BENDAMUSTINE 2.5 mg/ml Powder

Contents of the leaflet

1. Package Leaflet: Information for the User
2. Bendamustine Eugia, 2.5 mg/ml, powder for concentrate for solution for infusion
   1. Read all of this leaflet carefully before taking this medicine because it contains important information for you.
   2. Contents of the pack and other information:
3. What Bendamustine Eugia is and what it is used for
4. Before you take Bendamustine Eugia
   1. When not to take Bendamustine Eugia:
   2. Warnings and precautions
   3. Bendamustine Eugia and other medicines
   4. Pregnancy, breastfeeding, and fertility
   5. Pregnancy
   6. Breastfeeding
   7. Fertility
   8. Driving and using machines
5. How to take Bendamustine Eugia
   1. Chronic lymphocytic leukemia
   2. Non-Hodgkin's lymphoma
   3. Multiple myeloma
   4. Impaired liver or kidney function
   5. How the medicine is given
   6. Duration of treatment
   7. Missing a dose of Bendamustine Eugia
   8. Stopping treatment with Bendamustine Eugia
6. Possible side effects
   1. Very common:
   2. Common:
   3. Uncommon:
   4. Rare:
   5. Very rare:
   6. Frequency not known:
   7. Reporting side effects
7. How to store Bendamustine Eugia
8. Contents of the pack and other information
   1. What Bendamustine Eugia contains
   2. What Bendamustine Eugia looks like and contents of the pack
   3. Marketing authorization holder and manufacturer
   4. Marketing authorization holder:
   5. Manufacturer/Importer:
   6. This medicine is authorized in the Member States of the European Economic Area under the following names:
   7. Date of last revision of the leaflet: 03/2024
   8. Information intended for healthcare professionals only:

Package Leaflet: Information for the User

Bendamustine Eugia, 2.5 mg/ml, powder for concentrate for solution for infusion

Bendamustine hydrochloride

Read all of this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information:

• 1. What Bendamustine Eugia is and what it is used for
• 2. Before you take Bendamustine Eugia
• 3. How to take Bendamustine Eugia
• 4. Possible side effects
• 5. How to store Bendamustine Eugia
• 6. Contents of the pack and other information

1. What Bendamustine Eugia is and what it is used for

Bendamustine Eugia is a medicine used to treat certain types of cancer (cytotoxic medicine).
Bendamustine Eugia is used alone (monotherapy) or in combination with other medicines to treat the following types of cancer:

• Chronic lymphocytic leukemia when the patient is not a candidate for combination chemotherapy that includes fludarabine,
• Non-Hodgkin's lymphoma that has not responded or has responded poorly to previous treatment with rituximab,
• Multiple myeloma when treatment that includes thalidomide or bortezomib is not suitable for the patient.

2. Before you take Bendamustine Eugia

When not to take Bendamustine Eugia:

• If you are allergic to bendamustine hydrochloride or any of the other ingredients of this medicine (listed in section 6);
• During breastfeeding; if treatment with Bendamustine Eugia is necessary during lactation, breastfeeding must be discontinued (see "Pregnancy, breastfeeding, and fertility");
• If you have severe liver damage (damage to liver cells);
• If you have jaundice (yellowing of the skin or whites of the eyes) due to liver or blood disorders;
• If you have severe bone marrow depression (reduction in blood cell production) and significant changes in white blood cell and platelet counts;

and/or

• If you have had major surgery within 30 days before starting treatment;
• If you have an infection, especially with a low white blood cell count (leukopenia);
• If you have been vaccinated against yellow fever.

Warnings and precautions

Before taking Bendamustine Eugia, discuss with your doctor, pharmacist, or nurse:

• if you have reduced bone marrow function. Before starting treatment with Bendamustine Eugia and before each subsequent treatment cycle, as well as between treatment cycles, your white blood cell and platelet counts should be checked.
• if you have an infection. Contact your doctor if you experience symptoms of infection, including fever and respiratory symptoms.
• if you experience skin reactionsduring treatment with Bendamustine Eugia. These reactions can worsen.
• if you experience a painful, red, or purple spreading rash with blisters and/or other mucosal changes (e.g., in the mouth and on the lips), especially if you have previously experienced sensitivity to light, respiratory infection (e.g., bronchitis), and/or fever.
• if you have pre-existing heart disease (e.g., heart attack, chest pain, severe heart rhythm disturbances).
• if you experience pain in your side, blood in your urine, or decreased urine output. In advanced cancer, the body may not be able to remove all the waste products from dying cancer cells. This condition is called tumor lysis syndrome and can lead to kidney failure and heart problems within 48 hours of the first dose of Bendamustine Eugia. Your doctor should ensure that you are well-hydrated and can receive other medicines to prevent this condition.
• if you experience severe allergic reactions or hypersensitivity reactions. Pay attention to symptoms related to infusion reactions after the first treatment cycle.
• you should immediately tell your doctor if you experience any of the following symptoms at any time during or after treatment: memory loss, thinking problems, difficulty walking, or vision loss - these may be caused by a very rare but serious brain infection (progressive multifocal leukoencephalopathy, PML), which can be fatal.
• if you notice any suspicious skin changes, you should contact your doctor, due to the increased risk of certain types of skin cancer when using this medicine (non-melanoma skin cancer).

