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

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

Bendamustina 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, talk to your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of this leaflet

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

1. What Bendamustina Dr. Reddys is and what it is 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 that have not responded, or have responded only for a short period of time, to previous treatment with rituximab.
• multiple myeloma, if high-dose chemotherapy with autologous progenitor cell transplantation or treatments containing thalidomide or bortezomib are not suitable for you.

2. What you need to know before starting Bendamustina Dr. Reddys

Do not use Bendamustina Dr. Reddys:

• 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 Bendamustina Dr. Reddys is necessary during breastfeeding, you must discontinue breastfeeding (see section Warnings and precautions on breastfeeding)
• if you have severe hepatic dysfunction (damage to the liver's functional cells)
• if you have yellowing of the skin or whites of the eyes caused by liver or blood problems (jaundice)
• if you have severe bone marrow function disorder (bone marrow suppression) and severe abnormalities in white blood cell and platelet counts
• if you have undergone major surgery within the previous 30 days before starting treatment
• if you have had any infection, especially if accompanied by a reduction in white blood cells (leucopenia)
• in combination with yellow fever vaccines

Warnings and precautions

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

• if your bone marrow’s ability to replace blood cells has been reduced. The number of white blood cells and platelets in the blood should be measured before starting treatment with Bendamustina Dr. Reddys, before each treatment cycle, and between cycles.

• if you have infections. If you experience signs of infection such as fever or pulmonary symptoms, contact your doctor.

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

• if you experience skin reactions during treatment with bendamustine. Skin reactions may increase in severity.

• contact your doctor if you notice any suspicious changes in the skin, as there may be an increased risk of certain types of non-melanoma skin cancer with the use of this medicine.

• if you develop a painful red or purple rash that spreads and blisters and/or other lesions begin to appear on mucous membranes (e.g., mouth and lips), particularly if you previously had light sensitivity, respiratory tract infections (e.g., bronchitis), and/or fever.

• if you have a heart disease (e.g., heart attack, chest pain, serious heart rhythm disorders).

• if you experience pain in one side of your body or notice blood in your urine or reduced urine output. If your condition is very severe, your body may be unable to eliminate waste products from dying cancer cells. This is known as tumor lysis syndrome and may lead to kidney failure and heart problems within 48 hours after the first dose of Bendamustina Dr. Reddys. Your doctor will ensure you are adequately hydrated and will give you other medications to prevent this.

• if you experience skin reactions during treatment with Bendamustina Dr. Reddys. Reactions may increase in intensity.

• if you develop widespread, painful red or purple rashes with blisters and/or other lesions appearing on mucous membranes (e.g., mouth and lips), particularly if you previously had light sensitivity, respiratory tract infections (e.g., bronchitis), and/or fever.

• if you experience severe allergic or hypersensitivity reactions. Pay attention to infusion-related reactions after your first treatment cycle.

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

Contact your doctor if you notice any suspicious changes in your skin, as there may be an increased risk of certain types of non-melanoma skin cancer with the use of this medicine.

Children and adolescents

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

Use of Bendamustina Dr. Reddys with other medicines

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

If Bendamustina Dr. Reddys is used in combination with medicines that suppress bone marrow blood cell formation, the effect on the bone marrow may be intensified.

If Bendamustina Dr. Reddys is used in combination with medicines that affect your immune response, this effect may be intensified.

Cytostatic agents may reduce the effectiveness of live virus vaccines. In addition, cytostatic agents increase the risk of infection following vaccination with live virus vaccines (e.g., viral vaccination).

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Pregnancy

Bendamustina Dr. Reddys may cause genetic damage and has caused malformations in animal studies. You must not use Bendamustina Dr. Reddys during pregnancy unless clearly necessary as determined by your doctor. If you receive this treatment, you should ask your doctor to explain the risk of possible adverse effects of the treatment on your unborn child, and genetic counseling is recommended.

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

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

Breastfeeding

Bendamustina Dr. Reddys must not be administered during breastfeeding. If treatment with Bendamustina Dr. Reddys is required during breastfeeding, you must discontinue breastfeeding. Consult your doctor or pharmacist before taking this medicine.

