Trabectedin Ever Pharma

Leaflet attached to the packaging: patient information

Trabectedin EVER PHARMA, 0.25 mg, powder for concentrate for solution for infusion

for infusion

Trabectedin EVER PHARMA, 1 mg, powder for concentrate for solution for infusion

Trabectedinum

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should inform their doctor. See section 4.

Table of contents of the leaflet

• 1. What is Trabectedin and what is it used for
• 2. Important information before using Trabectedin
• 3. How to use Trabectedin
• 4. Possible side effects
• 5. How to store Trabectedin
• 6. Package contents and other information

1. What is Trabectedin and what is it used for

Trabectedin contains the active substance trabectedin. Trabectedin is an anticancer medicine that works by preventing the growth of cancer cells. Trabectedin is used to treat patients with advanced soft tissue sarcoma, if previous treatments have been ineffective or the patient is not eligible for them. Soft tissue sarcoma is a malignant disease that starts in soft tissue, such as muscle tissue, fat, or other tissues (e.g., cartilage or blood vessels). Trabectedin in combination with pegylated liposomal doxorubicin (PLD, another anticancer medicine) is used to treat patients with ovarian cancer that has recurred after at least one previous therapy and is not resistant to anticancer medicines containing platinum compounds.

2. Important information before using Trabectedin

When not to use Trabectedin

Warnings and precautions

Before starting treatment with Trabectedin, the patient should discuss it with their doctor. Trabectedin, alone or in combination with PLD, should not be used in patients with severe liver, kidney, or heart damage. Before starting treatment with Trabectedin, the patient should tell their doctor about any existing or suspected:

• Liver or kidney function disorders.
• Heart function disorders, currently or in the past.
• Left ventricular ejection fraction (LVEF) below the lower limit of normal.
• Prior treatment with high-dose anthracyclines.

The patient should immediately consult their doctor if they experience any of the following conditions:

• If the patient has a fever, as Trabectedin may cause side effects that affect the blood or liver.
• If the patient experiences nausea, vomiting, or inability to take fluids, resulting in decreased urine output despite the use of antiemetic drugs.
• If the patient experiences severe muscle pain or weakness, which may be a sign of muscle damage (rhabdomyolysis; see section 4).
• If the patient experiences leakage of the Trabectedin solution outside the vein during infusion. This can cause tissue damage and necrosis at the injection site (tissue necrosis, see also section 4) and may require surgical intervention.
• If the patient experiences an allergic reaction (hypersensitivity). In this case, the patient may experience one or more of the following symptoms: fever, respiratory problems, skin redness or flushing, or rash, nausea, or vomiting (see section 4).
• If the patient experiences localized or generalized edema of unknown cause, with possible accompanying feelings of emptiness in the head, dizziness, or desire (low blood pressure). This may be a sign of capillary leak syndrome, which can cause excessive fluid accumulation in tissues and requires immediate medical evaluation by a doctor.

Children and adolescents

Trabectedin should not be used in children under 18 years of age with diagnosed soft tissue sarcoma.

Trabectedin and other medicines

The patient should tell their doctor about all medicines they are currently taking or plan to take. Trabectedin should not be used if the patient is receiving a yellow fever vaccine, and it is not recommended to use Trabectedin if the patient is to receive a live virus vaccine. The effect of the medicine containing phenytoin (an antiepileptic drug) may be reduced if Trabectedin is used at the same time, and such use is not recommended. If the patient is taking any of the following medicines during treatment with Trabectedin, close monitoring may be necessary, as the effect of Trabectedin may be:

• reduced [e.g., medicines containing rifampicin (for bacterial infections), phenobarbital (an antiepileptic drug), or St. John's wort (Hypericum perforatum, a herbal medicine used to treat depression)] or
• increased [e.g., medicines containing ketoconazole or fluconazole (for fungal infections), ritonavir (for HIV infection), clarithromycin (for bacterial infections), aprepitant (to prevent nausea and vomiting), cyclosporine (to suppress the immune system), or verapamil (for hypertension and heart disease)].

If possible, the patient should avoid taking Trabectedin with any of these medicines. If the patient is receiving Trabectedin alone or in combination with PLD, along with a medicine that can damage the liver or muscles (rhabdomyolysis), close monitoring may be necessary, as there is a higher risk of liver or muscle damage. Medicines containing statins (to lower cholesterol and prevent cardiovascular disease) are an example of medicines that can cause muscle damage.

