Trabectedin STADA 0.25 mg powder for concentrate for solution for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Trabectedina Stada 0.25 mg powder for concentrate for solution for infusion EFG

Trabectedina Stada 1 mg powder for concentrate for solution for infusion EFG

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet as you may need to read it again.
• If you have any questions, consult your doctor.
• If you experience any adverse reactions, consult your doctor, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

1. What Trabectedina Stada is and what it is used for
2. What you need to know before using Trabectedina Stada
3. How to use Trabectedina Stada
4. Possible adverse reactions
5. How to store Trabectedina Stada
6. Contents of the pack and other information

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

This medicine contains trabectedin as the active substance. Trabectedin is an anticancer medicine that works by preventing the multiplication of tumour cells.

Trabectedin is used to treat patients with advanced soft tissue sarcoma when prior treatment with other medicines has not worked or when patients cannot be treated with other medicines. Soft tissue sarcoma is a malignant neoplasm that originates in soft tissues such as muscles, fat, or other tissues (e.g., cartilage or blood vessels).

Trabectedin in combination with pegylated liposomal doxorubicin (PLD, another antitumour medicine) is used to treat patients with ovarian cancer who have relapsed after at least one prior treatment and who are not platinum-resistant.

2. What you need to know before starting to use Trabectedin Stada

Do not use Trabectedin Stada

• 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 scheduled to receive the yellow fever vaccine.

Warnings and precautions

Talk to your doctor before starting to use this medicine.

You must not use trabectedin or its combination with PLD if you have severe liver, kidney, or heart problems.

Consult your doctor before starting treatment with trabectedin if you know or suspect that you have:

• Liver or kidney problems.
• Heart problems or a history of heart problems.
• A left ventricular ejection fraction (LVEF) below the lower limit of normal.
• Have previously received treatment with high doses of anthracyclines.

Seek immediate medical attention if any of the following conditions occur:

• If you develop fever, as trabectedin may cause side effects affecting the blood and liver.
• If, despite taking anti-nausea medication, you experience nausea, vomiting, or are unable to drink fluids and therefore urinate less, contact your doctor immediately.
• If you experience severe muscle pain or weakness, as this could be a sign of muscle damage (rhabdomyolysis; see section 4).
• If you notice leakage of the trabectedin infusion from the vein during administration. This could damage or destroy cells in nearby tissues (tissue necrosis; see also section 4), which may require surgical intervention.
• If you have an allergic reaction (hypersensitivity). In this case, you may experience one or more of the following symptoms: fever, difficulty breathing, redness or flushing of the skin or rash, dizziness (nausea), or general malaise (vomiting; see section 4).
• If you notice generalized or localized swelling without apparent cause (edema), possibly accompanied by dizziness, vertigo, or thirst (low blood pressure). This could indicate a disorder (capillary leak syndrome) that may cause excessive fluid accumulation in your tissues and requires urgent clinical evaluation by your doctor.

Children and adolescents

Trabectedin must not be used in children under 18 years of age with pediatric sarcomas.

Other medicines and Trabectedin Stada

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines.

You must not use trabectedin if you are to be vaccinated against yellow fever. The use of trabectedin is also not recommended if you are to receive a vaccine containing live virus particles. The use of medications containing phenytoin (for the treatment of epilepsy) together with trabectedin is not recommended, as the effect of phenytoin may be reduced.

If you are taking any of the following medicines during your treatment with trabectedin, you need to be closely monitored, as they may alter the effects of trabectedin:

• Reduced (e.g., medicines containing rifampicin (for bacterial infections), phenobarbital (for epilepsy), or St. John’s wort (Hypericum perforatum, a herbal remedy used for the treatment of depression)), or
• Increased (e.g., medicines containing ketoconazole or fluconazole (for fungal infections), ritonavir (for human immunodeficiency virus [HIV] infection), clarithromycin (for bacterial infections), aprepitant (to prevent nausea and vomiting), cyclosporine (immunosuppressants), or verapamil (for hypertension and other heart conditions)).

The use of trabectedin together with any of these medicines should be avoided if possible.

If you are receiving another medicine capable of causing liver or muscle damage (rhabdomyolysis) at the same time as trabectedin or the combination of trabectedin and PLD, you may require close monitoring, as this could increase the risk of liver or muscle injury. Medicines containing statins (used to reduce cholesterol levels and prevent cardiovascular disease) are an example of medicines that may cause muscle damage.

Use of Trabectedin Stada with alcohol

Alcohol consumption should be avoided during treatment with trabectedin, as it may cause liver damage.

