Trabectedin Accord 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 Accord 0.25 mg powder for concentrate for solution for infusion.

Trabectedina Accord 1 mg powder for concentrate for solution for infusion.

trabectedin

Read all of this 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, ask your doctor.
• If you experience any side effects, consult your doctor, even if they are side effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Trabectedina Accord is and what it is 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. Contents of the pack and other information

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

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

Trabectedin Accord is used to treat patients with advanced soft tissue sarcoma when previous treatment with other medicines has not been effective or when patients cannot use 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 Accord 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 to anticancer medicines containing platinum compounds.

2. What you need to know before using Trabectedin Accord

Do not use Trabectedin Accord

• 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 due to receive the yellow fever vaccine.

Warnings and precautions

Talk to your doctor before starting treatment with Trabectedin Accord.

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

Talk to your doctor before starting treatment with Trabectedin Accord if you know or suspect 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 occur:

• If you develop fever, as Trabectedin Accord can 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, seek immediate medical attention.
• 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 Accord 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, skin redness or rash, feeling dizzy (nausea), or feeling unwell (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 Accord must not be used in children under 18 years of age with pediatric sarcomas.

Other medicines and Trabectedin Accord

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

Do not use Trabectedin Accord if you are due to receive the yellow fever vaccine. It is also not recommended to use Trabectedin Accord if you are to receive a vaccine containing live virus particles. The use of medicines containing phenytoin (for treatment of epilepsy) is not recommended with Trabectedin Accord, as the effect of phenytoin may be reduced.

If you are taking any of the following medicines during treatment with Trabectedin Accord, close monitoring is required because the effects of Trabectedin Accord may be:

• Reduced (e.g., medicines containing rifampicin (for bacterial infections), phenobarbital (for epilepsy), or St. John’s wort (Hypericum perforatum, a herbal remedy used for 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 (to suppress the body’s immune system), or verapamil (for hypertension and other heart conditions)).

The use of Trabectedin Accord with any of these medicines should be avoided if possible.

If you are receiving another medicine alongside Trabectedin Accord or the combination of Trabectedin Accord and DLP that can cause liver damage or muscle damage (rhabdomyolysis), you may require close monitoring, as this could increase the risk of liver or muscle injury. Medicines containing statins (used to lower cholesterol levels and prevent cardiovascular disease) are an example of medicines that can cause muscle damage.

Use of Trabectedin Accord with alcohol

Alcohol consumption should be avoided during treatment with Trabectedin Accord, as it may damage the liver.

Pregnancy, breastfeeding, and fertility

Pregnancy

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

Women of childbearing potential must use effective contraception during treatment with Trabectedin Accord and for up to 3 months after completion of treatment.

If you become pregnant, inform your doctor immediately; genetic counseling is also recommended, as Trabectedin Accord may cause genetic damage to the fetus.

Breastfeeding

Trabectedin Accord 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 potential must use effective contraception during treatment with Trabectedin Accord and for up to 5 months after treatment.

Because there is a risk that treatment with Trabectedin Accord may cause irreversible infertility, patients are advised to seek counseling on the possibility of preserving eggs or sperm before starting treatment.

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

Driving and use of machines

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

Trabectedin Accord contains potassium

This medicine contains less than 1 mmol (39 mg) of potassium per vial; therefore, it is essentially “potassium-free”.

3. How to use Trabectedin Accord

Trabectedin Accord 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 decide which dose of Trabectedin Accord is most appropriate 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, Trabectedin Accord must be reconstituted and diluted for intravenous use. Each time you are given Trabectedin Accord for the treatment of soft tissue sarcoma, it will take approximately 24 hours for the entire solution to be infused into your bloodstream. Ovarian cancer treatment will last 3 hours.

To avoid irritation at the injection site, it is recommended that Trabectedin Accord 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 Accord 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 Accord.

The total duration of treatment will depend on your progress 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 PLD may cause adverse effects, although not everyone will experience them.

If you are unsure about any of the following effects listed below, please ask your doctor to explain them in more detail.