Using Trabectedin with alcohol

The patient should not drink alcohol during treatment with Trabectedin, due to the risk of liver damage.

Pregnancy, breastfeeding, and fertility

Pregnancy Trabectedin should not be used during pregnancy. If the patient is pregnant, thinks they may be pregnant, or plans to have a child, they should consult their doctor before using this medicine. Women of childbearing age must use effective contraception during and for 3 months after treatment with Trabectedin. If the patient becomes pregnant, they should immediately inform their doctor and genetic counseling is recommended, as Trabectedin may cause genetic changes. Breastfeeding Trabectedin should not be given to breastfeeding women. Therefore, breastfeeding should be stopped before starting treatment and not resumed until the doctor considers it safe. Fertility Men of childbearing age must use effective contraception during and for 5 months after treatment with Trabectedin. Patients should consult their doctor about sperm or egg preservation before starting treatment, due to the risk of irreversible infertility caused by Trabectedin. Genetic counseling is also recommended for patients planning to have children after treatment.

Driving and using machines

During treatment with Trabectedin, the patient may feel tired and weak. If the patient experiences such symptoms, they should not drive or operate machines.

Trabectedin contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per vial, which means it is essentially "sodium-free".

3. How to use Trabectedin

Trabectedin is administered only under the supervision of a doctor with experience in the use of chemotherapy. The use of the medicine should be limited to qualified oncologists or other healthcare professionals specialized in the administration of cytotoxic drugs. In the treatment of soft tissue sarcoma, the typical dose is 1.5 mg/m2 of body surface area. During treatment, the patient will be closely monitored, and the doctor will determine the most suitable dose for the patient. The recommended dose for Japanese patients is lower than the typical dose for patients of all other races and is 1.2 mg/m2. In the treatment of ovarian cancer, the typical dose is 1.1 mg/m2 of body surface area, after prior administration of PLD at a dose of 30 mg/m2 of body surface area. Trabectedin is dissolved and diluted before intravenous administration. Each administration of Trabectedin in the treatment of soft tissue sarcoma takes approximately 24 hours, allowing the entire solution to be introduced into the patient's body. In the treatment of ovarian cancer, the administration takes 3 hours. To avoid irritation at the injection site, it is recommended to administer Trabectedin through a catheter inserted into a central vein. Before administration and if necessary during administration of Trabectedin, the patient will receive a medicine to protect the liver and reduce the risk of side effects, such as nausea and vomiting. The infusion is administered every 3 weeks, but it may be recommended to delay doses to ensure that the administered dose of Trabectedin is the most suitable. The duration of the entire treatment period depends on the patient's progress and well-being. The doctor will inform the patient about the duration of treatment. If the patient has any further doubts about the use of this medicine, they should consult their doctor.

4. Possible side effects

Like all medicines, Trabectedin, alone or in combination with PLD, can cause side effects, although not everybody gets them. If the patient has any doubts about the following side effects, they should consult their doctor for a detailed explanation. Severe side effects caused by Trabectedin Very common: may occur more often than 1 in 10 people

• The patient may experience an increase in bilirubin levels in the blood, which can cause jaundice (yellowing of the skin, mucous membranes, and eyes).
• The doctor will recommend regular blood tests to detect any abnormalities in the blood.

Common: may occur no more often than 1 in 10 people

• If the patient has a significantly weakened immune system, they may develop a blood infection (sepsis). If the patient has a fever, they should immediately consult their doctor.
• The patient may also experience muscle pain. Additionally, muscle damage may occur, causing muscle pain, weakness, and numbness. Generalized edema or swelling of the limbs and a feeling of suffering on the skin may occur.
• Reactions at the injection site may occur. The Trabectedin solution may leak out of the vein during infusion, leading to tissue damage and necrosis at the injection site (tissue necrosis, see also section 2 "Warnings and precautions") and may require surgical intervention.
• The patient may experience an allergic reaction. In this case, the patient may experience one or more of the following symptoms: fever, respiratory problems, skin redness or flushing, or rash, nausea, or vomiting.
• If Trabectedin is used in combination with PLD, the patient may experience fainting. Additionally, the patient may experience an abnormally fast or strong heartbeat (palpitations), weakened heart function (left ventricular dysfunction), or sudden blockage of a pulmonary artery (pulmonary embolism).

