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

Bendamustine hydrochloride

Read the entire leaflet carefully before you start using 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 and must not be given to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents:

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

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

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

Bendamustina Glenmark 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’s lymphomas that have not responded, or have responded only for a short period of time, to previous treatment with rituximab.

? Multiple myeloma, if treatments containing thalidomide or bortezomib are not suitable for you.

2. What you need to know before using Bendamustina Glenmark

Do not use Bendamustina Glenmark

• if you are allergic to bendamustine hydrochloride or to any of the other components of this medicine (listed in section 6).
• during breastfeeding; if treatment with Bendamustina Glenmark is necessary during breastfeeding, breastfeeding must be discontinued (see section Warnings and precautions)
• if you have severe hepatic dysfunction (damage to the functional liver 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 in the blood
• if you have undergone a major surgical procedure 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

Talk to your doctor before starting Bendamustina Glenmark

• if your bone marrow's ability to replace blood cells is reduced. White blood cell and platelet counts must be measured before starting treatment with Bendamustina Glenmark, before each treatment cycle, and during the intervals between cycles.
• if you have infections. If you experience signs of infection such as fever or pulmonary symptoms, contact your doctor.
• if you develop skin reactions during treatment with Bendamustina Glenmark. Reactions may increase in intensity.
• if you develop widespread, painful red or purple rashes and blisters and/or other lesions starting in the mucous membranes (e.g., mouth and lips), particularly if you have previously had photosensitivity, respiratory tract 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 in one side or observe blood in your urine or reduced urine output. If your condition is very severe, your body may be unable to eliminate all waste products from dying cancer cells. This is called tumor lysis syndrome and may lead to kidney failure and heart problems within 48 hours after the first dose of Bendamustina Glenmark. Your doctor will ensure you are adequately hydrated and will give you other medications to prevent this from occurring.
• in case of severe allergic or hypersensitivity reactions, you should be vigilant for infusion-related reactions after your first treatment cycle.
• at any time during or after treatment, inform your doctor immediately if you or someone else notices: memory loss, cognitive difficulties, difficulty walking, or vision loss. These symptoms may be due to a very rare but serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML).

Children and adolescents

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

Use of Bendamustina Glenmark 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 Glenmark is used in combination with medicines that suppress bone marrow blood cell formation, the effect on the bone marrow may be intensified.

If Bendamustina Glenmark 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 or pharmacist before using this medicine.

Pregnancy

Bendamustina Glenmark may cause genetic damage and has caused malformations in animal studies. It must not be used during pregnancy unless clearly considered necessary 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 Bendamustina Glenmark. If you become pregnant during treatment with Bendamustina Glenmark, you must inform your doctor immediately and seek genetic counseling.

Breastfeeding

Bendamustina Glenmark must not be administered during breastfeeding. If treatment with bendamustine hydrochloride is required during breastfeeding, breastfeeding must be discontinued.

Consult your doctor or pharmacist before using any medicine.

Fertility

Men treated with Bendamustina Glenmark are advised not to father a child during treatment and for 6 months after treatment. Before starting treatment, you should seek advice on sperm preservation, as treatment may cause permanent sterility.

If you are a man, you must not father a child 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 wish to seek advice on sperm preservation before starting treatment.

Driving and use of machines

Bendamustina Glenmark 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 Glenmark

Follow exactly the administration instructions for this medicine provided by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

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

You must not start treatment if your white blood cell (leukocyte) and/or platelet counts are below certain determined levels.

Your doctor will measure these values periodically.

Chronic lymphocytic leukemia

Non-Hodgkin Lymphomas

Multiple myeloma

Treatment will be discontinued if white blood cell (leukocyte) and/or platelet counts fall below predetermined levels. Treatment may be resumed once leukocyte and platelet counts have increased.

Renal or hepatic impairment

Dosage adjustment may be necessary depending on the degree of liver function impairment (a 30% dose reduction in case of moderate liver impairment; if well tolerated, your doctor may consider returning to the normal dose). Dose adjustment is not necessary in case of renal function impairment. Your doctor will decide whether a dose adjustment is needed.

How it is administered

Bendamustina Glenmark must only be administered by physicians experienced in the treatment of tumors. Your doctor will administer the exact dose of Bendamustina Glenmark 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

There is no defined duration for treatment with Bendamustina Glenmark. The duration of treatment depends on the disease and the response to treatment.

If you have any concerns or questions about treatment with Bendamustina Glenmark, speak with your doctor or pharmacist.

If you forget to use Bendamustina Glenmark

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

If you interrupt treatment with Bendamustina Glenmark

Your doctor will decide whether treatment should be interrupted or whether another treatment 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, Bendamustina Glenmark may cause adverse effects, although not everyone experiences them. Some of the events listed below may be detected through tests performed by your doctor.

To classify adverse effects, the following frequency definitions are used:

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: cannot be estimated from the available data.

In very rare cases, tissue damage (necrosis) has been observed following extravasation of bendamustine into the surrounding tissue outside blood vessels (extravascular). If the drug leaks out of the vein, a burning sensation may occur at the injection site. Consequences may include pain and impaired skin healing.

