Prospecto: information for the user

Bendamustine Glenmark 2.5 mg/ml powder for concentrate for solution for infusion EFG

Bendamustine hydrochloride

Read this prospect carefully before starting to use the medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only to you and should not be given to other people, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if they are not listed in this prospect.See section 4.

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

2. What you need to know before starting to use Bendamustine Glenmark

3. How to use Bendamustine Glenmark

4. Possible adverse effects

5. Storage of Bendamustine Glenmark

6. Contents of the pack and additional information

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

Bendamustina Glenmark 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 treatments containing talidomida or bortezomib are not suitable for you.

No use BendamustinaGlenmark

• If you are allergic to hydrochloride bendamustine or any of the other components of this medication (listed in section 6).
• During breastfeeding, if Bendamustina Glenmark treatment is necessary during breastfeeding, you must interrupt breastfeeding (see Advertencias y precauciones section)
• If you have severe liver dysfunction (liver cell functional damage)
• If you present yellowish skin discoloration or white eye discoloration, caused by liver or blood problems (jaundice)
• If you present severe bone marrow dysfunction 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 accompanied by a reduction in the number of white blood cells (leucocitopenia)
• In combination with yellow fever vaccines

Advertencias y precauciones

Consult your doctor before starting to use Bendamustina Glenmark

• In case your bone marrow has reduced its ability to replace blood cells. You must measure the number of white blood cells and platelets in the blood before starting treatment with Bendamustina Glenmark, before each treatment cycle, and between cycles.
• In case of infections. If you present signs of infection, such as fever or respiratory symptoms, you must contact your doctor.
• If you present skin reactions during treatment with Bendamustina Glenmark. Reactions can increase in intensity.
• In case of widespread painful red or purple rashes and blisters and/or other lesions that appear on the mucous membrane (e.g. mouth and lips), particularly if you have had previous sensitivity to light, respiratory infections (e.g. bronchitis), and/or fever.
• If you have a heart disease (e.g., heart attack, chest pain, severe heart rhythm disorders).
• If you experience pain in the side 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 dying cancer cells. This is called tumor lysis syndrome and can cause kidney failure and heart problems within 48 hours after the first dose of Bendamustina Glenmark. Your doctor will ensure that you are adequately hydrated and will give you other medications to prevent this from happening.
• In case of severe allergic or hypersensitivity reactions, you must pay attention to reactions during perfusion after your first treatment cycle.
• At any time during or after treatment, inform your doctor immediately if you notice or someone notices in you: memory loss, cognitive difficulties, difficulty walking, or vision loss. These symptoms may be due to a rare but severe brain infection that can be fatal (progressive multifocal leukoencephalopathy or LMP).

Children and adolescents

There is no experience of use of bendamustine hydrochloride in children and adolescents.

Use of Bendamustina Glenmark with other medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may take any other medication.

If Bendamustina Glenmark is used in combination with medications that inhibit blood cell formation in the bone marrow, the effect on the bone marrow can be intensified.

If Bendamustina Glenmark 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 (e.g., viral vaccination).

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

Bendamustina Glenmark can cause genetic damage and has caused malformations in studies conducted on animals. It should not be used during pregnancy unless the 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 fertile woman, you must use effective contraceptive measures before and during treatment with Bendamustina Glenmark. If you become pregnant during treatment with Bendamustina Glenmark, you must inform your doctor immediately and seek genetic counseling.

Breastfeeding

Bendamustina Glenmark should not be administered during breastfeeding. If you need treatment with hydrochloride bendamustine during breastfeeding, you must suspend it.

Consult your doctor or pharmacist before using any medication.

Fertility

It is recommended that men treated with Bendamustina Glenmark do not father children during treatment or in the 6 months following treatment. Before starting treatment, you must be advised on sperm conservation, as there is a possibility that it may cause permanent sterility.

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

Driving and operating machines

Bendamustina Glenmark has a significant influence on your ability to drive and operate machines. Do not drive or operate 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. In case of doubt, consult your doctor or pharmacist again.

Bendamustina Glenmark is administered through 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 the determined levels.

Your doctor will measure these values periodically.

Chronic Lymphocytic Leukemia

Non-Hodgkin Lymphomas

Multiple Myeloma

Treatment will end if the white blood cell count (leukocytes) and/or platelet count falls below the determined levels. Treatment may be resumed when the leukocyte and platelet counts have increased.