Fertility

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

Driving and use of machines

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

3. How to use Bendamustina Dr. Reddys

Follow exactly the instructions for administration of this medicine given by your doctor or pharmacist. Consult your doctor or pharmacist if you are unsure.

Bendamustina Dr. Reddys is administered intravenously over 30 to 60 minutes at various doses, either alone (monotherapy) or in combination with other medicines.

You cannot start treatment if your white blood cell (leucocyte) count 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 (leukocyte) and/or platelet count falls below certain levels. Treatment may be resumed when the leukocyte and platelet counts have increased.

Renal or hepatic impairment

Dosage adjustment may be necessary depending on the degree of liver function impairment (by 30% in case of moderate liver impairment). Dosage adjustment is not required in case of kidney function impairment. Your doctor will decide whether dosage adjustment is necessary.

How it is administered

Bendamustina Dr. Reddys must only be administered by physicians experienced in the treatment of tumors. Your doctor will administer the exact dose of Bendamustina Dr. Reddys and take the necessary precautions.

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

Duration of treatment

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

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

If you forget to use Bendamustina Dr. Reddys

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

If you interrupt treatment with Bendamustina Dr. Reddys

Your doctor will decide whether treatment should be interrupted or whether another preparation should be used.

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 may produce adverse effects, although not everyone experiences them. Some of the adverse effects listed below may occur following tests performed by your doctor.

The following frequencies are used to assess adverse reactions:

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

The dose-limiting adverse effect of Bendamustina Dr. Reddys is bone marrow dysfunction, which usually resolves after treatment. Suppression of bone marrow function may lead to low blood cell counts, thereby increasing the risk of infection, anemia, or a higher risk of bleeding.

Very common:

Reduction in white blood cell count (blood cells responsible for fighting disease) • Reduction in red blood pigment (hemoglobin: the protein responsible for oxygen transport in the body) • Reduction in platelet count (colorless blood cells involved in clotting) • Infections • Nausea • Vomiting • Mucosal 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 disturbance caused by dying cancer cells releasing their contents into the bloodstream • Reduction in red blood cells, which may cause pale skin, weakness, or difficulty breathing (anemia) • Reduction in neutrophil count (a common type of white blood cell important for fighting infections) • Hypersensitivity reactions, such as allergic skin inflammation (dermatitis), urticaria • Elevation of liver enzymes AST/ALT (which may indicate inflammation or damage to liver cells) • Increase in alkaline phosphatase enzyme (an enzyme mainly produced in the liver and bones) • Increase in bile pigment (a substance generated by normal breakdown of red blood cells) • Decreased blood potassium levels (a nutrient necessary for muscle and nerve cell function, including in the heart) • Cardiac dysfunction (palpitations, angina pectoris) • Cardiac rhythm disturbances (arrhythmia) • Increase or decrease in blood pressure (hypotension or hypertension) • Pulmonary function impairment • Diarrhea • Constipation • Mouth ulcers (stomatitis) • Loss of appetite • Hair loss • Skin disorders • Absence of menstrual periods (amenorrhea) • Pain • Insomnia • Chills • Dehydration • Dizziness • Itchy rash (urticaria).

Uncommon:

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

Rare:

Blood infection (sepsis) • Severe hypersensitivity allergic reactions (anaphylactic reactions) • Decreased bone marrow function, which may make you feel unwell or appear in blood tests • Symptoms resembling anaphylactic reactions (anaphylactoid reactions) • Somnolence • Loss of voice (aphonia) • Acute circulatory collapse (failure of blood circulation, primarily of cardiac origin, with inability to maintain oxygen and nutrient supply to tissues and toxin elimination) • Skin redness (erythema) • Skin inflammation (dermatitis) • Itching (pruritus) • Skin rash (macular exanthema) • Excessive sweating (hyperhidrosis).

