BENDAMUSTINE DR. REDDY'S 2.5 mg/ml POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Bendamustine Dr. Reddys 2.5 mg/ml powder for concentrate for solution for infusion EFG

Bendamustine hydrochloride

Read all of this leaflet carefully before you start using 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 or pharmacist.
• 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 experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Bendamustine Dr. Reddys and what is it used for
2. What you need to know before you use Bendamustine Dr. Reddys
3. How to use Bendamustine Dr. Reddys
4. Possible side effects
5. Storage of Bendamustine Dr. Reddys
6. Contents of the pack and other information

1. What is Bendamustine Dr. Reddys and what is it used for

Bendamustine is a medicine used to treat certain types of cancer (it is a cytotoxic medicine).

Bendamustine is used alone (monotherapy) or in combination with other medicines to treat the following types of cancer:

• Chronic lymphocytic leukemia, if combination chemotherapy with fludarabine is not suitable for you.
• Non-Hodgkin lymphomas, which have not responded, or have responded only for a short period, to previous treatment with rituximab.
• Multiple myeloma, if high-dose chemotherapy and autologous stem cell transplantation or treatments containing thalidomide or bortezomib are not suitable for you.

2. What you need to know before you use Bendamustine Dr. Reddys

Do not use Bendamustine Dr. Reddys:

• if you are allergic to bendamustine hydrochloride or any of the other ingredients of this medicine (listed in section 6)
• during breast-feeding, if treatment with Bendamustine Dr. Reddys is necessary during breast-feeding, you must stop breast-feeding (see section Warnings and precautions regarding breast-feeding).
• if you have severe liver dysfunction (damage to the functional cells of the liver)
• if you have yellowing of the skin or the whites of the eyes, caused by liver or blood problems (jaundice)
• if you have a severe disorder of bone marrow function (bone marrow depression) and severe alterations in the number of white blood cells and platelets in the blood
• if you have undergone major surgery in the 30 days prior to the start of treatment
• if you have had any infection, especially if it has been accompanied by a reduction in the number of white blood cells (leucopenia)
• in combination with yellow fever vaccines

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you start using Bendamustine Dr. Reddys

• if your bone marrow's ability to replace blood cells has been reduced. The number of white blood cells and platelets in your blood should be measured before you start treatment with Bendamustine Dr. Reddys, before each treatment cycle, and in the intervals between cycles.
• if you have infections. If you have signs of infection, such as fever or respiratory symptoms, you should contact your doctor.
• at any time during or after your treatment, inform your doctor immediately if you notice or someone notices in you: memory loss, difficulty thinking, difficulty walking, or loss of vision; these may be due to a rare but serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML).
• if you have skin reactions during treatment with bendamustine. Skin reactions can increase in severity.
• contact your doctor if you notice any suspicious changes in your skin because there may be an increased risk of certain types of skin cancer (non-melanoma skin cancer) with the use of this medicine.
• if you have a skin rash that is painful, red, or purple, and blisters and/or other lesions appear on the mucous membranes (e.g., mouth and lips), especially if you have previously had sensitivity to light, respiratory infections (e.g., bronchitis), and/or fever.
• if you have heart disease (e.g., heart attack, chest pain, severe heart rhythm disorders).

• if you notice pain on one side or if you see blood in your urine or if you urinate less. If your disease is very severe, your body may not be able to eliminate all the waste products of dying cancer cells. This is called tumor lysis syndrome and can cause kidney failure and heart problems within 48 hours of receiving the first dose of Bendamustine Dr. Reddys. Your doctor will make sure you are properly hydrated and will give you other medicines to prevent this from happening.
• if you have skin reactions during treatment with Bendamustine Dr. Reddys. Reactions can increase in intensity.
• if you have widespread painful red or purple rashes and blisters and/or other lesions that appear on the mucous membranes (e.g., mouth and lips), especially if you have previously had sensitivity to light, respiratory infections (e.g., bronchitis), and/or fever.
• if you have severe allergic or hypersensitivity reactions. You should pay attention to infusion reactions after your first treatment cycle.

At any time during or after your treatment, inform your doctor immediately if you notice or someone notices in you: memory loss, difficulty thinking, difficulty walking, or loss of vision; this may be due to a rare but serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML).

Talk to your doctor if you notice any suspicious changes in your skin because there may be an increased risk of certain types of skin cancer (non-melanoma skin cancer) with the use of this medicine.

Children and adolescents

There is no experience in children or adolescents with bendamustine hydrochloride.

Using Bendamustine Dr. Reddys with other medicines

Tell your doctor or pharmacistif you are using, have recently used, or might use any other medicines.