Pregnancy, breastfeeding and fertility

Pregnancy

Trabectedin must not be used during pregnancy. If you are pregnant, think you might be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Women of childbearing potential must use effective contraceptive methods during treatment with trabectedin and for up to 8 months after completion of treatment.

If you become pregnant, you must inform your doctor immediately; genetic counselling is also recommended, as trabectedin may cause genetic damage to the fetus.

Breastfeeding

Trabectedin must not be administered to patients who are breastfeeding. Therefore, before starting treatment, you must stop breastfeeding and must not resume it until your doctor confirms it is safe to do so.

Fertility

Men of reproductive age must use effective contraceptive methods during treatment with trabectedin and for up to 5 months after treatment.

As there is a risk that treatment with trabectedin may cause irreversible infertility, patients are advised to seek counselling regarding the possibility of preserving their eggs or sperm before treatment.

Genetic counselling is also recommended for patients who wish to have children after treatment.

Driving and operating machinery

You may feel tired and notice loss of strength during treatment with trabectedin. Do not drive or operate tools or machines if you experience any of these side effects.

Trabectedin Stada contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per vial; this is, essentially "sodium-free".

3. How to use Trabectedin Stada

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

For the treatment of soft tissue sarcoma, the normal 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 for you. The recommended dose in Japanese patients is lower than the usual dose for other races 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 following administration of 30 mg/m² of body surface area of DLP.

Before administration, trabectedin must be reconstituted and diluted for intravenous use. Each time trabectedin is administered for the treatment of soft tissue sarcoma, it will take approximately 24 hours for the entire solution to infuse into your bloodstream. Ovarian cancer treatment will last 3 hours.

To avoid irritation at the injection site, it is recommended that trabectedin be administered through a central venous line.

To protect the liver and reduce the risk of adverse effects such as nausea and vomiting, you will be given other medications before treatment with trabectedin and whenever needed during treatment.

You will receive an infusion every 3 weeks, although occasionally your doctor may recommend delaying doses to ensure you receive the most appropriate dose of trabectedin.

The total duration of treatment will depend on your response and how you feel. Your doctor will inform you how long your treatment may last. If you have any further questions about the use of this medicine, ask your doctor.

4. Possible adverse effects

Like all medicines, this medicine or its combination with DLP may cause adverse effects, although not everyone experiences them.

If you are unsure about what the following list describes, please ask your doctor to explain it in more detail.

Serious adverse effects caused by treatment with trabectedin:

Very common: may affect more than 1 in 10 people

• You may have elevated levels of the yellow pigment bilirubin in the blood, which could lead to jaundice (yellowing of the skin, mucous membranes, and eyes).
• Your doctor will regularly request 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 compromised. If you develop fever, seek medical attention immediately.
• You may also experience muscle pain (myalgia). You may also suffer nerve damage, which causes muscle pain, weakness, and numbness. You may experience general swelling or swelling of the limbs and a tingling sensation on the skin.
• You may have a reaction at the injection site. Trabectedin infusion may leak out of the vein during administration, causing injury and destruction of cells in nearby tissues (tissue necrosis; see also section 2 “Warnings and precautions”), which may require surgical intervention.
• You may experience an allergic reaction. In this case, you may have fever, difficulty breathing, redness or flushing of the skin or rash, general discomfort (nausea), or a feeling of malaise (vomiting).
• When trabectedin is used together with DLP, you may experience fainting or collapse. Additionally, you may notice your heart beating too hard or too fast (palpitations), weakness in the ventricles—the main pumping chambers of the heart (left ventricular dysfunction), or sudden blockage of a pulmonary artery (pulmonary embolism).

Uncommon: may affect up to 1 in 100 people

• You may experience severe muscle pain and discomfort, muscle stiffness, and weakness. You may also notice darkening of the urine. All of the above could be signs of muscle damage (rhabdomyolysis).
• Your doctor may request blood tests in certain situations to prevent muscle damage (rhabdomyolysis). In very severe cases, such muscle damage could lead to kidney failure. If you experience severe muscle pain or weakness, seek medical attention immediately.
• You may experience difficulty breathing, irregular heartbeat, reduced urine output, sudden changes in mental status, mottled skin areas, very low blood pressure associated with abnormal laboratory results (decreased platelet count). If you experience any of these symptoms or signs, seek medical attention immediately.
• You may develop abnormal fluid accumulation in the lungs, leading to swelling (pulmonary edema).
• You may notice general or localized swelling without apparent cause (edema), possibly accompanied by dizziness, vertigo, or thirst (low blood pressure). This could indicate a disorder (capillary leak syndrome) that causes excessive fluid accumulation in your tissues. If this occurs, seek medical attention immediately.
• You may notice that the trabectedin infusion is leaking out of your vein during administration (extravasation). Therefore, you may notice redness, swelling, itching, and discomfort at the injection site. If you experience any of these symptoms or signs, inform your doctor or nurse immediately.

