrosis; see also section 2 “Warnings and precautions”), which may require surgical intervention.
• You may have an allergic reaction. In this case, you may experience fever, difficulty breathing, skin redness, flushing or rash, a feeling of illness (nausea), or general malaise (vomiting).
• When trabectedin is used in combination with PLD, fainting (syncope) 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 chambers responsible 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 dark-colored urine. All of the effects described above may be signs of muscle damage (rhabdomyolysis).
• Your doctor may request blood tests in certain 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, reduced urine output, sudden changes in mental status, skin patches, extremely low blood pressure associated with abnormal laboratory results (reduced platelet count). If you experience any of the symptoms or signs listed above, seek immediate medical attention.
• You may develop an abnormal accumulation of fluid in the lungs, causing swelling (pulmonary edema).
• You may notice unexplained partial or generalized swelling (edema), possibly accompanied by dizziness, lightheadedness, or thirst (low blood pressure). This could be a sign of a condition (capillary leak syndrome) that causes excessive fluid buildup in tissues. If you experience any of the symptoms or signs listed above, seek immediate medical attention.
• Leakage of the Trabectedin EG infusion solution from the vein (extravasation) may occur during infusion. 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 your nurse or doctor immediately.

This situation may lead to damage or death of cells in the tissue surrounding the injection site
(tissue necrosis), which may require surgical intervention.
Some symptoms or signs of extravasation may not become visible until several hours after they occur.
The skin at the injection site may develop blisters, peeling, and dark discoloration. It may take several days
for tissue damage to become fully apparent. 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 part of the abdomen, nausea, vomiting, general malaise, difficulty concentrating, disorientation, or confusion, and drowsiness. These signs may indicate that the liver is unable to function properly. If you experience any of the symptoms or signs listed above, seek immediate medical attention.

Other less severe side effects:
Very common: may affect more than 1 in 10 people

• You may:
  • feel tired
  • have difficulty breathing and cough
  • have back pain
  • feel excess fluid in the body (edema)
  • have a tendency to develop bruises very easily
  • have nosebleeds
  • be more prone to infections. An infection may also lead to an increase in body temperature (fever). If you experience any of these symptoms, contact your doctor immediately.
• You may experience digestive symptoms such as loss of appetite, nausea or vomiting, abdominal pain, diarrhea, or constipation. If you continue to feel unwell, vomit, or are unable to drink fluids with reduced urine output despite anti-nausea medication, contact your doctor immediately.
• Headache may occur.
• You may develop inflammation of mucous membranes, presenting as redness and swelling inside the mouth, leading to painful ulcers and inflammation in the mouth (stomatitis), or inflammation of the gastrointestinal tract when trabectedin is administered with PLD.
• Female patients receiving trabectedin together with PLD for ovarian cancer may also develop hand-foot syndrome. This may present as skin redness on the palms, fingers, and soles of the feet, which may later swell and turn purple. The lesions may either dry out and peel or form blisters with ulceration.

Common: may affect up to 1 in 10 people

• Fluid loss from the body, weight loss, digestive disturbances, and changes in taste may occur.
• You may lose your hair (alopecia).
• Dizziness, low blood pressure, flushing, or skin rash may also occur.
• Female patients receiving trabectedin with PLD for ovarian cancer may develop increased skin pigmentation.
• You may have joint pain.
• Sleep disturbances may occur.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your
doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Trabectedina EG

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack and on the label of the vial after the word EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C - 8°C).
Information on the 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.
Unused medicine or waste material must be disposed of in accordance with local regulations governing cytotoxic medicinal products.

6. Package contents and other information

What Trabectedina EG contains

• The active substance is trabectedin. Trabectedina EG 0.25 mg: each vial of powder contains 0.25 mg of trabectedin. Trabectedina EG 1 mg: each vial of powder contains 1 mg of trabectedin.
• The other components are mannitol, monohydrate citric acid, sodium citrate.