Bendamustine Eugia and other medicines

Tell your doctor or pharmacist about all medicines you are taking or have recently taken, as well as any medicines you plan to take.
If Bendamustine Eugia is used in combination with other medicines that suppress blood cell production in the bone marrow, its effect on the bone marrow may be increased.
If Bendamustine Eugia is used in combination with medicines that affect the immune response, its effect on the bone marrow may be increased.
Cytotoxic medicines may reduce the effectiveness of live virus vaccines. Additionally, cytotoxic medicines increase the risk of infection after live virus vaccination (e.g., live virus vaccines).

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

Bendamustine Eugia may cause damage to genetic material and birth defects in animal studies. Bendamustine Eugia should not be used during pregnancy unless your doctor considers it absolutely necessary. If treatment is necessary, consult your doctor about possible harmful effects on the unborn child and consider genetic counseling.
Women of childbearing age who can become pregnant must use effective contraception before starting treatment with Bendamustine Eugia and during treatment. If you become pregnant during treatment with Bendamustine Eugia, you should immediately inform your doctor and consider genetic counseling.

Breastfeeding

Bendamustine Eugia should not be used during breastfeeding. If treatment with Bendamustine Eugia is necessary, you must stop breastfeeding.
Before taking any medicine, consult your doctor or pharmacist.

Fertility

Men should not father a child during treatment with Bendamustine Eugia or for 6 months after treatment. There is a risk that treatment with Bendamustine Eugia may cause infertility, so men should consult their doctor about sperm preservation before starting treatment.

Driving and using machines

Bendamustine Eugia has a significant impact on the ability to drive and use machines. You should not drive or operate machinery if you experience side effects such as dizziness or lack of coordination.

3. How to take Bendamustine Eugia

Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, check with your doctor or pharmacist. Bendamustine Eugia is given by infusion into a vein over 30-60 minutes, in different doses, either alone (monotherapy) or in combination with other medicines.
Treatment should not be started if your white blood cell count and/or platelet count falls below a certain level determined by your doctor.
Your doctor will check these parameters at regular intervals.

Chronic lymphocytic leukemia

Non-Hodgkin's lymphoma

Multiple myeloma

Treatment should be discontinued if your white blood cell count and/or platelet count falls below a certain level determined by your doctor. Treatment can be continued when your white blood cell and platelet counts increase.

Impaired liver or kidney function

Depending on the degree of liver impairment, it may be necessary to adjust the dose (by 30% in case of moderate liver impairment). No dose adjustment is necessary if you have kidney failure. Your doctor will decide whether a dose adjustment is necessary.

How the medicine is given

Treatment with Bendamustine Eugia should only be initiated by doctors experienced in the use of anticancer medicines. Your doctor will give you the appropriate dose of Bendamustine Eugia and take necessary precautions.
Your doctor will administer the infusion solution after preparing it according to the instructions.
The solution is administered intravenously as a short-term infusion over 30-60 minutes.

Duration of treatment

There is no generally applicable time limit for treatment with Bendamustine Eugia.
The duration of treatment depends on the disease and how you respond to treatment.
If you have any doubts or questions about treatment with Bendamustine Eugia, consult your doctor or nurse.

Missing a dose of Bendamustine Eugia

If you miss a dose of Bendamustine Eugia, your doctor will usually continue treatment according to the planned dosing schedule.

Stopping treatment with Bendamustine Eugia

Your doctor will decide whether to stop treatment or change the medicine.
If you have any further doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Some of the side effects listed below may be found in blood tests performed by your doctor.
The following definitions of frequency are used:

Tissue damage (necrosis) has been observed very rarely after accidental injection of Bendamustine Eugia outside the blood vessel (extravasation). A symptom of extravasation may be a burning sensation at the injection site. Consequences of extravasation can include pain and poorly healing skin damage.
The side effect that limits the dose of Bendamustine Eugia is bone marrow depression, which usually returns to normal after treatment. Bone marrow depression can lead to a decrease in blood cell counts, which can increase the risk of infections, anemia, or bleeding.