The dose-limiting adverse effect of bendamustine is bone marrow dysfunction, which usually resolves. Suppression of bone marrow function may lead to reduced blood cell counts, thereby increasing the risk of infection, anemia, or bleeding.

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

• Decrease in white blood cell count (cells that fight disease in your blood)
• Decrease in red blood pigment (hemoglobin: a protein in red blood cells that carries oxygen throughout the body)
• Decrease in platelet count (colorless blood cells that help blood clotting)
• Infections
• Nausea
• Vomiting
• Inflammation of mucous membranes
• Headache
• Increased blood creatinine concentration (a chemical waste product produced by your muscles)
• Increased blood urea concentration (a chemical waste product)
• Fever
• Fatigue

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

• Bleeding (hemorrhage)
• Metabolic disturbance caused by dying cancer cells releasing their contents into the bloodstream
• Decrease in red blood cells, which may cause pale skin, weakness, or difficulty breathing (anemia)
• Decrease in neutrophil count (a common type of white blood cell needed to fight infections)
• Hypersensitivity reactions, such as allergic skin inflammation (dermatitis) or hives
• Increased liver enzymes AST/ALT (may indicate inflammation or damage to liver cells)
• Increased alkaline phosphatase enzyme (an enzyme mainly produced in the liver and bones)
• Increased bile pigment (a substance produced during normal breakdown of red blood cells)
• Low blood potassium levels (a nutrient necessary for nerve and muscle cell function, including in the heart)
• Impaired heart function (cardiac dysfunction)
• Irregular heart rhythm (arrhythmia)
• Increase or decrease in blood pressure (hypotension or hypertension)
• Impaired lung function
• Diarrhea
• Constipation
• Mouth ulcers (stomatitis)
• Loss of appetite
• Hair loss
• Skin disorders
• Absence of menstrual periods (amenorrhea)
• Pain
• Insomnia
• Chills
• Dehydration
• Dizziness
• Itchy skin rash (urticaria)

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

• Fluid accumulation in the sac surrounding the heart (fluid leakage into the pericardial space)
• Ineffective production of all blood cells in the bone marrow (spongy tissue inside bones where blood cells are formed)
• Acute leukemia
• Heart attack, 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 make you feel unwell or show up in blood tests
• Symptoms similar to anaphylactic reactions (anaphylactoid reactions)
• Drowsiness
• Loss of voice (aphonia)
• Acute circulatory failure (failure of blood circulation, primarily of cardiac origin, leading to inability to maintain oxygen and nutrient supply to tissues and toxin removal)
• Skin redness (erythema)
• Skin inflammation (dermatitis)
• Itching (pruritus)
• Skin rash (maculopapular exanthema)
• Excessive sweating (hyperhidrosis)

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

• Primary atypical lung inflammation (pneumonia)
• Destruction of red blood cells
• Rapid drop in blood pressure, sometimes with skin reactions or rashes (anaphylactic shock)
• Altered sense of taste
• Altered sensation (paresthesia)
• Discomfort and pain in limbs (peripheral neuropathy)
• Serious condition causing blockage of specific receptors in the nervous system
• Nervous system disorders: lack of coordination (ataxia)
• Brain inflammation (encephalitis)
• Increased heart rate (tachycardia)
• Inflammation of veins (phlebitis)
• Tissue formation in the lungs (lung fibrosis)
• Hemorrhagic inflammation of the throat (hemorrhagic esophagitis)
• Gastric or intestinal bleeding
• Infertility
• Multi-organ failure

Not known: frequency cannot be estimated from available data:

• Liver failure
• Kidney failure
• Irregular and often rapid heartbeats (atrial fibrillation)
• Widespread, painful red or purple rash with blisters and/or other lesions starting in mucous membranes (e.g., mouth and lips), particularly if there has been prior sensitivity to light, respiratory tract infections (e.g., bronchitis), and/or fever
• Drug rash during combination therapy with rituximab
• Pneumonitis
• Alveolar pulmonary hemorrhage
• 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, bronchial carcinoma) following treatment with bendamustine. A clear relationship with bendamustine could not be established.

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

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

Widespread skin rashes, high body temperature, swollen lymph nodes, and involvement of other organs (drug reaction with eosinophilia and systemic symptoms, known as DRESS or drug hypersensitivity syndrome).

Reporting of adverse effects

If you experience any adverse effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Bendamustina Glenmark

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 expiry date refers to the last day of the month indicated.

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

Check the expiry date before opening or preparing the solution.

The infusion solutions prepared according to the instructions provided at the end of this leaflet are stable in polyethylene 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. Therefore, the solution should not be used after this period.

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

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the container and other information

Composition of BendamustineGlenmark

The active substance is bendamustine hydrochloride.

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

After reconstitution, 1 ml of concentrate contains 2.5 mg of bendamustine hydrochloride.

The other component is mannitol.

Appearance of the product and contents of the pack

A white or almost white lyophilized powder in an amber glass vial with a rubber stopper and an aluminium flip-off cap.

