Prospecto:Information for the Patient

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

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

Read this prospectus carefully before starting to use this medication,because it contains important information for you.

• Keep this prospectus, as you may need to read it again.
• If you have any doubts, consult your doctor.
• If you experience adverse effects,consult your doctor,eveniftheydo not appear in this prospectus. See section 4.

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

2.What you need to knowbeforestarting touse Trabectedina Sun

3.How to use Trabectedina Sun

4.Possible adverse effects

5Storage of Trabectedina Sun

6.Contents of the package and additional information

Trabectedina Sunhas trabectedina as its active ingredient. Trabectedina is an anticancer medication that works by preventing the multiplication of tumor cells.

Trabectedina is used to treat patients with advanced soft tissue sarcoma, when previous treatment with other medications has not been effective or when patients cannot use other medications. Soft tissue sarcoma is a malignant neoplasm that begins in some soft tissues, such as muscles, fat, or other tissues (for example, cartilage or blood vessels).

Trabectedina in combination with pegylated liposomal doxorubicin (DLP, another antitumoral medication) is used to treat patients with ovarian cancer who have experienced a recurrence after at least 1 previous treatment and who are not resistant to anticancer medications containing platinum compounds.

No use Trabectedina Sun

• if you are allergic to trabectedina or any of the other components of this medication (listed in section 6);
• if you have a severe infection;
• if you are breastfeeding;
• if you are to be administered the yellow fever vaccine.

Warnings and Precautions

Consult your doctor before starting to use trabectedina.

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

Consult your doctor before starting treatment with trabectedina, 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.
• received high doses of anthracycline in the past.

Seek medical attention immediately if any of the following occur:

• if you have a fever, as trabectedina may cause side effects that affect the blood and liver.
• if, despite taking anti-vomiting medications, you experience nausea, vomiting, or are unable to drink liquids and, therefore, urinate less, seek medical attention immediately.
• if you experience intense muscle pain or weakness, as this could be a sign of muscle damage (rhabdomyolysis, see section 4).
• if you notice that the trabectedina infusion is leaking out of the vein during administration. This could damage or destroy the cells of the tissues near the injection site (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 feeling unwell (vomiting, see section 4).
• if you notice general or partial swelling without apparent cause (edema), possibly accompanied by dizziness, vertigo, or thirst (low blood pressure). This could be a manifestation of 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

Trabectedina must not be used in children under 18 years with pediatric sarcomas.

Other Medications and Trabectedina Sun

Inform your doctor if you are using, have used recently, or may need to use any other medication.

You must not use trabectedina if you are to be vaccinated against yellow fever and it is not recommended to use it if you are to be administered a vaccine containing live virus particles. It is not recommended to use medications containing phenytoin (for epilepsy treatment) with trabectedina, as the effect of phenytoin may be reduced.

If you use any of the following medications during your treatment with trabectedina, you need to be closely monitored, as the effects of trabectedina are:

• reduced (for example, using medications containing rifampicin (for bacterial infections), phenobarbital (for epilepsy), or St. John's Wort (Hypericum perforatum, a medicinal plant used for depression treatment)) or
• increased (for example, medications containing ketoconazole or fluconazole (for fungal infections), ritonavir (for HIV infection), clarithromycin (for bacterial infections), aprepitant (to prevent nausea and vomiting), cyclosporine (inhibit the body's defense system), or verapamil (for hypertension and other heart conditions)).

The use of trabectedina with any of these medications should be avoided if possible.

If, in addition to trabectedina or the combination of trabectedina and DLP, you are being administered another medication that can cause liver or muscle damage (rhabdomyolysis), you may be closely monitored, as this could increase the risk of liver or muscle damage. Medications containing statins (to reduce cholesterol levels and prevent cardiovascular diseases) are an example of medications that can cause muscle damage.

Use of Trabectedina Sun with Alcohol

Alcohol consumption should be avoided during treatment with trabectedina, as it can damage the liver.

Pregnancy,Lactation, and Fertility

Pregnancy

Trabectedina must not be used during pregnancy. If you are pregnant, think you may be pregnant, or intend to become pregnant, consult your doctor before using this medication.

Women of childbearing age must use effective contraceptive methods during treatment with trabectedina and for 3 months after treatment is completed.