Very common:

• Low white blood cell count (reduced number of cells that fight infection in the blood)
• Reduced red blood cell count (reduced number of cells that carry oxygen in the blood)
• Low platelet count (reduced number of cells that help blood to clot)
• Infections
• Nausea (feeling sick)
• Vomiting
• Mouth inflammation
• Headache
• Increased creatinine levels in the blood (a waste product produced by muscles)
• Increased urea levels in the blood (a waste product produced in the body)
• Fever
• Fatigue (tiredness)

Common:

• Bleeding (hemorrhage)
• Metabolic disorders related to the release of cancer cell contents into the bloodstream
• Reduced red blood cell count, which can cause pale skin and weakness or shortness of breath (anemia)
• Low neutrophil count (a common type of white blood cell important for fighting infections)
• Hypersensitivity reactions, such as allergic skin inflammation (dermatitis), hives (urticaria)
• Increased liver enzyme activity (ASAT/ALAT, which may indicate liver inflammation or damage)
• Increased alkaline phosphatase activity (an enzyme produced mainly in the liver and bones)
• Increased bilirubin levels (a pigment produced during normal breakdown of red blood cells)
• Low potassium levels in the blood (a nutrient necessary for nerve and muscle function, including the heart)
• Heart problems (cardiac disorders)
• Heart rhythm disturbances (arrhythmias)
• Low or high blood pressure (hypotension or hypertension)
• Lung problems (respiratory disorders)

• Diarrhea
• Constipation
• Mouth pain (mouth inflammation)
• Loss of appetite
• Excessive hair loss
• Skin changes
• Absence of menstruation (amenorrhea)
• Pain
• Insomnia
• Chills
• Dehydration
• Dizziness
• Itchy rash (hives)

Uncommon:

• Fluid accumulation in the sac around the heart (pericardial effusion)
• Failure of the bone marrow to produce all types of blood cells (bone marrow failure)
• Acute leukemia
• Heart attack, chest pain (myocardial infarction)
• Heart failure

Rare:

• Blood infection (sepsis)
• Severe allergic reactions (anaphylactic reactions)
• Bone marrow depression, which can cause poor health or be detected in blood tests
• Reactions similar to anaphylaxis (anaphylactoid reactions)
• Drowsiness
• Voice loss (aphonia)
• Severe circulatory failure (cardiogenic shock)
• Redness of the skin (erythema)
• Skin inflammation
• Itching (pruritus)
• Rash (maculopapular rash)
• Excessive sweating (hyperhidrosis)

Very rare:

• Primary atypical pneumonia (pneumonia)
• Red blood cell destruction
• Sudden drop in blood pressure, sometimes with skin reactions or rash (anaphylactic shock)
• Taste disturbance
• Numbness or tingling (paresthesia)
• Poor general health and limb pain (peripheral neuropathy)
• Severe condition leading to blockage of a certain receptor in the nervous system
• Nervous system disorders
• Lack of coordination (ataxia)
• Brain inflammation
• Fast heart rate (tachycardia)
• Vein inflammation
• Scarring of lung tissue (pulmonary fibrosis)
• Bleeding from the esophagus (esophageal bleeding)
• Bleeding from the stomach or intestines
• Infertility
• Failure of multiple organs

Frequency not known:

• Liver failure
• Kidney failure
• Irregular or rapid heartbeat (atrial fibrillation)
• Painful red or purple spreading rash with blisters and/or other mucosal changes (e.g., in the mouth and on the lips), especially if you have previously experienced sensitivity to light, respiratory infection (e.g., bronchitis), and/or fever
• Drug rash in combination with rituximab
• Lung inflammation
• Bleeding from the lungs
• Excessive urination, including at night, and excessive thirst even after drinking fluids (nephrogenic diabetes insipidus)

There have been reports of cancer (myelodysplastic syndrome, acute myeloid leukemia) after treatment with Bendamustine Eugia. A clear link with Bendamustine Eugia could not be established.
You should immediately contact your doctor if you experience any of the following side effects (frequency not known):
Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. These can appear as red or circular patches on the skin, often with central blisters on the torso, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes, and may be preceded by fever and flu-like symptoms.
Widespread rash, high body temperature, swollen lymph nodes, and symptoms affecting various organs (drug reaction with eosinophilia and systemic symptoms, also known as DRESS syndrome or hypersensitivity syndrome).

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 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, you can help provide more information on the safety of this medicine.