Renal or Hepatic Insufficiency

Dosage adjustment may be necessary based on the degree of liver function deterioration (in 30% in case of moderate liver deterioration, your doctor may consider returning to the normal dose if well tolerated). No dosage adjustment is necessary in case of renal function alteration. Your doctor will decide if a dosage adjustment is necessary.

How to Administer

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

Your doctor will administer the prepared solution for infusion. The solution is administered through a vein as a brief infusion for 30 to 60 minutes.

Treatment Duration

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

If you are concerned or have any doubts about treatment with Bendamustina Glenmark, talk to your doctor or pharmacist.

If You Miss a Dose of BendamustinaGlenmark

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

If You Interrupt Treatment with BendamustinaGlenmark

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

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

Like all medicines, Bendamustina Glenmark may cause side effects, although not everyone will experience them. Some of the results listed below may be found after tests performed by your doctor.

To evaluate side effects, the following definitions are used, based on frequency:

Very common: may affect more than 1 in 10 people.

Common: may affect up to 1 in 10 people.

Uncommon: may affect up to 1 in 100 people.

Rare: may affect up to 1 in 1,000 people.

Very rare: may affect up to 1 in 10,000 people.

Not known: the frequency cannot be estimated from available data.

In very rare cases, tissue degradation (necrosis) has been observed after extravasation of bendamustina in the tissue surrounding blood vessels (extravascular). If the product leaks out of a vein, there may be a burning sensation at the site of the needle insertion. Consequences may include pain and skin healing problems.

The dose-limiting side effect of bendamustina is a change in bone marrow function, which usually normalizes. Suppression of bone marrow function may lead to a reduction in blood cell counts, which in turn may increase the risk of infection, anemia, or bleeding.

Very common (may affect more than 1 in 10 people):

• Reduction in white blood cell count (cells that fight diseases in your blood)
• Reduction in red blood cell pigment (hemoglobin: a protein in red blood cells that carries oxygen throughout the body)
• Reduction in platelet count (colorless blood cells that help blood clotting)
• Infections
• Nausea
• Vomiting
• Mucous membrane inflammation
• Headache
• Increased blood creatinine concentration (a chemical waste product produced by your muscle)
• Increased blood urea concentration (a chemical waste product)
• Fever
• Fatigue

Common (may affect up to 1 in 10 people):

• Bleeding (hemorrhage)
• Metabolic alteration caused by cancer cells dying, which release their contents into the bloodstream
• Decreased red blood cells, which may cause pale skin and weakness or difficulty breathing (anemia)
• Reduction in neutrophil count (a common type of white blood cell needed to fight infections)
• Hypersensitivity reactions, such as skin inflammation (dermatitis) or urticaria
• Elevation of liver enzymes AST/ALT (may indicate liver inflammation or damage)
• Increased alkaline phosphatase enzyme (an enzyme synthesized mainly in the liver and bones)
• Increased bilirubin pigment (a substance produced during the normal breakdown of red blood cells)
• Decreased potassium blood level (a nutrient necessary for nerve and muscle cell function, including the heart)
• Cardiac function alteration (disfunction)
• Cardiac rhythm alteration (arrhythmia)
• Elevation or decrease in blood pressure (hypotension or hypertension)
• Pulmonary function alteration
• Dyspepsia
• Constipation
• Mouth ulcers (stomatitis)
• Loss of appetite
• Hair loss
• Skin alterations
• Amenorrhea (absence of menstruation)
• Pain
• Insomnia
• Chills
• Dehydration
• Dizziness
• Itchy skin rash (urticaria)

Uncommon (may affect up to 1 in 100 people):

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

Rare (may affect up to 1 in 1,000 people):

• Blood infection (sepsis)
• Severe allergic and hypersensitivity reactions (anaphylactic reactions)
• Decreased bone marrow function, which may cause you to feel unwell or appear in your blood test results
• Reactions similar to anaphylactic reactions (anaphylactoid reactions)
• Drowsiness
• Loss of voice (aphonia)
• Acute circulatory failure (failure of the 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)
• Itchy skin rash (exanthema maculosa)
• Excessive sweating (hyperhidrosis)

Very rare (may affect up to 1 in 10,000 people):