Description of the appearance of Trabectedina EG and contents of the pack
Trabectedina EG is a powder for concentrate for solution for infusion. The powder is white to off-white in colour and is contained in a glass vial.
Each carton contains 1 vial of 0.25 mg or 1 mg of trabectedin.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
EG S.p.A., Via Pavia 6, 20136 Milano, Italy

Manufacturers
Prestige Promotion Verkaufsförderung und Werbeservice GmbH, Borsigstrasse 2, 63755 Alzenau – Germany
STADA Arzneimittel GmbH, Muthgasse 36/2, 1190 Wien – Austria
STADA Arzneimittel AG, Stadastrasse 2 - 18, 61118 Bad Vilbel – Germany
Laboratori Fundació Dau, Calle Lletra C de la Zona Franca 12-14, Polígono Industrial de la Zona Franca de Barcelona, 08040 Barcelona – Spain

This medicinal product is authorised in the European Economic Area Member States under the following names:
AT Trabectedin STADA 0.25 mg powder for a concentrate for solution for infusion
Trabectedin STADA 1 mg powder for a concentrate for solution for infusion
BE Trabectedin EG 0.25 mg powder for concentrate for solution for infusion
Trabectedin EG 1 mg powder for concentrate for solution for infusion
DE Trabectedin STADA 0.25 mg powder for a concentrate for solution for infusion
Trabectedin STADA 1 mg powder for a concentrate for solution for infusion
ES Trabectedina 0.25 mg powder for concentrate for perfusion solution EFG
Trabectedina 1 mg powder for concentrate for perfusion solution EFG
FI Trabectedin STADA 0.25 mg dry substance for intermediate concentrate for infusion solution, solution
Trabectedin STADA 1 mg dry substance for intermediate concentrate for infusion solution, solution
FR TRABECTEDINE EG 0.25 mg, powder for solution to be diluted for perfusion
TRABECTEDINE EG 1 mg, powder for solution to be diluted for perfusion
HU Trabectedin Stada 0.25 mg powder for concentrate for infusion
Trabectedin Stada 1 mg powder for concentrate for infusion
IT Trabectedina EG
LU Trabectedin EG 0.25 mg powder for solution to be diluted for perfusion
Trabectedin EG 1 mg powder for solution to be diluted for perfusion
NO Trabectedin STADA 0.25 mg powder for concentrate for infusion solution, solution
Trabectedin STADA 1 mg powder for concentrate for infusion solution, solution
RO Trabectedină Stada 0.25 mg powder for concentrate for perfusion solution
Trabectedină Stada 1 mg powder for concentrate for perfusion solution
SE Trabectedin STADA 0.25 mg powder for concentrate for infusion solution, solution
Trabectedin STADA 1 mg powder for concentrate for infusion solution, solution

The following information is intended exclusively for physicians or healthcare professionals:

Instructions for use – preparation, handling and disposal
Follow procedures for proper handling and disposal of cytotoxic medicinal products. Unused medicine or waste material must be disposed of in accordance with local regulations governing cytotoxic medicinal products.
Appropriate training in the correct reconstitution and dilution techniques of Trabectedina EG or its combination with PLD must be received, and protective clothing including mask, gloves and goggles must be worn during reconstitution and dilution. Accidental contact with skin, eyes or mucous membranes must be immediately rinsed with copious amounts of water. This medicine must not be handled during pregnancy.

Preparation of intravenous infusion
Trabectedina EG must be reconstituted and then diluted prior to infusion (see also section 3).
Appropriate aseptic techniques must be used.
Trabectedina EG must not be administered mixed in the same infusion with other medicinal products except the diluent. No incompatibility of trabectedin has been observed with type I glass vials, bags and tubing made of polyvinylchloride (PVC) and polyethylene (PE), polysoprene reservoirs, or titanium implantable vascular access systems.
If Trabectedina EG is used in combination with PLD, thoroughly flush the intravenous administration line with glucose 50 mg/ml (5%) solution for infusion after administration of PLD and before administering Trabectedina EG. Use of a diluent other than glucose 50 mg/ml (5%) solution for infusion may cause precipitation of PLD. (For specific handling instructions, see also the Summary of Product Characteristics of PLD.)

Instructions for reconstitution
Trabectedina EG 0.25 mg: Inject 5 ml of sterile water for injection into the vial.
Trabectedina EG 1 mg: Inject 20 ml of sterile water for injection into the vial.
Use a syringe to inject the correct volume of sterile water for injection into the vial. The vial should be gently agitated until complete dissolution is achieved. The reconstituted solution is clear and colourless or slightly yellowish, essentially free from visible particles.
This reconstituted solution contains 0.05 mg/ml of trabectedin. Further dilution is required. This solution is for single use only.

Instructions for dilution
Dilute the reconstituted solution with sodium chloride 9 mg/ml (0.9%) solution or glucose 50 mg/ml (5%) solution for infusion. Calculate the required volume as follows:
Volume (ml) = BSA (m²) × individual dose (mg/m²)