If you become pregnant, inform your doctor immediately; in addition, it is recommended that you receive genetic counseling, as trabectedina may cause genetic damage to the fetus.

Lactation

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

Fertility

Males of childbearing age must use effective contraceptive methods during treatment with trabectedina and for 5 months after treatment is completed.

Due to the risk of irreversible infertility, it is recommended that patients seek advice on the possibility of preserving their eggs or sperm before treatment.

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

Driving and Operating Machinery

You may feel tired and experience a loss of strength during treatment with trabectedina. Do not drive or use tools or machinery if you experience any of these side effects.

Trabectedina Sun contains Potassium

This medication contains potassium, less than 1 mmol (39 mg) per vial, which is essentially "potassium-free".

Trabectedina must be administered under the supervision of a doctor with experience in the use of chemotherapy. Its use should be limited to qualified oncologists and other specialized healthcare professionals in the administration of cytotoxic drugs.

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 closely monitor you and decide which dose of trabectedina is most suitable 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 after administration of 30 mg/m² of body surface area of DLP.

Before administration, trabectedina must be reconstituted and diluted for intravenous use. Each time you are administered trabectedina for the treatment of soft tissue sarcoma, you will need approximately 24 hours for the entire solution to pass into your blood. Treatment of ovarian cancer will last 3 hours.

To avoid irritation in the injection area, it is recommended that you be administered trabectedina 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 trabectedina and as needed during treatment.

You will receive an infusion every 3 weeks, although occasionally your doctor may recommend delaying the dose so that you receive the most suitable dose of trabectedina.

The total duration of treatment will depend on your progress and how you feel. Your doctor will tell you how long your treatment may last. If you have any other questions about the use of this medication, ask your doctor.

Like all medicines, this medicine or its combination with DLP may cause side effects, although not everyone will experience them.

If you are unsure about the following side effects from the list below, ask your doctor to explain them in more detail.

Severe side effects caused by treatment with trabectedin:

Frequent: may affect more than 1 in 10 people

• You may experience elevated levels of the yellow pigment bilirubin in the blood, which could cause jaundice (yellow pigmentation of the skin, mucous membranes, and eyes).

• Your doctor will ask you to have regular blood tests to detect any abnormalities in the blood.

Frequent: may affect up to 1 in 10 people

• You may have blood infections (septicemia) if your immune system is severely affected.If you notice fever, go to your doctor 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 extremities and a sensation of tingling in the skin.

• You may experience a reaction at the injection site. The infusion of trabectedin may leak out of the vein during administration and cause tissue damage and destruction near the injection site (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 discomfort (vomiting).

• When trabectedin is used with DLP, you may experience syncope or fainting. Additionally, you may notice that your heart beats too fast or too hard (palpitations), experience weakness in the ventricles, which are the main pumping chambers of the heart (left ventricular dysfunction), or a sudden blockage of a pulmonary artery (pulmonary embolism).

Less frequent: may affect up to 1 in 100 people

• You may experience intense muscle pain and pain, stiffness, and muscle weakness. You may also experience a darkening of the urine color. All of the above could be a sign of muscle damage (rhabdomyolysis).

• Your doctor may request blood tests in certain situations to prevent muscle damage (rhabdomyolysis). In some very serious cases, these muscle damages could lead to kidney failure.If you experience intense muscle pain or weakness, go to your doctor immediately.

• You may experience difficulty breathing, irregular heart rhythm, decreased urine output, sudden changes in mental state, skin mottling, very low blood pressure associated with abnormal laboratory results. If you experience any of these symptoms or signs,go to your doctor immediately.

• You may experience abnormal fluid accumulation in the lungs, which causes swelling (pulmonary edema).

• You may notice general or partial swelling without apparent cause (edema), possibly accompanied by dizziness, vertigo, or thirst (low blood pressure). This could be a manifestation of a disorder (capillary leak syndrome) that can cause excessive fluid accumulation in your tissues. If this happens,go to your doctor immediately.

• You may notice that the trabectedin infusion leaks out of your vein while it is being administered (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 lead to tissue damage and cell death around the injection site (tissue necrosis), which may require surgery.

