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

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Bendamustina Kabi 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, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should 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 effects, consult your doctor, pharmacist or nurse, even if these effects are not listed in this leaflet. See section 4.

Contents of the leaflet

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

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

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

Bendamustina Kabi 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 Kabi

Do not use Bendamustina Kabi

• 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 bendamustine hydrochloride is necessary during breastfeeding, you must discontinue breastfeeding (see section Pregnancy, breastfeeding, and fertility).
• if you have severe liver 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 the number of white blood cells and platelets in the blood;
• if you have undergone major surgery within the previous 30 days before starting treatment;
• if you have had any infection, especially if it was accompanied by a reduction in the number of white blood cells (leucopenia).
• in combination with yellow fever vaccines.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting treatment with Bendamustina Kabi

• 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 Kabi, before each treatment cycle, and during the intervals between cycles.
• if you have infections. If you experience signs of infection, such as fever or respiratory symptoms, contact your doctor.
• Inform your doctor immediately if, at any time during, while, or after treatment, you or someone else notices in you: 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).
• if you develop skin reactions during treatment with Bendamustina Kabi. Skin reactions may increase in severity.
• Contact your doctor if you notice any suspicious changes in your skin, as there may be an increased risk of certain types of skin cancer (non-melanoma skin cancer) with the use of this medicine.
• if you develop a painful red or purple rash that spreads and blisters form and/or other lesions on mucous membranes (e.g., mouth and lips), particularly if you have previously had light sensitivity, respiratory tract infections (e.g., bronchitis), and/or fever.
• if you have a heart condition (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 Kabi. Your doctor may need to ensure you are adequately hydrated and may give you additional medications to prevent this from occurring.
• in case of severe allergic or hypersensitivity reactions, you should be alert for infusion reactions after your first treatment cycle.

Use of Bendamustina Kabi and other medicines

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

If bendamustine hydrochloride is used in combination with medicines that inhibit blood cell formation in the bone marrow, the effect on the bone marrow may be intensified.

If bendamustine hydrochloride is used in combination with medicines that alter immune response, this effect may be intensified.

Cytostatic medicines may reduce the effectiveness of certain live virus vaccines.

Additionally, cytostatic medicines increase the risk of infection following vaccination with live 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

Bendamustine hydrochloride may cause genetic damage and has caused birth defects in animal studies. Bendamustina Kabi 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. Genetic counseling is recommended.

If you become pregnant during treatment with Bendamustina Kabi, you must inform your doctor immediately and seek genetic counseling.

Pregnancy precautions for men and women

Men:

Men undergoing treatment with Bendamustina Kabi must avoid fathering a child during treatment with Bendamustina Kabi and for 3 months after treatment has ended.

Women:

Women of childbearing potential must use effective contraception during treatment and for 6 months after the last dose of Bendamustina Kabi.

Breastfeeding

Bendamustina Kabi must not be administered during breastfeeding. If you require treatment with Bendamustina Kabi during breastfeeding, you must discontinue breastfeeding.

Fertility

Men:

There is a risk that treatment with Bendamustina Kabi may lead to infertility in men. Male patients who wish to have children after completion of treatment should seek advice on sperm preservation before treatment begins.

Women:

Patients who wish to have children after completion of treatment should consult their doctor.

Driving and use of machines

Bendamustine hydrochloride may affect your ability to drive or operate machinery. Do not drive or operate machinery if you experience adverse effects such as dizziness or lack of coordination.

3. How to use Bendamustina Kabi

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

Bendamustina Kabi is administered into a vein 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 (leukocyte) count and/or platelet count is below certain levels.

Your doctor will periodically measure these values.

Chronic lymphocytic leukemia

Non-Hodgkin lymphomas

Multiple myeloma

The treatment will be discontinued if the white blood cell (leukocyte) count falls below certain levels. Treatment may be resumed once the leukocyte and platelet counts have increased.

Renal or hepatic impairment

Dosage adjustment may be necessary depending on the degree of liver function impairment (an initial 30% reduction in dose in case of moderate liver impairment). No dose adjustment is required in case of kidney function impairment. Your doctor will decide whether a dose adjustment is necessary.

How it is administered

Treatment with Bendamustina Kabi must only be administered by physicians experienced in the treatment of tumors. Your healthcare professional will administer the exact dose of Bendamustina Kabi and take the necessary precautions.

Your healthcare professional 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 Kabi has not been defined. The duration of treatment depends on the disease and the response to therapy.

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

If you forget to use Bendamustina Kabi

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

If you interrupt treatment with Bendamustina Kabi

Your doctor will decide whether treatment should be interrupted or whether a different 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, this medicine can cause adverse effects, although not everyone will experience them.

Some of the findings listed below may be detected through tests performed by your doctor.

In very rare cases, tissue breakdown (necrosis) has been observed following extravasation of Bendamustina Kabi into the surrounding tissue of blood vessels (extravascular). If the product leaks outside a blood vessel, a burning sensation may occur at the needle insertion site. Consequences may include pain and impaired skin healing.