A type I glass vial of 25 ml contains 25 mg of bendamustine hydrochloride and is available in packs containing 1, 5, 10 and 20 vials.

A type I glass vial of 50 ml contains 100 mg of bendamustine hydrochloride and is available in packs containing 1 and 5 vials.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Glenmark Arzneimittel GmbH
Industriestr. 31
82194 Gröbenzell
Germany

Manufacturer:

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

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Glenmark Farmacéutica, S.L.U.
C/ Retama 7, 7th floor
28045 Madrid
Spain

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

Date of the most recent review of this summary: January 2024

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

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This information is intended exclusively for doctors or healthcare professionals:

As with all similar cytotoxic agents, nursing staff and physicians must take extreme safety precautions due to the potential genotoxic and carcinogenic properties of this preparation. Avoid inhalation (inspiration) and contact with skin and mucous membranes when handling Bendamustina Glenmark (wear gloves, protective clothing, and, if possible, a mask!). If any part of the body becomes contaminated, carefully clean it with soap and water, and rinse the eyes with 0.9% saline solution (isotonic). If possible, it is recommended to work on a special safety workbench (laminar flow hood) with a disposable, liquid-proof absorbent pad. Contaminated materials are cytostatic waste. Please follow national regulations regarding the disposal of cytostatic material! Pregnant female staff members must not handle cytostatics.

The ready-to-use solution must be prepared by dissolving the contents of one vial of Bendamustina Glenmark exclusively in water for injection, as follows:

1. Preparation of the concentrate
   • First, dissolve a vial of Bendamustina Glenmark containing 25 mg of bendamustine hydrochloride in 10 ml by agitation.

• First, dissolve a vial of Bendamustina Glenmark containing 100 mg of bendamustine hydrochloride in 40 ml by agitation.

2. Preparation of the infusion solution

   • Immediately after obtaining a clear solution (usually within 5 to 10 minutes), dissolve the total recommended dose of bendamustine in 0.9% saline solution (isotonic) 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.
   • Unused products or waste must be disposed of according to local requirements.

• If the product is accidentally injected into the tissue surrounding blood vessels (extravasation), infusion must be stopped immediately. The needle will be withdrawn after brief aspiration. The affected tissue area should then be cooled. The arm should be elevated. It is unclear whether additional treatments (such as corticosteroids) are beneficial (see section 4).

Composition of Bendamustina Glenmark

The active substance is bendamustine hydrochloride.

One vial contains 25 mg of bendamustine hydrochloride.

One vial contains 100 mg of bendamustine hydrochloride.

After reconstitution, 1 ml of concentrate contains 2.5 mg of bendamustine hydrochloride.

The other component is mannitol.

Presentation of the product and contents of the container

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

A type I 25 ml glass vial contains 25 mg of bendamustine hydrochloride and is available in pack sizes of 1, 5, 10 and 20 vials.

A type I 50 ml glass vial contains 100 mg of bendamustine hydrochloride and is available in pack sizes of 1 and 5 vials.

Only certain pack sizes may be marketed.

Marketing Authorization Holder

Glenmark Airznemittel GmbH

Industriestr. 31, Gröbenzell,

Germany

Manufacturer

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

For further information about this medicine, please contact the local representative of the Marketing Authorization Holder:

Viso Farmacéutica, S.L.U.

c/ Retama 7, 7th Floor

28045 Madrid

Spain

This medicine has been authorized in EU Member States under the following names:

Date of the most recent review of this leaflet: January 2024

Updated and detailed information on this medicine 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 safety precautions due to the potential genotoxic and carcinogenic properties of this preparation. Avoid inhalation and contact with skin and mucous membranes when handling Bendamustina Glenmark (wear gloves, protective clothing, and, if possible, a mask!). If any part of the body becomes contaminated, wash carefully with soap and water, and rinse eyes with 0.9% isotonic saline solution. Whenever possible, it is recommended to work on a special safety workbench (laminar flow hood) using a liquid-impermeable disposable absorbent sheet. Contaminated materials are cytostatic waste. Please follow national regulations regarding the disposal of cytostatic material! Pregnant female staff members should not handle cytostatics.

The ready-to-use solution should be prepared by dissolving the contents of one vial of Bendamustina Glenmark exclusively in water for injection, as follows:

1. Preparation of the concentrate
   • First, dissolve the contents of one vial of Bendamustina Glenmark containing 25 mg of bendamustine hydrochloride in 10 ml, by agitation.

• First, dissolve the contents of one vial of Bendamustina Glenmark containing 100 mg of bendamustine hydrochloride in 40 ml, by agitation.

2. Preparation of the infusion solution

   • Immediately after obtaining a clear solution (usually within 5 to 10 minutes), 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.
   • Unused products or waste must be disposed of in accordance with local requirements.

If the product is accidentally injected into the tissue surrounding blood vessels (extravasation), infusion must be stopped immediately. The needle will be withdrawn after brief aspiration. The affected tissue area should then be cooled and the arm elevated. It is unclear whether additional treatments (such as corticosteroids) are beneficial (see section 4).