Some of the symptoms or signs of extravasation may not be visible until several hours after it occurs. In the area, blisters, peeling, and darkening of the skin may appear. Before the extent of tissue damage becomes visible, it may take several days. If you experience any of these symptoms or signs,go to your doctor immediately.

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

• You may experience yellow discoloration of the skin and globe of the eye (jaundice), pain in the upper right abdomen, nausea, vomiting, general feeling of discomfort, difficulty concentrating, disorientation or confusion, drowsiness. These signs may be indicative of the liver's inability to perform its normal function. If you experience any of these symptoms or signs,go to your doctor immediately.

Other less severe side effects:

Frequent: may affect more than 1 in 10 people

• You may:
• • feel tired
  • experience difficulty breathing and coughing
  • notice back pain
  • have excess fluid in the body (edema)
  • develop bruises (hematomas) more easily
  • experience nasal bleeding
  • be more prone to infections. An infection could also cause fever.

If you experience any of these symptoms, go to your doctor immediately.

• You may also experience some digestive symptoms such as decreased appetite, nausea, vomiting, abdominal pain, diarrhea, or constipation.If you experience nausea despite taking anti-nausea medication, vomit, or are unable to drink liquids and therefore urinate less, go to your doctor immediately.

• You may experience headaches.

• You may experience mucosal inflammation, which presents as redness and swelling of the inside of the mouth that causes painful ulcers and sores (stomatitis), or as inflammation of the gastrointestinal tract, when trabectedin is used with DLP.

• Patients receiving trabectedin with DLP for ovarian cancer may also experience hand-foot syndrome. It presents as redness of the skin of the palms of the hands, fingers, and soles of the feet, which, over time, may swell and turn purple. The lesions may be dry and scaly or in the form of blisters with ulceration.

Frequent: may affect up to 1 in 10 people

• You may experience fluid loss, weight loss, digestive discomfort, and altered sense of taste.

• You may lose hair (alopecia).

• You may also experience dizziness, low blood pressure, and hot flashes or skin rash.

• You may experience more pronounced skin pigmentation in patients receiving trabectedin with DLP for ovarian cancer.

• You may notice joint pain.

• You may experience sleep disturbances.

Reporting side effects

If you experience any type of side effect, consult your doctor, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Vigilance of Medicines for Human Use:http://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keepthis medicationout of the sight and reach of children.

Do not usethis medicationafter the expiration date that appears onthe packaging and on the vial label after CAD or EXP. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2? and 8 ?).

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

Do not use this medication if you observe visible particles after reconstitution or dilution of the medication.

The disposal of unused medication and all materials that have been in contact with it will be carried out in accordance with local regulations for cytotoxic medications.

Composition of Trabectedina Sun

• The active ingredient is trabectedina.
• 1. Trabectedina Sun 0.25 mg: each vial of powder contains 0.25 mg of trabectedina.
  2. Trabectedina Sun 1 mg: each vial of powder contains 1 mg of trabectedina.
• The other components are sacarose, dihydrogen phosphate of potassium, phosphoric acid (to adjust the pH) and potassium hydroxide (to adjust the pH).

Appearance of the product and contents of the package

Trabectedina Sun is a powder for concentrate for solution for infusion. The powder has a white or off-white color and is presented in a glass vial.

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

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Sun Pharmaceutical Industries Europe B.V.,

Polarisavenue 87

2132JH Hoofddorp

Netherlands

Responsible for manufacturing

Sun Pharmaceutical Industries Europe B.V.,

Polarisavenue 87

2132JH Hoofddorp

Netherlands

Or

Terapia S.A.

Str. Fabricii nr. 124

400632, Cluj-Napoca

Romania

You can request more information about this medication by contacting the local representative of the holder of the marketing authorization:

Sun Pharma Laboratorios, S.L.