If Bendamustine Dr. Reddys is used in combination with medicines that inhibit blood cell production in the bone marrow, the effect on the bone marrow may be increased.

If Bendamustine Dr. Reddys is used in combination with medicines that alter your immune response, this effect may be increased.

Cytostatics may reduce the effectiveness of live virus vaccines. Additionally, cytostatics increase the risk of infection after vaccination with live virus vaccines (e.g., viral vaccination).

Pregnancy, breast-feeding, and fertility

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before using this medicine.

Pregnancy

Bendamustine Dr. Reddys may cause genetic damage and has caused malformations in animal studies. You should not use Bendamustine Dr. Reddys during pregnancy unless your doctor considers it clearly necessary. If you receive this treatment, you should ask your doctor to explain the risk of possible side effects of the treatment for your child, and genetic counseling is recommended.

If you are a woman of childbearing age, you must use effective contraceptive measures before and during treatment with bendamustine. If you become pregnant during treatment with bendamustine, you should inform your doctor immediately and seek genetic counseling.

If you are a man, you should not father a child during treatment with bendamustine and for up to 6 months after treatment. There is a risk that treatment with bendamustine may cause infertility; you may want to seek advice on sperm preservation before starting treatment.

Breast-feeding

Bendamustine Dr. Reddys should not be administered during breast-feeding. If you need treatment with Bendamustine Dr. Reddys during breast-feeding, you must stop breast-feeding. Talk to your doctor or pharmacist before taking this medicine.

Fertility

If you are a man, you should not father a child during treatment with Bendamustine Dr. Reddys and for up to 6 months after treatment. There is a risk that treatment with Bendamustine Dr. Reddys may cause infertility; you may want to seek advice on sperm preservation before starting treatment.

Driving and using machines

Bendamustine Dr. Reddys has a significant influence on the ability to drive and use machines. Do not drive or use machines if you experience side effects such as dizziness or lack of coordination.

3. How to use Bendamustine Dr. Reddys

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. Ask your doctor or pharmacist if you are not sure.

Bendamustine Dr. Reddys is administered into a vein over 30 to 60 minutes in various doses, either alone (monotherapy) or in combination with other medicines.

You cannot start treatment if your white blood cell (leukocyte) and/or platelet count is below certain levels.

Your doctor will measure these values periodically.

Chronic lymphocytic leukemia

Non-Hodgkin lymphomas

Multiple myeloma

Treatment must be stopped if the white blood cell (leukocyte) and/or platelet count is below certain levels. Treatment can be resumed when the leukocyte and platelet count has increased.

Kidney or liver impairment

The dose may need to be adjusted based on the degree of liver function impairment (by 30% in case of moderate liver impairment). No dose adjustment is necessary in case of kidney function impairment. Your doctor will decide if a dose adjustment is necessary.

How it is administered

Bendamustine Dr. Reddys can only be administered by doctors with experience in the treatment of tumors. Your doctor will administer the exact dose of Bendamustine Dr. Reddys and take the necessary precautions.

Your doctor will administer the infusion solution after proper preparation. The solution is administered into a vein as a short infusion over 30 to 60 minutes.

Duration of treatment

A specific duration of treatment with Bendamustine Dr. Reddys has not been defined. The duration of treatment depends on the disease and response to treatment.

If you have any concerns or questions about treatment with Bendamustine Dr. Reddys, talk to your doctor or nurse.

If you forget to use Bendamustine Dr. Reddys

If you miss a dose of Bendamustine Dr. Reddys, your doctor will usually continue with the normal dosing schedule.

If you stop treatment with Bendamustine Dr. Reddys

Your doctor will decide whether to stop treatment or use a different preparation.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people experience them. Some of the adverse effects listed below may appear after tests performed by your doctor.

The following frequencies are used to evaluate adverse reactions:

In very rare cases, tissue degeneration (necrosis) has been observed after Bendamustine leakage into the tissue surrounding blood vessels (extravascular). A burning sensation at the needle insertion site may be a sign of leakage outside the blood vessel. The consequences can be pain and skin healing problems.

The dose-limiting adverse effect of Bendamustina Dr. Reddys is an alteration of bone marrow function, which usually normalizes after treatment. Bone marrow function suppression can cause low blood cell counts, which can increase the risk of infection, anemia, or a higher risk of bleeding.

Very frequent:

Reduction of white blood cell count (the cells in your blood responsible for fighting disease) • Reduction of red blood pigment (hemoglobin: the protein responsible for transporting oxygen in the body) • Reduction of platelet count (colorless blood cells that collaborate in coagulation) • Infections • Nausea • Vomiting • Inflammation of the mucous membranes • Headache • Increase in blood creatinine concentration (a waste product produced by muscles) • Increase in blood urea concentration (a waste product) • Fever • Fatigue.

