Prospect: information for the user

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

Bendamustine hydrochloride

Read this prospect carefully before starting to use this 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 you must not give it 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 do not appear in this prospect. See section 4.

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

Bendamustina Kabi 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 thalidomide or bortezomib are not suitable for you.

No use Bendamustina Kabi

• if you are allergic to hydrochloride bendamustine or to any of the other components of this medication (listed in section 6).
• during breastfeeding; if treatment with bedamustina hydrochloride is necessary during breastfeeding, you must discontinue breastfeeding (see section Pregnancy, breastfeeding and fertility).
• if you have severe liver dysfunction (liver cell damage);
• if you have yellow discoloration of the skin or the white of the eyes caused by liver or blood problems (jaundice);
• if you have a severe bone marrow disorder (bone marrow depression) and severe alterations in the number of white blood cells and platelets in the blood;
• if you have undergone major surgery within 30 days of starting treatment;
• if you have had any infection, especially if accompanied by a reduction in the number of white blood cells (leucocytopenia).
• in combination with yellow fever vaccines.

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting to use Bendamustina Kabi

• if your bone marrow has been reduced in its ability to replace blood cells. You must have your white blood cell and platelet count measured in the blood before starting treatment with Bendamustina Kabi, before each treatment cycle and at intervals between cycles.
• in case of infections. If you experience signs of infection, such as fever or respiratory symptoms, you must contact your doctor.
• Inform your doctor immediately if, at any time during treatment, during or after, you notice or someone notices in you: memory loss, difficulty thinking, difficulty walking or loss of vision; this may be due to a rare but serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML).
• if you experience skin reactions during treatment with Bendamustina Kabi. Skin reactions may increase in intensity.
• Inform your doctor if you notice any suspicious changes in your skin because you may have a higher risk of certain types of skin cancer (non-melanoma skin cancer) with the use of this medication.
• in case of red or purple painful rash that spreads and forms blisters and/or other lesions on mucous membranes (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 may not be able to eliminate all the waste products of dying cancer cells. This is called tumour lysis syndrome and may cause kidney failure and heart problems within 48 hours of the first dose of Bendamustina Kabi. Your doctor may need to ensure that you are adequately hydrated and give you other medications to prevent this from happening.
• in case of severe allergic or hypersensitivity reactions, you must pay attention to reactions to infusion after your first treatment cycle.

Use of Bendamustina Kabi and other medications

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

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

If bendamustina hydrochloride is usedin combination with medications that alter the immune response, this effect may be intensified.

Cytostatic medications may reduce the effectiveness of some live virus vaccines.

Additionally, cytostatic medications 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 or plan to become pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

Bendamustine hydrochloride may cause genetic damage and has caused malformations in studies conducted on animals. Bendamustina Kabi should not be used during pregnancy unless your doctor considers it clearly necessary. If you receive this treatment, you must ask a doctor to explain the risk of possible adverse effects of the treatment for your child. 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 age must use effective contraceptive methods during treatment and for 6 months after the last dose of Bendamustina Kabi.

Breastfeeding

Bendamustina Kabi should not be administered during breastfeeding. If you need 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 the end of treatment must seek advice on sperm conservation before treatment begins.

Women:

Female patients who wish to have children after the end of treatment must consult their doctor.

Driving and operating machinery

Bendamustine hydrochloride affects 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.

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 Kabi 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 certain 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) is below certain levels. Treatment may be resumed when the leukocyte and platelet counts have increased.

Renal or Hepatic Insufficiency

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

How to Administer

Bendamustina Kabi treatment can only be administered by experienced oncologists. Your healthcare professional will administer the exact dose of Bendamustina Kabi and take the necessary precautions.

Your healthcare professional 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 Bendamustina Kabi treatment has not been defined. Treatment duration depends on the disease and response to treatment.

If you are concerned or have any doubts about Bendamustina Kabi treatment, talk to your doctor or nurse.

If You Forget to Use Bendamustina Kabi

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

If You Interrupt Bendamustina Kabi Treatment

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

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Some of the findings listed below may be found after tests performed by your doctor.

In very rare cases, tissue decomposition (necrosis) has been observed after the extravasation of Bendamustina Kabi 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. The consequences may be pain and skin healing problems.

The dose-limiting side effect of Bendamustina Kabi is a change in bone marrow function, which usually normalizes. Bone marrow suppression can lead to low blood cell counts, which in turn can increase the risk of infection, anemia, or high risk of bleeding.

