Package Leaflet: Information for the User

Bendamustine Dr. Reddys 2.5 mg/ml Powder for Concentrate for Solution for Infusion EFG

Bendamustine Hydrochloride

Read this leaflet carefully before you start taking 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 or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

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

2. What you need to know before you start taking 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 additional information

Bendamustina is a medication used for the treatment of certain types of cancer (it is a cytotoxic medication).

Bendamustina is used alone (monotherapy) or in combination with other medications for the treatment of the following types of cancer:

• Chronic lymphocytic leukemia, if combination chemotherapy with fludarabine is not suitable for you.
• Non-Hodgkin lymphomas that have not responded, or have only responded for a short period of time, after previous treatment with rituximab.
• Multiple myeloma, if high doses of chemotherapy and an autotransplant of progenitor cells or treatments containing thalidomide or bortezomib are not suitable for you.

No use Bendamustina Dr. Reddys:

• if you are allergic to hydrochloride of bendamustine or to any of the other components of this medication (listed in section 6)
• during breastfeeding,if the treatment with Bendamustina Dr. Reddys is necessary during breastfeeding, you must interrupt breastfeeding (see section Advertencias and precauciones sobre la lactancia).
• if you have a severe liver dysfunction (liver cell damage)
• if you have a yellowish discoloration of the skin or the white of the eyes, caused by liver or blood problems (jaundice)
• if you have a severe bone marrow function disorder (bone marrow depression) and severe alterations of the number of white blood cells and platelets in the blood
• if you have undergone a major surgical intervention in the 30 days prior to the start of treatment
• if you have had any infection, especially if accompanied by a reduction in the number of white blood cells (leucocitopenia)
• in combination with yellow fever vaccines

Advertencias and precauciones

Consult your doctor, pharmacist or nurse before starting to use Bendamustina Dr. Reddys

• if youhave reduced the ability of your bone marrow to replace blood cells.You must measure the number of white blood cells and platelets in the blood before starting treatment with Bendamustina Dr. Reddys, before each cycle of treatment and in the intervals between cycles.
• in case ofinfections. If you present signs of infection, such as fever or respiratory symptoms, you must contact your doctor.
• at any time during or after your treatment, immediately inform your doctor 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 severe brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML).
• in case of skin reactions during treatment with bendamustina. Skin reactions can increase in severity.
• contact your doctor if you notice any suspicious changes in the skin because there may be a higher risk of certain types of skin cancer (non-melanoma skin cancer) with the use of this medication.
• in case of painful, red or purple rash that spreads and starts to appear blisters and/or other lesions on the mucous membrane (for example, mouth and lips), particularly if you had previously had sensitivity to light, respiratory system infections (for example, bronchitis) and/or fever.
• if you have aheart disease(for example, heart attack, chest pain, severe heart rhythm disorders).

• if you noticeside pain or if you observe blood in the urine or if you urinate less. If your disease is very severe, it is possible that your body cannot eliminate all the waste products of the dying cancer cells. This is called tumor lysis syndrome and can cause kidney failure and heart problems in the 48 hours following the administration of the first dose of Bendamustina Dr. Reddys. Your doctor will ensure that you are adequately hydrated and will give you other medications to prevent this from happening.
• if you presentskin reactionsduring treatment with Bendamustina Dr. Reddys. Reactions can increase in intensity.
• in caseof painful, widespread rashes of red or purple color and blisters and/or other lesions that start to appear on the mucous membrane (for example, mouth and lips), particularly if you had previously had sensitivity to light, respiratory system infections (for example, bronchitis) and/or fever.
• in case ofsevere allergic or hypersensitivity reactions. You must pay attention to reactions to infusion after your first cycle of treatment.

At any time during or after your treatment, immediately inform your doctor 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 severe brain infection that can be fatal. (progressive multifocal leukoencephalopathy or PML).

Inform your doctor if you notice any suspicious changes in the skin because there may be a higher risk of certain types of skin cancer (non-melanoma skin cancer) with the use of this medication.

Children and adolescents

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

Use of Bendamustina Dr. Reddys with other medications

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

If Bendamustina Dr. Reddys is used in combination with medications that inhibit the formation of blood cells in the bone marrow, the effect on the bone marrow can be intensified.

If Bendamustina Dr. Reddys is used in combination with medications that alter your immune response, this effect can be intensified.