5. How to store Bendamustine Eugia

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The expiry date refers to the last day of that month.
The vials may, but need not be, packaged in a protective plastic sleeve.
Attention to the shelf-life after opening or preparation of the solution.
Chemical and physical stability has been demonstrated for 3.5 hours at 25°C and up to 48 hours at 2°C - 8°C in polyethylene bags.
From a microbiological point of view, the product should be used immediately.
If not used immediately, the storage times and conditions before use are the responsibility of the user and are normally not more than 24 hours at 2°C to 8°C, unless reconstitution/dilution has been performed under controlled and validated aseptic conditions.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Bendamustine Eugia contains

The active substance is bendamustine hydrochloride.
One vial contains 25 mg of bendamustine hydrochloride (as monohydrate).
One vial contains 100 mg of bendamustine hydrochloride (as monohydrate).
After reconstitution, 1 ml of concentrate contains 2.5 mg of bendamustine hydrochloride (as monohydrate).
The other ingredient is mannitol.

What Bendamustine Eugia looks like and contents of the pack

Powder for concentrate for solution for infusion.
White to off-white lyophilized cake or powder.
Vials with a capacity of 20 ml with a neck diameter of 20 mm made of tubular orange glass type I, with gray bromobutyl rubber stoppers with a diameter of 20 mm and sealed with an aluminum seal with a polypropylene cap.
Vials with a capacity of 50 ml with a neck diameter of 20 mm made of tubular orange glass type I, with gray bromobutyl rubber stoppers with a diameter of 20 mm and sealed with an aluminum seal with a polypropylene cap.
Bendamustine Eugia is available in packs containing 1, 5, 10, or 20 vials of 25 mg bendamustine hydrochloride and 1, 5, or 10 vials of 100 mg bendamustine hydrochloride.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Eugia Pharma (Malta) Ltd.
Vault 14, level 2
Valletta Waterfront
Floriana, FRN1914
Malta
e-mail: [email protected]

Manufacturer/Importer:

APL Swift Services (Malta) Ltd.
HF26, Hal Far Industrial Estate, Hal Far
Birzebbugia, BBG 3000
Malta
Generis Farmacêutica, S.A.
Rua João de Deus 19, Venda Nova
2700-487 Amadora
Portugal
Arrow Génériques
26 Avenue Tony Garnier
69007 Lyon
France

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

Belgium:
Bendamustine Eugia 2.5 mg/ml powder for concentrate for solution for infusion / poudre pour solution à diluer pour perfusion / Pulver für ein Konzentrat zur Herstellung einer Infusionslösung
France:
BENDAMUSTINE ARROW 2.5 mg/ml, poudre pour solution à diluer pour perfusion
Germany:
Bendamustin PUREN 2.5 mg/ml Pulver für ein Konzentrat zur Herstellung einer Infusionslösung
Italy:
Bendamustina Aurobindo
Poland:
Bendamustine Eugia
Portugal: Bendamustina Generis
Spain: Bendamustina Aurovitas 2.5 mg/ml polvo para concentrado para solución para perfusión
EFG

Date of last revision of the leaflet: 03/2024

Information intended for healthcare professionals only:

As with all similar cytotoxic substances, due to the potential for genetic damage and cancer, nursing staff and doctors should take more stringent than usual precautions.
When handling Bendamustine Eugia, avoid inhalation (inhalation) of the medicine and its contact with the skin and mucous membranes (wear gloves, protective clothing, and possibly a face mask!). In case of contamination of any part of the body with the product, wash it thoroughly with soap and water and rinse the eyes with 0.9% (isotonic) saline solution. If possible, work on special, protected workstations (under laminar flow), with a single-use, fluid-impermeable absorbent sheet covering the work surface. Contaminated items are cytotoxic waste. Follow national guidelines for the disposal of materials with cytotoxic properties. Pregnant women should be excluded from working with cytotoxic products.
The infusion solution should be prepared by dissolving the contents of the Bendamustine Eugia vial in water for injection only, as follows:

• 1. Preparation of the concentrate
• A vial of Bendamustine Eugia containing 25 mg of bendamustine hydrochloride is first dissolved in 10 ml of water for injection by shaking.
• A vial of Bendamustine Eugia containing 100 mg of bendamustine hydrochloride is first dissolved in 40 ml of water for injection by shaking.
• 2. Preparation of the infusion solution After obtaining a clear solution (usually after 5-10 minutes), the recommended dose of Bendamustine Eugia should be immediately diluted in 0.9% (isotonic) saline solution to achieve a final volume of approximately 500 ml. Bendamustine Eugia should not be dissolved in other infusion or injection solutions. Bendamustine Eugia should not be mixed in an infusion with other substances.
• 3. Administration of the medicine The solution is administered by intravenous infusion over 30-60 minutes. The vials are for single use only. Any unused product or waste should be disposed of in accordance with local regulations.

In case of accidental injection of Bendamustine Eugia outside the blood vessel (extravasation), the infusion should be stopped immediately. The needle should be removed after a short aspiration. The affected tissue area should then be cooled. The arm should be elevated. Additional treatment, such as the use of corticosteroids, does not provide clear benefits (see section 4).