• Atypical primary inflammation of the lungs (pneumonia)
• Destruction of red blood cells in the blood
• Rapid decrease in blood pressure, sometimes with skin reactions or rashes (anaphylactic shock)
• Alteration of taste
• Alteration of sensitivity (paresthesias)
• Discomfort and pain in the limbs (peripheral neuropathy)
• Severe condition that causes blockage of specific receptors in the nervous system
• Nervous system disorders Lack of coordination (ataxia)
• Brain inflammation (encephalitis)
• Increased heart rate (tachycardia)
• Vein inflammation (phlebitis)
• Pulmonary tissue formation (pulmonary fibrosis)
• Haemorrhagic inflammation of the throat (oesophagitis haemorrhagica)
• Gastric or intestinal bleeding
• Infertility
• Multi-organ failure

Not known: The frequency cannot be estimated from available data:

• Liver failure
• Kidney failure
• Irregular and often rapid heartbeats (atrial fibrillation)
• Widespread painful red or purple rashes and blisters and/or other lesions that begin to appear 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 exanthema in combination therapy with rituximab.
• Pneumonitis
• Alveolar pulmonary hemorrhage
• 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, bronchial carcinoma) after treatment with bendamustina. A clear relationship with bendamustina could not be determined.

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

Severe skin rash, including Stevens-Johnson syndrome and toxic epidermal necrolysis. This may appear as red spots with a target shape or circular patches on the trunk, often with blisters in the center, skin peeling, mouth ulcers, throat, nose, genital, and eye ulcers, and may be preceded by fever and flu-like symptoms.

Widespread skin rash, elevated body temperature, increased lymph node swelling, and involvement of other organs (drug reaction with eosinophilia and systemic symptoms known as DRESS or drug hypersensitivity syndrome).

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a side effect that does not appear in this leaflet. You can also report them directly through theSistema Español de Farmacovigilancia de Medicamentos de Uso Humano:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

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 expiration date is the last day of the month indicated.

Store the vial in the outer packaging to protect the contents from light.

Check the expiration period before opening or preparing the solution.

Solutions for infusion prepared according to the instructions indicated at the end of this leaflet are stable inpolyethylene bags at room temperature / 60% relative humidity for 3.5 hours and in the refrigerator between 2°C – 8°C for 2 days. Bendamustina Glenmark does not contain preservatives. The solution should not be used after this period of time.

It is the user's responsibility to maintain aseptic conditions.

Medicines should not be thrown away through the drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you do not need. In this way, you will help to protect the environment.

Composition of BendamustineGlenmark

The active ingredient ishydrochloride ofbendamustine.

1 vial contains 25 mg ofhydrochloride ofbendamustine

1 vial contains 100 mg ofhydrochloride ofbendamustine.

After reconstitution, 1 ml of concentrate contains 2.5 mg ofhydrochloride ofbendamustine.

The other component is mannitol.

Aspect of the product and contents of the package

Lyophilized powder of white or almost white color with a amber glass vial with a rubber stopper and aluminum cap.

A type I glass vial of 25 mlcontains 25 mg of hydrochloride of bendamustine and are presented in packages of 1.5, 10 and 20 vials.

A type I glass vial of 50 mlcontains 100 mg of hydrochloride of bendamustine and are presented in packages of 1 and 5 vials.

May only be marketed in some package sizes.

Holder of the marketing authorization

Glenmark Airznemittel GmBH

Industriestr. 31, Gröbenzell,

Germany

Responsible for manufacturing

Synthon Hispania SL

c/ Castelló no 1, Pol. Las Salinas, Sant Boi de Llobregat

08830 Barcelona

Spain

Synthon, s.r.o.

Brnenská 32/cp. 597

678 01 Blansko

Czech Republic

Further information can be requested regarding this medicinal product by addressing the local representative of the holder of the marketing authorization:

Viso Farmacéutica, S.L.U.

c/ Retama 7, 7ª Planta

28045 Madrid

Spain

This medicinal product has been authorized in the Member States of the EU under the following names:

Last review date of this leaflet: January 2024

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

--------------------------------------------------------------------------------------------------------------------

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

As with all similar cytotoxics, nursing staff and doctors must take extreme precautions of safety, due to the potential genotoxicity and carcinogenicity of the preparation. Avoid inhalation (inspiration) and contact with the skin and mucous membranes while handling Bendamustine Glenmark (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 isotonic saline solution (0.9%). If possible, it is recommended to work on a special safety workbench (laminar flow) with a disposable impermeable absorbent sheet. Contaminated items are cytostatic waste. Please follow national guidelines for the disposal of cytostatic material! Pregnant women in the healthcare staff should not work with cytotoxics.