The dose-limiting adverse effect of Bendamustina Kabi is bone marrow dysfunction, which usually resolves. 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 (may affect more than 1 in 10 patients)

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

Common (may affect up to 1 in 10 patients)

• 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 and lead to weakness or difficulty breathing (anemia)
• Reduced neutrophil count (a common type of white blood cell important for fighting infections)
• Hypersensitivity reactions, such as allergic skin inflammation (dermatitis) or hives
• Increased liver enzymes AST/ALT (which 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 generated during the normal breakdown of red blood cells)
• Low blood potassium levels (a nutrient necessary for nerve and muscle cell function, including those of the heart)
• Cardiac dysfunction (e.g., awareness of heartbeat [palpitations] or chest pain [angina])
• Heart rhythm disturbances (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 patients)

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

Rare (may affect up to 1 in 1,000 patients)

• Blood infection (sepsis)
• Severe allergic and hypersensitivity reactions (anaphylactic reactions)
• Decreased bone marrow function, which may make you feel unwell or appear 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, resulting in insufficient delivery of oxygen and nutrients to tissues and inadequate removal of toxins)
• Redness of the skin (erythema)
• Skin inflammation (dermatitis)
• Itching (pruritus)
• Skin rash (macular exanthema)
• Excessive sweating (hyperhidrosis)

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

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

Frequency not known (cannot be estimated from available data)

• Liver failure
• Kidney failure
• Irregular and often rapid heart rhythm (atrial fibrillation)
• Painful red or purple rash that spreads and forms blisters and/or other lesions on mucous membranes (e.g., mouth and lips), particularly if you have previously had light sensitivity, respiratory tract infections (e.g., bronchitis), and/or fever
• Drug rash during combination treatment with rituximab
• Pneumonitis
• Lung bleeding
• Excessive urination, even at night, and excessive thirst even after drinking fluids (nephrogenic diabetes insipidus)

Cases of tumors (myelodysplastic syndromes, acute myeloid leukemia, bronchial carcinoma) have been reported after treatment with bendamustine hydrochloride. A clear relationship with bendamustine hydrochloride 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 rashes 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 rash, high body temperature, swollen lymph nodes, and involvement of other organs (drug reaction with eosinophilia and systemic symptoms, also known as DRESS or drug hypersensitivity syndrome).

If any of the adverse effects worsen or if you experience adverse effects not listed in this leaflet, please inform your doctor.

Reporting of adverse effects

If you experience any adverse effects, consult your doctor, hospital 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 Bendamustine Kabi

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

Do not use this medicine after the expiry date stated on the vial and on the outer packaging following EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

Check the shelf life before opening or preparing the solution.

Infusion solutions prepared correctly 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 for 2 days. Bendamustine Kabi does not contain preservatives. Therefore, the solution should not be used beyond these time limits.

From a microbiological standpoint, the solution 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 and 8°C, unless reconstitution/dilution has taken place under controlled and validated aseptic conditions.

Do not use this medicine if you notice any visible signs of deterioration.

Medicines must 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 Bendamustina Kabi

• 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 container

Topaz-coloured glass vials with a rubber stopper and sealed with a green or blue flip-off aluminium cap. The powder is a white or almost white lyophilized cake or powder.

Bendamustina Kabi is available in packs containing 1, 5, 10 and 20 vials with 25 mg of bendamustine hydrochloride, and 1 and 5 vials with 100 mg of bendamustine hydrochloride.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Fresenius Kabi España S.A.U.
Torre Mapfre – Vila Olímpica
Marina 16-18
08005 Barcelona
Spain

Manufacturer

Fresenius Kabi Deutschland GmbH
Pfingstweide 53
61169 Friedberg
Germany

Date of the most recent revision of this summary: May 2024

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 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 Kabi (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 9 mg/ml (0.9%) saline solution (isotonic). Whenever possible, it is recommended to work on a special safety workbench (laminar flow hood) using a disposable, liquid-impermeable absorbent pad. Contaminated materials are cytostatic waste. Please follow national regulations regarding the disposal of cytostatic materials. Pregnant female staff members should not handle cytostatics.

The vials are for single use only.

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

1. Preparation of the concentrate

   • First, dissolve one vial of Bendamustina Kabi containing 25 mg of bendamustine hydrochloride in 10 ml, by agitation.
   • First, dissolve one vial of Bendamustina Kabi 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 total recommended dose of Bendamustina Kabi in 0.9% saline solution (9 mg/ml, isotonic) to achieve a final volume of approximately 500 ml. Bendamustina Kabi must not be dissolved in other infusion or injection solutions. Bendamustina Kabi 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 medicinal product or waste material must be disposed of in accordance with local regulations. If the product is accidentally injected into the surrounding tissue (extravasation), the 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).