Uncommon: may occur no more often than 1 in 100 people

• The patient may experience severe muscle pain, stiffness, and weakness. The urine may become darker. All the above symptoms may indicate muscle damage (rhabdomyolysis).
• In certain situations, the doctor may order blood tests to prevent muscle damage (rhabdomyolysis). In very severe cases, this can lead to kidney failure. If the patient experiences severe pain or weakness, they should immediately consult their doctor.
• The patient may experience respiratory problems, heart rhythm disorders, decreased urine output, sudden changes in mental state, patchy skin, extremely low blood pressure, accompanied by abnormal laboratory test results (decreased platelet count). If the patient experiences any of the above symptoms or signs, they should immediately consult their doctor.
• The patient may experience abnormal fluid accumulation in the lungs, leading to edema (pulmonary edema).
• The patient may experience localized or generalized edema of unknown cause, with possible accompanying feelings of emptiness in the head, dizziness, or desire (low blood pressure). This may be a sign of capillary leak syndrome, which can cause excessive fluid accumulation in tissues and requires immediate medical evaluation by a doctor.

Other, less serious, side effects Very common: may occur more often than 1 in 10 people

• The patient may experience:
• fatigue
• breathing difficulties or coughing
• back pain
• a feeling of excess fluid in the body (edema)
• increased bruising
• nosebleeds
• increased susceptibility to infections; infection can also cause a high body temperature (fever). If the patient experiences any of these symptoms, they should immediately consult their doctor.
• Additionally, the patient may experience gastrointestinal symptoms such as loss of appetite, nausea, or vomiting, abdominal pain, diarrhea, or constipation. If the patient experiences nausea, vomiting, or inability to take fluids, resulting in decreased urine output despite the use of antiemetic drugs, they should immediately consult their doctor for help.
• The patient may experience headaches.
• The patient may experience mouth sores, which can appear as swollen, red, and painful ulcers, or as inflammation of the digestive tract, especially when Trabectedin is used in combination with PLD.
• Women receiving Trabectedin in combination with PLD for ovarian cancer may experience hand-foot syndrome, which appears as redness of the hands, fingers, and soles of the feet, and may later become swollen and discolored.

Affected areas may dry out, peel, or form blisters and ulcers. Common: may occur no more often than 1 in 10 people

• The patient may experience dehydration, weight loss, digestive problems, and changes in taste.
• The patient may experience hair loss (alopecia).
• The patient may feel dizzy, have low blood pressure, and experience sudden flushing of the face or skin rash.
• Women receiving Trabectedin in combination with PLD for ovarian cancer may experience excessive skin pigmentation.
• The patient may experience joint pain.
• The patient may experience sleep disturbances.

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in this leaflet, they should inform their doctor. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181 C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: + 48 22 49 21 309, website: https://smz.ezdrowie.gov.pl Side effects can also be reported to the marketing authorization holder. By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Trabectedin

The medicine should be stored out of sight and reach of children. Do not use this medicine after the expiry date stated on the carton and vial label after "Expiry Date (EXP)". The expiry date refers to the last day of the month stated. Store in a refrigerator (2°C - 8°C). Information on the stability of the solution after reconstitution and dilution is provided in the section intended for healthcare professionals. Do not use this medicine if you notice any solid particles after reconstitution or dilution. All unused medicine or waste materials should be disposed of in accordance with local regulations on cytotoxic medicines.

6. Package contents and other information

What Trabectedin contains

• The active substance of the medicine is trabectedin. Trabectedin 0.25 mg: One vial of powder contains 0.25 mg of trabectedin. Trabectedin 1 mg: One vial of powder contains 1 mg of trabectedin.
• The other ingredients are: citric acid, arginine, phosphoric acid, concentrated (to adjust pH), and sodium hydroxide (to adjust pH).

What Trabectedin looks like and what the pack contains

Trabectedin is a powder for concentrate for solution for infusion. The powder is white or almost white and is contained in a glass vial. The glass vial containing 0.25 mg of trabectedin is closed with a rubber stopper and a light blue aluminum flip-off seal. The glass vial containing 1 mg of trabectedin is closed with a rubber stopper and a pink aluminum flip-off seal. Each carton contains 1 vial of 0.25 mg or 1 mg of trabectedin. The vials may, but do not have to be, protected with a protective sleeve.

Marketing authorization holder

EVER Valinject GmbH Oberburgau 3 4866 Unterach am Attersee Austria

Manufacturer

EVER Pharma Jena GmbH Otto-Schott-Straße 15 07745 Jena Germany EVER Pharma Jena GmbH Brüsseler Straße 18 07747 Jena Germany