Very rare:

Atypical primary inflammation of the lungs (pneumonia) • Breakdown of red blood cells • Rapid decrease in blood pressure sometimes accompanied by skin reactions or rash (anaphylactic shock) • Altered sense of taste • Altered sensations (paresthesia) • Discomfort and pain in the extremities (peripheral neuropathy) • Serious condition causing blockade of a specific receptor in the nervous system • Disorders of the nervous system • Lack of coordination (ataxia) • Brain inflammation (encephalitis) • Increased heart rate (tachycardia) • Vein inflammation (phlebitis) • Tissue formation in the lungs (pulmonary fibrosis) • Hemorrhagic esophageal inflammation (hemorrhagic esophagitis) • Bleeding from stomach or intestine • Infertility • Multi-organ failure

Not known:

Liver failure • Kidney failure • Irregular and often rapid heart rate (atrial fibrillation) • Painful red or purplish rash that spreads and begins to blister and/or other lesions appear on mucous membranes (e.g., mouth and lips), particularly if you previously had photosensitivity, respiratory infections (e.g., bronchitis), and/or fever • Drug rash during combination therapy with rituximab • Pneumonitis • Bleeding from the lungs • Excessive urination, even at night, and excessive thirst even after drinking fluids (nephrogenic diabetes insipidus)

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

Contact your doctor or seek immediate medical attention if you notice any of the following side effects (frequency not known):

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

If any of the side effects worsen or if you notice any side effects not listed 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 not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. Storage of Bendamustine Dr. Reddy's

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

Do not use this medicine after the expiry date stated on the label and packaging following "EXP". The first two digits indicate the month and the last four digits the year. The expiry date refers to the last day of the specified month.

Store in the outer packaging to protect from light.

Check the shelf life before opening or preparing the solution.

Bendamustine Dr. Reddy's 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 for 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 prior to use are the responsibility of the user and should normally not exceed 24 hours between 2 °C and 8 °C, unless reconstitution/dilution (etc.) has taken place 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 and packaging that you no longer need. This will help protect the environment.

6. Contents of the container and other information

Composition of Bendamustine Dr. Reddys

• The active substance is bendamustine hydrochloride.

One vial contains 25 mg of bendamustine hydrochloride.
One vial contains 100 mg of bendamustine hydrochloride.

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

• The other ingredient is mannitol (E421).

Appearance of the product and contents of the pack

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

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

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

Only some 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
Telephone: 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
Tel: 936 40 15 16

or

Synthon S.R.O.
Brnenska 32/cp. 597
678 01 Blansko
Czech Republic
Tel: +420516427311
Fax: +420516417350

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

France: Bendamustine Dr. Reddy´s 2.5 mg/ml, poudre pour solution à diluer pour perfusion
Germany: Bendamustin HCl beta 2.5 mg/ml Pulver für ein Konzentrat zur Herstellung einer Infusionslösung
Italy: Bendamustina Dr. Reddy's
Spain: Bendamustina Dr. Reddys 2.5 mg/ml polvo para concentrado para solución para perfusión EFG
United Kingdom: Bendamustine hydrochloride 2.5 mg/ml Powder for concentrate for solution for infusion

Date of the most recent review of this summary: March 2025

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es

This information is intended for healthcare professionals only:

As with all similar cytotoxic agents, nursing staff and physicians must take extreme care due to the potential genotoxic and carcinogenic properties of this preparation.

Avoid inhalation (inspiration) 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 becomes contaminated, wash carefully with water and soap, and rinse eyes with 0.9% isotonic saline solution. If possible, work should be performed on a special safety workstation (laminar flow hood) using a liquid-proof disposable absorbent pad. Contaminated materials are cytostatic waste. Please follow national regulations for the disposal of cytostatic material. Pregnant healthcare personnel should not handle cytostatic agents.

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

1. Preparation of the concentrate

   • First, dissolve one vial containing 25 mg of bendamustine hydrochloride in 10 ml, with agitation.
   • First, dissolve one vial containing 100 mg of bendamustine hydrochloride in 40 ml, with agitation.

2. Preparation of the infusion solution

Immediately after obtaining a clear solution (usually within 5 to 10 minutes), immediately dilute the recommended total dose of bendamustine in 0.9% isotonic saline solution to achieve a final volume of approximately 500 ml. Bendamustine must not be dissolved in other infusion or injection solutions. Bendamustine must not be mixed in the same infusion with other substances.

3. Administration

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

The vials are for single use only.

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

Extravasation (inadvertent leakage outside blood vessels) must be stopped immediately. The needle should be withdrawn after a brief aspiration. Thereafter, the affected tissue area should be cooled. The arm should be elevated. Additional treatments such as the use of corticosteroids have not been clearly shown to be beneficial (see section 4).