This could result in damage and death of surrounding tissue cells at the injection site (tissue necrosis), which may require surgery.

Some symptoms or signs of extravasation may not become visible until several hours after it occurred. Blisters, peeling, and skin discoloration may appear at the site. Several days may pass before the extent of tissue damage becomes apparent. If you experience any of these symptoms or signs, seek medical attention immediately.

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, drowsiness. These signs may indicate the liver's inability to perform its normal function. If you experience any of these symptoms or signs, seek medical attention immediately.

Other less severe adverse effects:

Very common: may affect more than 1 in 10 people

• You may:
  • feel tired
  • experience difficulty breathing and cough
  • feel back pain
  • retain excess fluid in the body (edema)
  • develop bruises (bruising) more easily
  • have nosebleeds
  • be more prone to infections. An infection may also cause fever
  • (fever).

If you experience any of these symptoms, seek medical attention immediately.

• You may also experience gastrointestinal symptoms such as decreased appetite, nausea or vomiting, abdominal pain, diarrhea, or constipation. If you continue to have nausea, vomit, or are unable to drink fluids despite taking anti-nausea medication, and therefore urinate less, seek medical attention immediately.
• You may experience headache.
• You may develop mucosal inflammation, appearing as redness and swelling inside the mouth leading to painful ulcers and sores (stomatitis), or as gastrointestinal tract inflammation when trabectedin is used together with DLP.
• Female patients receiving trabectedin together with DLP for ovarian cancer may also develop hand-foot syndrome. This presents as redness of the skin on the palms of the hands, fingers, and soles of the feet, which over time may swell and turn purplish. The lesions may be dry and scaly or appear as blisters with ulceration.

Common: may affect up to 1 in 10 people

• You may experience fluid loss, weight loss, gastrointestinal discomfort, and altered sense of taste.
• You may lose hair (alopecia).
• You may also experience dizziness, low blood pressure, hot flashes, or skin rash.
• Increased skin pigmentation may occur in patients receiving trabectedin together with DLP for ovarian cancer.
• You may feel joint pain.
• You may experience sleep disturbances.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Trabectedin

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the carton and on the label of the vial after EXP. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (2 °C - 8 °C).

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

Do not use this medicine if visible particles are observed after reconstitution or dilution of the medicine.

Disposal of unused medicine and of all materials that have been in contact with it must be carried out in accordance with local regulations for cytotoxic medicinal products.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the container and other information

Composition of Trabectedin Stada

• The active substance is trabectedin.

Trabectedin Stada 0.25 mg: each vial of powder contains 0.25 mg of trabectedin.

Trabectedin Stada 1 mg: each vial of powder contains 1 mg of trabectedin.

• The other components are mannitol, monohydrate citric acid, sodium citrate.

Appearance of the product and contents of the container

Trabectedin Stada is a powder for concentrate for solution for infusion. The powder is white to off-white and is supplied in a glass vial.

Each package contains 1 vial of 0.25 mg or 1 vial of 1 mg of trabectedin.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Laboratorio STADA, S.L.

Frederic Mompou, 5

08960 Sant Just Desvern (Barcelona)

Spain

[email protected]

Manufacturer

Prestige Promotion Verkaufsförderung und Werbeservice GmbH

Borsigstrasse 2

63755 Alzenau

Germany

or

STADA Arzneimittel GmbH

Muthgasse 36/2

1190 Wien

Austria

or

STADA Arzneimittel AG

Stadastrasse 2 - 18

61118 Bad Vilbel

Germany

or

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 authorized in the Member States of the European Economic Area under the following names:

Austria	Trabectedin STADA 0.25 mg powder for concentrate for solution for infusion Trabectedin STADA 1 mg powder for concentrate for solution for infusion
Belgium	Trabectedin EG 0.25 mg powder for concentrate for solution for infusion Trabectedin EG 1 mg powder for concentrate for solution for infusion
Germany	Trabectedin STADA 0.25 mg powder for concentrate for solution for infusion Trabectedin STADA 1 mg powder for concentrate for solution for infusion
Spain	Trabectedina Stada 0.25 mg powder for concentrate for perfusion solution EFG Trabectedina Stada 1 mg powder for concentrate for perfusion solution EFG
Finland	Trabectedin STADA 0.25 mg powder for concentrate for infusion solution, solution Trabectedin STADA 1 mg powder for concentrate for infusion solution, solution
France	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
Hungary	Trabectedin Stada 0.25 mg powder for concentrate for infusion solution Trabectedin Stada 1 mg powder for concentrate for infusion solution
Italy	Trabectedina EG
Luxembourg	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
Norway	Trabectedin STADA 0.25 mg powder for concentrate for infusion solution, solution Trabectedin STADA 1 mg powder for concentrate for infusion solution, solution
Romania	Trabectedina Stada 0.25 mg powder for concentrate for perfusion solution Trabectedina Stada 1 mg powder for concentrate for perfusion solution
Sweden	Trabectedin STADA 0.25 mg powder for concentrate for infusion solution, solution Trabectedin STADA 1 mg powder for concentrate for infusion solution, solution

Date of the most recent review of this leaflet: February 2026

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).

This information is intended for healthcare professionals only:

Instructions for use, preparation, handling, and disposal

Appropriate procedures must be followed for the proper handling and disposal of cytotoxic medicinal products. Disposal of unused medicinal product and all materials that have come into contact with it must be carried out in accordance with local regulations for cytotoxic medicinal products.

Healthcare professionals must have received training in the correct techniques for reconstitution and dilution of trabectedin or its combination with DLP, and must wear protective clothing, including mask, protective goggles, and gloves during reconstitution and dilution of the drug. Accidental contact with skin, eyes, or mucous membranes must be immediately rinsed with abundant water. If you are pregnant, you should not handle this medicinal product.

Preparation for intravenous infusion

Trabectedin must be reconstituted and subsequently diluted prior to infusion (see also section 3).

Aseptic techniques must be used.

Trabectedin must not be administered mixed with other medicinal products except the diluent in the same infusion. No incompatibilities have been observed between trabectedin and type I glass vials, poly(vinyl chloride) (PVC) and polyethylene (PE) bags and tubing, polyisoprene reservoirs, or titanium implantable vascular access systems.

When trabectedin is used in combination with DLP, the intravenous line must be thoroughly flushed with 50 mg/ml (5 %) glucose solution for infusion after administration of DLP and before administration of trabectedin. The use of any diluent other than 50 mg/ml (5 %) glucose solution for infusion may cause precipitation of DLP. (See also the summary of product characteristics of DLP, which contains specific instructions for its handling.)

Instructions for reconstitution

Trabectedin 0.25 mg: Inject 5 ml of sterile water for injections into the vial.

Trabectedin 1 mg: Inject 20 ml of sterile water for injections into the vial.

A syringe should be used to inject the correct volume of sterile water for injections into the vial. Shake the vial until the drug is completely dissolved. The reconstituted solution is clear, colourless or slightly yellowish, and free from visible particles.

The reconstituted solution has a concentration of 0.05 mg/ml of trabectedin. Further dilution is required, and the solution is intended for single use only.

Instructions for dilution

Dilute the reconstituted solution with either 9 mg/ml (0.9 %) sodium chloride solution for infusion or 50 mg/ml (5 %) glucose solution for infusion. Calculate the required volume as follows:

SC = body surface area

Withdraw the appropriate volume of reconstituted solution from the vial; if intravenous administration is to be performed via a central venous line, add the reconstituted solution to an infusion bag containing ≥ 50 ml of diluent (either 9 mg/ml (0.9 %) sodium chloride solution for infusion or 50 mg/ml (5 %) glucose solution for infusion), resulting in a trabectedin concentration in the infusion solution ≤ 0.030 mg/ml.

If a central venous line cannot be used and a peripheral venous line must be used instead, the reconstituted solution must be added to an infusion bag containing ≥ 1,000 ml of diluent (either 9 mg/ml (0.9 %) sodium chloride solution for infusion or 50 mg/ml (5 %) glucose solution for infusion).

Prior to intravenous administration, parenteral solutions should be inspected visually for particulate matter. Once the infusion is prepared, it should be administered immediately.

Stability during use

Reconstituted solution

After reconstitution, chemical and physical stability has been demonstrated for 30 hours at up to 25 °C, or for up to 21 days if stored between 2 °C and 8 °C.

From a microbiological standpoint, the reconstituted solution should be diluted and used immediately. If not diluted and used immediately, the in-use storage times and conditions prior to use of the reconstituted solution are the responsibility of the user and should normally not exceed 24 hours at 2 °C – 8 °C, unless reconstitution was carried out under validated and controlled aseptic conditions.

Diluted solution

After dilution, chemical and physical stability has been demonstrated for 30 hours at up to 25 °C.