Cytostatics can reduce the effectiveness of live virus vaccines. In addition, cytostatics increase the risk of infection after vaccination with live virus vaccines (for example, viral vaccination).

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or intend to become pregnant, consult your doctor before using this medication

Pregnancy

Bendamustina Dr. Reddys may cause genetic damage and has caused malformations in studies conducted with animals. You must not use Bendamustina Dr. Reddys during pregnancy unless your doctor considers it clearly necessary. If you receive this treatment, you must ask a doctor to explain the risk of possible adverse 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 must immediately inform your doctor and seek genetic counseling.

If you are a man, you must not father children during treatment with bendamustine and for 6 months after the same. There is a risk that treatment with bendamustine may cause sterility; you may want to seek advice on sperm conservation before starting treatment.

Breastfeeding

Bendamustina Dr. Reddys must not be administered during breastfeeding. If you need treatment with Bendamustina Dr. Reddys during breastfeeding, you must suspend it. Consult your doctor or pharmacist before taking this medication.

Fertility

If you are a man, you must not father children during treatment with Bendamustina Dr. Reddys and for 6 months after the same. There is a risk that treatment with Bendamustina Dr. Reddys may cause sterility; you may want to seek advice on sperm conservation before starting treatment.

Driving and using machines

Bendamustina Dr. Reddys has a significant influence on your ability to drive and use machines.Do not drive or use machines if you experience adverse effects, such as dizziness or lack of coordination.

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. Consult with your doctor or pharmacist if you are unsure.

Bendamustina Dr. Reddys is administered via a vein for 30 to 60 minutes in various doses, either alone (monotherapy) or combined with other medications.

You will not be able to start treatment if your white blood cell count (leukocytes)and/or platelet count is below certain levels.

Your doctor will measure these values periodically.

Chronic Lymphocytic Leukemia

Non-Hodgkin Lymphomas

Multiple Myeloma

Treatment should be discontinued if the white blood cell count (leukocytes) and/or platelet count is below certain levels.Treatment may be resumed when the leukocyte and platelet count has increased.

Renal or Hepatic Insufficiency

Dose adjustment may be necessary based on the degree of liver function deterioration (30% in case of moderate liver deterioration). No dose adjustment is necessary in case of renal function alteration. Your doctor will decide if a dose adjustment is necessary.

How to Administer

Bendamustina Dr. Reddys can only be administered by experienced oncologists. Your doctor will administer the exact dose of Bendamustina Dr. Reddys and take necessary precautions.

Your doctor will administer the prepared solution via a vein as a brief infusion for 30 to 60 minutes.

Treatment Duration

The exact duration of treatment with Bendamustina Dr. Reddys has not been defined. Treatment duration depends on the disease and response to treatment.

If you have any concerns or doubts about treatment with Bendamustina Dr. Reddys, speak with your doctor or nurse.

If you forgot to use Bendamustina Dr. Reddys

If you forget a dose of Bendamustina Dr. Reddys, your doctor will usually proceed with the normal dosing schedule.

If you interrupt treatment with Bendamustina Dr. Reddys

Your doctor will decide if treatment should be discontinued or if a different preparation should be used.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.Some of the side 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 Bendamustina leakage into the tissue surrounding blood vessels (extravascular). A burning sensation at the site of needle insertion may be a sign of leakage outside the blood vessel. The consequences may be pain and skin healing problems.

The dose-limiting side effect of Bendamustina Dr. Reddys is a change in bone marrow function, which usually normalizes after treatment. Bone marrow function suppressionmay cause low blood cell levels, which in turn may increase the risk of infection, anemia, or a higher risk of bleeding.

Very common:

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

Common:

Bleeding (hemorrhage) • Metabolic alteration caused by dying cancer cells, which release their contents into the circulatory system • Decreased red blood cells, which may cause pale skin and cause weakness or difficulty breathing (anemia) • Decreased neutrophil count (a common type of white blood cell important for fighting infections) • Hypersensitivity reactions, such as allergic inflammation of the skin (dermatitis), urticaria • Elevated liver enzymes AST/ALT(which may indicate inflammation or damage to liver cells)• Increased alkaline phosphatase enzyme(an enzyme synthesized mainly in the liver and bones)• Increased bile pigment(a substance generated by the normal degradation of red blood cells)• Decreased blood potassium levels(a nutrient necessary for the functioning of muscle and nerve cells, including those of your heart)• Cardiac function alteration (palpitations, angina pectoris) • Cardiac rhythm alteration (arrhythmia) • Elevated or decreased blood pressure (hypotension or hypertension) • Pulmonary function alteration • Diarrhea • Constipation • Mouth ulcers (stomatitis) • Loss of appetite • Hair loss • Skin changes • Amenorrhea (absence of menstruation) • Pain • Insomnia • Chills • Dehydration • Dizziness• Eruption with itching (urticaria).