Serious adverse effects caused by treatment with Trabectedin Accord:

Very common: may affect more than 1 in 10 people

• You may have elevated levels of the yellow pigment bilirubin in your blood, which could lead to jaundice (yellowing of the skin, mucous membranes, and eyes).
• Your doctor will regularly request blood tests to detect any abnormalities in your blood.

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 skin tingling sensations.
• You may experience a reaction at the injection site. Trabectedin Accord 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 develop fever, difficulty breathing, redness or flushing of the skin or rash, general malaise (nausea), or feeling unwell (vomiting).
• When Trabectedin Accord is used together with PLD, you may experience fainting or collapse. In addition, you may notice your heart beating too hard or too fast (palpitations), weakness in the ventricles, which are the heart's main pumping chambers (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 muscle pain, stiffness, and weakness. You may also notice darkening of the urine color. 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, this 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, which in turn causes 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 be a manifestation of a disorder (capillary leak syndrome) that may cause excessive fluid accumulation in your tissues. If this occurs, seek medical attention immediately.
• You may notice that the Trabectedin Accord 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 lead to tissue damage and cell death around 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 full extent of tissue damage becomes visible. 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 the 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 functions. If you experience any of these symptoms or signs, seek medical attention immediately.

Other less serious adverse effects:

Very common: may affect more than 1 in 10 people

• You may:
• feel tired
• experience difficulty breathing and cough
• feel back pain
• have excess fluid in the body (edema)
• develop bruises (hematomas) more easily
• have nosebleeds
• be more prone to infections. An infection may also cause 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 have nausea, vomit, or are unable to drink fluids despite taking anti-vomiting medication, and therefore urinate less, seek medical attention immediately.

• You may experience headache.

• You may develop mucositis, which presents as redness and swelling of the lining of the mouth leading to painful ulcers and sores (stomatitis), or as inflammation of the gastrointestinal tract when Trabectedin Accord is used together with PLD.

• Female patients receiving Trabectedin Accord together with PLD 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 may later swell and turn purplish. The lesions may be dry and peeling 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 taste sensation.
• 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 Accord together with PLD 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, talk to your doctor, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Trabectedin Accord

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 is the last day of the month indicated.

Store in a refrigerator (2 °C to 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 come into contact with it must be carried out in accordance with local regulations for cytotoxic medicines.

6. Package contents and other information

Composition of Trabectedin Accord

• The active substance is trabectedin.

Trabectedin Accord 0.25 mg: each vial of powder contains 0.25 mg of trabectedin.
Trabectedin Accord 1 mg: each vial of powder contains 1 mg of trabectedin.

• The other components are sucrose, potassium dihydrogen phosphate, phosphoric acid (to adjust pH), and potassium hydroxide (to adjust pH).

Appearance of the medicinal product and contents of the pack of Trabectedin Accord

Trabectedin Accord is a powder for concentrate for solution for infusion. The powder is white or almost white and is presented in a glass vial.

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

Marketing Authorisation Holder and Manufacturer

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

Further information about this medicinal product is available upon request to 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.
Tel: +30 210 74 88 821

Date of the most recent revision of this leaflet:

Other sources of information

Detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu/.

This information is intended for healthcare professionals only:

Instructions for use, preparation, handling, and disposal

Appropriate procedures for the safe handling and disposal of cytotoxic medicinal products must be followed. Disposal of unused medicinal product and of 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 Accord or its combination with DLP. During reconstitution and dilution of the medicinal product, protective clothing including mask, safety goggles, and gloves must be worn. If you are pregnant, you must not handle this medicinal product.

Preparation for intravenous infusion

Trabectedin Accord must be reconstituted and subsequently diluted before infusion (see also section 3). Appropriate aseptic techniques must be used.

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

When Trabectedin Accord 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 Accord. Using a 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 Accord 0.25 mg: Inject 5 ml of sterile water for injections into the vial.
Trabectedin Accord 1 mg: Inject 20 ml of sterile water for injections into the vial.

A syringe must be used to inject the correct amount 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. It requires further dilution and 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:

Volume (ml) = BSA (m²) × individual dose (mg/m²)