Rambla de Catalunya, 53-55

08007 – Barcelona

Spain

Phone: +34 93 342 78 90

This medication is authorized in the member states of the European Economic Area with the following names:

GermanyTrabectedin SUN 0.25 mg Powder for a concentrate for the preparation of an infusion solution

Trabectedin SUN 1 mg Powder for a concentrate for the preparation of an infusion solution

Austria Trabectedin SUN 0.25 mg Powder for a concentrate for the preparation of an infusion solution

Trabectedin SUN 1 mg Powder for a concentrate for the preparation of an infusion solution

BelgiumTrabectedine SUN 0.25 mg powder for concentrate for solution for infusion

Trabectedine SUN 1 mg powder for concentrate for solution for infusion

DenmarkTrabectedin SUN

FranceTRABECTEDINE SUN 0.25 mg, powder for solution to be diluted for infusion

TRABECTEDINE SUN 1 mg, powder for solution to be diluted for infusion

ItalyTrabectedina SUN

SpainTrabectedina SUN 0.25 mg powder for concentrate for solution for perfusion EFG

Trabectedina SUN 1 mg powder for concentrate for solution for perfusion EFG

SwedenTrabektedin SUN 0.25 mg powder for concentrate for infusion solution, solution

Trabektedin SUN 1 mg powder for concentrate for infusion solution, solution

Last review date of this prospectus:October 2022

Other sources of information

The detailed information about this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)} (http://www.aemps.gob.es/)

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This information is intended solely for healthcare professionals:

Instructions for use, preparation, handling and disposal

They must follow the correct procedures for proper handling and disposal of cytotoxic drugs. The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations for cytotoxic drugs.

The healthcare professional must have received training in the correct techniques for reconstitution and dilution of trabectedina or its combination with DLP, and during the reconstitution and dilution of the drug, they must wear protective clothing, including a mask, protective glasses and gloves. Accidental contact with the skin, eyes or mucous membranes should be treated immediately with a large amount of water. If you are pregnant, you should not work with this medication.

Preparation for intravenous infusion

Trabectedina Sun must be reconstituted and then diluted before infusion (see also section 3).

Appropriate aseptic techniques must be used.

Trabectedina Sun should not be administered mixed with other medications that are not the diluent, in the same infusion. No incompatibilities have been observed between trabectedina and type I glass vials, or with PVC and PE bags and tubes, or with polyisoprene reservoirs or titanium vascular access systems.

When trabectedina is used in combination with DLP, the intravenous route must be thoroughly washed with 50 mg/ml (5%) glucose solution for infusion after administration of DLP and before administration of trabectedina. The use for infusion of a diluent other than 50 mg/ml (5%) glucose solution may cause precipitation of DLP. (See also section 4.2 and the DLP technical sheet, which contains specific instructions for its handling.)

Instructions for reconstitution

Trabectedina Sun 0.25 mg:inject 5 ml of sterile water for injection into the vial.

Trabectedina Sun 1 mg:inject 20 ml of sterile water for injection into the vial.

A syringe should be used to inject the correct amount of sterile water for injection into the vial. Shake the vial until the drug is completely dissolved. The reconstituted solution is transparent, colorless or slightly yellowish, without visible particles.

The reconstituted solution has a concentration of 0.05 mg/ml of trabectedina. It requires further dilutions and is intended for single use.

Instructions for dilution

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

Volumen (ml) =SC (m2) x dose individual (mg/m2)

0.05 mg/ml

SC = body surface area

Extract the appropriate amount of reconstituted solution from the vial; if the intravenous infusion is to be administered through a central venous route, add the reconstituted solution to a perfusion bag that contains ≥ 50 ml of diluent (9 mg/ml (0.9%) sodium chloride solution for infusion or 50 mg/ml (5%) glucose solution for infusion), with a trabectedina concentration in the infusion solution ≤ 0.030 mg/ml.

If it is not possible to use a central venous route and a peripheral venous route must be used, the reconstituted solution must be added to a perfusion bag that contains ≥ 1,000 ml of diluent (9 mg/ml (0.9%) sodium chloride solution for infusion or 50 mg/ml (5%) glucose solution for infusion).

Before intravenous administration, a visual inspection of the parenteral solutions will be performed to detect the possible presence of particles. The prepared infusion solution must be administered immediately.

Stability of the solutions during use

Reconstituted solution

After reconstitution, a chemical and physical stability of 30 hours up to 25 °C has been demonstrated.

From a microbiological point of view, the reconstituted solution must be diluted and used immediately. If it is not diluted and used immediately, the useful times and conditions for conservation of the reconstituted solution before use will be the responsibility of the user, and normally should not exceed 24 hours at 2 °C-8 °C, unless the reconstitution was carried out in validated and controlled aseptic conditions.

Diluted solution

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