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

1. Preparation of the concentrate

• First, dissolve a Bendamustine Glenmark vial containing 25 mg ofhydrochloride ofbendamustine in 10 ml, agitating it.

• First, dissolve a Bendamustine Glenmark vial containing 100 mg ofhydrochloride ofbendamustine in 40 ml, agitating it.

2. Preparation of the perfusion solution

• As soon as a clear solution is obtained (usually within 5 to 10 minutes), 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 perfusion or injection solutions. Bendamustine should not be mixed with other substances during perfusion.

3. Administration

• The solution is administered by intravenous infusion over 30-60 minutes.
• The vials are for single use.
• Unused products or waste must be disposed of in accordance with local requirements.

• If unintentionally injected into the tissue surrounding the blood vessels (extravasal injection), the perfusion will be stopped immediately. The needle will be withdrawn after a brief aspiration. The affected tissue area will then be cooled. The arm will be elevated. It is unclear whether the use of additional treatments (such as corticosteroids) is beneficial (see section 4).

Composition of BendamustineGlenmark

The active ingredient ishydrochloride ofbendamustine.

1 vial contains 25 mg ofhydrochloride ofbendamustine

1 vial contains 100 mg ofhydrochloride ofbendamustine.

After reconstitution, 1 ml of concentrate contains 2.5 mg ofhydrochloride ofbendamustine.

The other component is mannitol.

Aspect of the product and contents of the package

Lyophilized powder of white or almost white color with a amber glass vial with a rubber stopper and aluminum cap.

A type I glass vial of 25 mlcontains 25 mg of hydrochloride of bendamustine and are presented in packages of 1.5, 10 and 20 vials.

A type I glass vial of 50 mlcontains 100 mg of hydrochloride of bendamustine and are presented in packages of 1 and 5 vials.

May only be marketed in some package sizes.

Holder of the marketing authorization

Glenmark Airznemittel GmBH

Industriestr. 31, Gröbenzell,

Germany

Responsible for manufacturing

Synthon Hispania SL

c/ Castelló no 1, Pol. Las Salinas, Sant Boi de Llobregat

08830 Barcelona

Spain

Synthon, s.r.o.

Brnenská 32/cp. 597

678 01 Blansko

Czech Republic

Further information can be requested regarding this medicinal product by addressing the local representative of the holder of the marketing authorization:

Viso Farmacéutica, S.L.U.

c/ Retama 7, 7ª Planta

28045 Madrid

Spain

This medicinal product has been authorized in the Member States of the EU under the following names:

Last review date of this leaflet: January 2024

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

--------------------------------------------------------------------------------------------------------------------

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

As with all similar cytotoxics, nursing staff and doctors must take extreme precautions of safety, due to the potential genotoxicity and carcinogenicity of the preparation. Avoid inhalation (inspiration) and contact with the skin and mucous membranes while handling Bendamustine Glenmark (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 isotonic saline solution (0.9%). If possible, it is recommended to work on a special safety workbench (laminar flow) with a disposable impermeable absorbent sheet. Contaminated items are cytostatic waste. Please follow national guidelines for the disposal of cytostatic material! Pregnant women in the healthcare staff should not work with cytotoxics.

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

1. Preparation of the concentrate

• First, dissolve a Bendamustine Glenmark vial containing 25 mg ofhydrochloride ofbendamustine in 10 ml, agitating it.

• First, dissolve a Bendamustine Glenmark vial containing 100 mg ofhydrochloride ofbendamustine in 40 ml, agitating it.

2. Preparation of the perfusion solution

• As soon as a clear solution is obtained (usually within 5 to 10 minutes), 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 perfusion or injection solutions. Bendamustine should not be mixed with other substances during perfusion.

3. Administration

• The solution is administered by intravenous infusion over 30-60 minutes.
• The vials are for single use.
• Unused products or waste must be disposed of in accordance with local requirements.

If unintentionally injected into the tissue surrounding the blood vessels (extravasal injection), the perfusion will be stopped immediately. The needle will be withdrawn after a brief aspiration. The affected tissue area will then be cooled. The arm will be elevated. It is unclear whether the use of additional treatments (such as corticosteroids) is beneficial (see section 4).