Frequent:

Bleeding (hemorrhage) • Alteration of metabolism caused by dying cancer cells releasing their contents into the bloodstream • Decrease in red blood cells, which can make the skin pale and cause weakness or difficulty breathing (anemia) • Reduction of neutrophil count (a common type of white blood cell important for fighting infections) • Hypersensitivity reactions, such as allergic skin inflammation (dermatitis), hives • Elevation of liver enzymes AST/ALT (which can indicate inflammation or damage to liver cells) • Increase in alkaline phosphatase enzyme (an enzyme synthesized mainly in the liver and bones) • Increase in bile pigment (a substance generated by the normal breakdown of red blood cells) • Decrease in blood potassium level (a nutrient necessary for the functioning of muscle and nerve cells, including those of the heart) • Cardiac dysfunction (palpitations, chest pain) • Alteration of heart rhythm (arrhythmia) • Elevation or decrease in blood pressure (hypotension or hypertension) • Alteration of lung function • Diarrhea • Constipation • Mouth ulcers (stomatitis) • Loss of appetite • Hair loss • Skin disorders • Absence of menstrual period (amenorrhea) • Pain • Insomnia • Chills • Dehydration • Dizziness • Itchy rash (urticaria).

Uncommon:

Fluid accumulation in the cardiac sac (fluid leakage into the pericardial space) • Ineffective production of blood cells in the bone marrow (the spongy material inside bones where blood cells are produced) • Acute leukemia • Heart attack, chest pain (myocardial infarction) • Heart failure

Rare:

Blood infection (sepsis) • Severe allergic hypersensitivity reactions (anaphylactic reactions) • Decrease in bone marrow function, which can make you feel unwell or appear in your blood tests • Signs similar to anaphylactic reactions (anaphylactoid reactions) • Drowsiness • Loss of voice (aphonia) • Acute circulatory collapse (insufficiency of blood circulation mainly of cardiac origin with inability to maintain oxygen and nutrient supply to tissues and elimination of toxins) • Redness of the skin (erythema) • Skin inflammation (dermatitis) • Itching (pruritus) • Skin rash (macular exanthema) • Excessive sweating (hyperhidrosis).

Very rare:

Primary atypical lung inflammation (pneumonia) • Breakdown of red blood cells • Rapid decrease in blood pressure sometimes with skin reactions or rash (anaphylactic shock) • Alteration of taste • Alteration of sensations (paresthesia) • Discomfort and pain in the limbs (peripheral neuropathy) • Severe condition that causes blockage of a specific receptor in the nervous system • Nervous system disorders • Lack of coordination (ataxia) • Brain inflammation (encephalitis) • Increase in heart rate (tachycardia) • Inflammation of the veins (phlebitis) • Tissue formation in the lungs (pulmonary fibrosis) • Hemorrhagic inflammation of the esophagus (esophagitis) • Stomach or intestinal bleeding • Infertility • Multi-organ failure

Unknown:

Liver failure • Kidney failure • Irregular and often rapid heart rate (atrial fibrillation) • Red or purple painful rash that spreads and begins to appear with blisters and/or other lesions on mucous membranes (e.g., mouth and lips), especially if you have had previous sensitivity to light, respiratory infections (e.g., bronchitis), and/or fever • Drug rash in combination therapy with rituximab • Pneumonitis • Lung bleeding • Excessive urination, even at night, and excessive thirst even after drinking liquids (nephrogenic diabetes insipidus)

There have been reports of tumors (myelodysplastic syndromes, acute myeloid leukemia (AML), bronchial carcinoma) after treatment with Bendamustina Dr. Reddys. A clear relationship with Bendamustina Dr. Reddys could not be determined.

Consult your doctor or seek medical attention immediatelyif you notice any of the following side effects (unknown frequency):

• Severe skin rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis. These can appear as white-red spots or circular patches often with central blisters on the trunk, skin peeling, mouth ulcers, throat, nose, genitals, and eyes, and may be preceded by fever and flu-like symptoms.
• Generalized rash, high body temperature, enlarged lymph nodes, and other organs involved (drug reaction with eosinophilia and systemic symptoms, also known as DRESS or drug hypersensitivity syndrome)

If any of the side effects worsen or if you notice any side effect not mentioned in this prospectus, inform your doctor.

Adverse effect reporting

If you experience any type of adverse effect, consult your doctor, hospital pharmacist, or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Medicines and Healthcare Products Agency's pharmacovigilance system: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Bendamustina Dr. Reddys

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date shown on the label and packaging after "EXP". The first two digits correspond to the month and the last four digits indicate the year. The expiration date is the last day of the month indicated.