Uncommon:s:

Accumulation of fluid in the heart sac (pericardial effusion) • Ineffective production of blood cells in the bone marrow (the spongy material inside bones where blood cells are produced) • Acute leukemia • Myocardial infarction, chest pain (myocardial infarction) • Heart failure

Rare:

Blood infection (sepsis) • Severe allergic hypersensitivity reactions (anaphylactic reactions) • Decreased bone marrow function, which may 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 (circulatory insufficiency mainly of cardiac origin with inability to maintain oxygen and nutrient supply to tissues and elimination of toxins) • Skin redness (erythema) • Skin inflammation (dermatitis) • Itching (pruritus) • Skin rash (macular exanthema) • Excessive sweating (hyperhidrosis).

Very rare:

Atypical primary inflammation of the lungs (pneumonia) • Red blood cell lysis • Rapid decrease in blood pressure sometimes with skin reactions or rash (anaphylactic shock) • Alteration of taste • Alteration of sensations (paresthesia) • Unpleasant and painful sensations in the extremities (peripheral neuropathy) • Severe condition causing blockage of a specific receptor in the nervous system • Nervous system disorders • Lack of coordination (ataxia) • Inflammation of the brain (encephalitis) • Increased heart rate (tachycardia) • Inflammation of the veins (phlebitis) • Formation of tissue in the lungs (pulmonary fibrosis) • Hemorrhagic inflammation of the esophagus (hemorrhagic esophagitis) • Bleeding of the stomach or intestine • Infertility • Multi-organ insufficiency

Unknown:

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

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.

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

• Severe skin eruptions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. These may appear as white or reddish macules 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 urticaria, high body temperature, swollen lymph nodes, and other organs involved (drug reaction with eosinophilia and systemic symptoms, also known as DRESS or drug hypersensitivity syndrome)

If any side effects worsen or if you notice any side effects not mentioned in this leaflet, inform your doctor.

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor, hospital pharmacist or nurse, even if it is a possible adverse reaction that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicinal Products for Human Use: https://www.notificaram.es. By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the label and on the packaging after “CAD”. 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 standpoint, the product should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and should normally not exceed 24 hours between 2 ° and 8 ° C, unless reconstitution / dilution (etc.) has taken place under controlled conditions and in validated aseptic conditions.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications you do not need. This will help protect the environment.

Composition of Bendamustine 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 contents of the package

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

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

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

Only some pack sizes may be marketed.

Holder of the marketing authorization and responsible manufacturer

Holder of the marketing authorization:

Reddy Pharma Iberia, S.A.

Avda Josep Tarradellas, nº 38

08029 Barcelona

Spain

Telephone: 93 355 49 16

Fax: 93 355 49 61

Responsible 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

Telephone: 936 40 15 16

or

Synthon S.R.O.

Brnenska 32/cp. 597

678 01 Blansko

Czech Republic

Telephone: +420516427311

Fax: +420516417350

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

FranceBendamustine Dr. Reddy´s 2.5 mg/ml, powder for solution for infusion

GermanyBendamustin HCl beta 2.5 mg/ml Powder for a concentrate to prepare an infusion solution

ItalyBendamustina Dr. Reddy's

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

United KingdomBendamustine hydrochloride 2.5 mg/ml Powder for concentrate for solution for infusion

Last review date of this leaflet:March 2025

Detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es

This information is intended solely for medical professionals or healthcare professionals:

As with all similar cytotoxics, nursing staff and doctors must exercise extreme caution due to the potential genotoxicity and carcinogenicity of the preparation.

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

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

1. Preparation of the concentrate

• First, dissolve a vial of bendamustine containing 25 mg of bendamustine hydrochloride in 10 ml, agitating it.
• First, dissolve a vial of bendamustine containing 100 mg of bendamustine hydrochloride in 40 ml, agitating it.

2. Preparation of the infusion solution

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

3. Administration

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

The vials are for single use only.

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

Unintentional injection outside the blood vessels (extravascular injection) must 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 not clearly beneficial (see section 4).