Store in the outer packaging to protect it from light.

Check the validity period before opening or preparing the solution.

Bendamustina Dr. Reddys does not contain preservatives.

After reconstitution and dilution, chemical and physical stability has been demonstrated for 3.5 hours at 25°C / 60% RH and 2 days at 2°C to 8°C in polyethylene bags.

From a microbiological point of view, the product must be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and should not normally exceed 24 hours between 2°C and 8°C, unless reconstitution/dilution (etc.) has taken place in a controlled and validated aseptic environment.

Medicines should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Bendamustina Dr. Reddys

• The active ingredient is bendamustine hydrochloride.

1 vial contains 25 mg of bendamustine hydrochloride.

1 vial contains 100 mg of bendamustine hydrochloride.

When reconstituted, 1 ml of concentrate contains 2.5 mg of bendamustine hydrochloride

• The other component is mannitol (E421)

Appearance of the Product and Package Contents

White to off-white lyophilized powder in a brown glass vial with a rubber stopper and an aluminum flip-top cap.

The 25 ml vials contain 25 mg of bendamustine hydrochloride and are available in packs of 1, 5, 10, and 20 vials.

The 50 ml vials contain 100 mg of bendamustine hydrochloride and are available in packs of 1 and 5 vials.

Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Reddy Pharma Iberia, S.A.

Avda Josep Tarradellas, nº 38

08029 Barcelona

Spain

Phone: 93 355 49 16

Fax: 93 355 49 61

Manufacturer:

DR. REDDYS LABORATORIES (UK) LTD.

6, Riverview Road

HU17 0LD Beverley, East Yorkshire

United Kingdom

or

BETAPHARM ARZNEIMITTEL GMBH

Kobelweg 95

86156 Augsburg

Germany

or

Synthon Hispania S.L.

Polígono Las Salinas, Carrer de Castelló 1

08830 Sant Boi de Llobregat, Barcelona

Spain

Phone: 936 40 15 16

or

Synthon S.R.O.

Brnenska 32/cp. 597

678 01 Blansko

Czech Republic

Phone: +420516427311

Fax: +420516417350

This medicine has been authorized in the European Economic Area under the following names:

France Bendamustine Dr. Reddy's 2.5 mg/ml, powder for concentrate for solution for infusion

Germany Bendamustin HCl beta 2.5 mg/ml powder for concentrate for solution for infusion

Italy Bendamustina Dr. Reddy's

Spain Bendamustina Dr. Reddys 2.5 mg/ml powder for concentrate for solution for infusion EFG

United Kingdom Bendamustine hydrochloride 2.5 mg/ml powder for concentrate for solution for infusion

Date of the last revision of this prospectus:March 2025

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Healthcare Products (AEMPS) http://www.aemps.gob.es

This information is intended only for doctors or healthcare professionals:

As with all similar cytotoxics, nursing staff and doctors must take extreme safety precautions due to the potential genotoxic and carcinogenic effects of the preparation.

Avoid inhalation (inhalation) and contact with skin and mucous membranes when handling bendamustine (wear gloves, protective clothing, and, if possible, a mask!). If any part of the body is contaminated, clean it carefully with water and soap, and rinse the eyes with 0.9% isotonic saline solution. If possible, it is recommended to work on a special safety bench (laminar flow) with a disposable, liquid-impermeable absorbent sheet. Contaminated items are cytostatic waste. Please follow national guidelines for the disposal of cytostatic material! Pregnant women on the staff should not work with cytostatics.

The ready-to-use solution must be prepared by dissolving the contents of a bendamustine vial exclusively in water for injections, as indicated below:

1. Preparation of the concentrate
   • First, dissolve a bendamustine vial containing 25 mg of bendamustine hydrochloride in 10 ml, shaking it.
   • First, dissolve a bendamustine vial containing 100 mg of bendamustine hydrochloride in 40 ml, shaking it.

1. Preparation of the infusion solution

As soon as a clear solution is obtained (after 5 to 10 minutes, usually), immediately dissolve the total recommended dose of bendamustine in 0.9% isotonic saline solution to achieve a final volume of approximately 500 ml. Bendamustine should not be dissolved with other infusion or injection solutions. Bendamustine should not be mixed in infusion with other substances.

1. Administration

The solution is administered by intravenous infusion over 30-60 minutes.

The vials are for single use.

Any unused product or waste material must be disposed of in accordance with local requirements.

Inadvertent injection outside the blood vessels (extravascular injection) should be stopped immediately. The needle should be removed after a short aspiration. From then on, the affected tissue area should be cooled. The arm should be elevated. Additional treatments such as the use of corticosteroids are of unclear benefit (see section 4).