Very common (may affect more than 1 in 10 patients)

• Reduction in white blood cell count (cells that fight diseases in the 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 to clot)
• Infections
• Uncomfort (nausea)
• Vomiting
• Mucous membrane inflammation
• 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 disorder caused by cancer cells dying, which release their contents into the circulatory system
• Decreased red blood cells, which can cause pale skin and cause weakness or difficulty breathing (anemia)
• Reduced neutrophil count (a common type of white blood cell important for fighting infections)
• Hypersensitivity reactions, such as skin inflammation (dermatitis) or urticaria
• Elevated liver enzymes AST/ALT (which may indicate inflammation or liver cell damage)
• Increased alkaline phosphatase enzyme (an enzyme primarily produced in the liver and bones)
• Increased bilirubin pigment (a substance generated during the normal breakdown of red blood cells)
• Low potassium blood level (a nutrient necessary for nerve and muscle cell function, including the heart)
• Cardiac function alteration (dysfunction), such as feeling the heartbeat (palpitations) or chest pain (angina pectoris)
• Cardiac rhythm alteration (arrhythmia)
• Increased or decreased blood pressure (hypotension or hypertension)
• Pulmonary function alteration
• Diarrhea
• 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 patients)

• Accumulation of fluid in the sac surrounding the heart (pericardial effusion)
• Ineffective production of blood cells in bone marrow (the spongy tissue inside bones where blood cells are produced)
• Acute leukemia
• Myocardial infarction, 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)
• Bone marrow function decrease, which may cause discomfort or appear in blood tests
• Reactions similar to anaphylactic reactions (anaphylactoid reactions)
• Drowsiness
• Loss of voice (aphonia)
• Acute circulatory failure (circulatory failure primarily of cardiac origin with insufficient supply of oxygen and other nutrients to tissues and removal 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 patients)

• Atypical primary inflammation of the lungs (pneumonia)
• Destruction of red blood cells in the blood
• Rapid decrease in blood pressure, sometimes with skin reactions (anaphylactic shock)
• Alteration of taste
• Alteration of sensitivity (paresthesias)
• Discomfort and pain in the limbs (peripheral neuropathy)
• Severe condition resulting from 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 hemorrhage
• Infertility
• Multi-organ failure

Frequency not known (frequency cannot be estimated from available data)

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

Cases of tumors (myelodysplastic syndromes, acute myeloid leukemia, bronchial carcinoma) have been reported after treatment with hydrochloride bendamustine. A clear relationship with hydrochloride bendamustine could not be determined.

Consult 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 red spots with a target-like appearance, 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, high body temperature, lymph node enlargement, and involvement of other organs (drug reaction with eosinophilia and systemic symptoms, also known as DRESS or drug hypersensitivity syndrome).

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

Reporting of adverse reactions

If you experience any side effects, consult your doctor, hospital pharmacist, or nurse, even if they are side effects not listed in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicinal Products for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the vial and on the packaging after CAD. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Check the validity period before opening or preparing the solution

Correctly prepared infusion solutions according to the instructions included 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. Bendamustina Kabi does not contain preservatives. Therefore, the solution should not be used after these periods.

From a microbiological point of view, the solution should be used immediately. If not used immediately, the storage times and conditions in use 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 in controlled and validated aseptic conditions.

Do not use this medication if you observe visible signs of deterioration.

Medications should not be disposed of through 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 Bendamustina Kabi

• The active ingredient is bendamustine hydrochloride.

1 vial contains 25 mg of bendamustina hydrochloride.

1 vial contains 100 mg of bendamustina hydrochloride.

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

• The other component is mannitol.

Appearance of the product and contents of the package

Glass vials of topaz color with rubber stopper and sealed with an aluminum flip-off cap of green or blue color. The powder is a white or almost white lyophilized tablet.

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

Only some package sizes may be marketed.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder

Fresenius Kabi España S.A.U.

Torre Mapfre – Vila Olímpica

Marina 16-18

08005 Barcelona

Spain

Responsible manufacturer

FFresenius Kabi Deutschland GmbH

Pfingstweide 53

61169 Friedberg

Germany

Last review date of this leaflet: May 2024

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

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This information is intended solely for healthcare professionals:

As with all similar cytotoxics, healthcare personnel and doctors must exercise extreme caution due to the potential genotoxicity and carcinogenicity of the preparation. Avoid inhalation (respiration) and contact with the skin and mucous membranes while handling Bendamustina Kabi (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 9 mg/ml (0.9%) saline solution (isotonic). If possible, it is recommended to work on a special safety workbench (laminar flow) with a disposable impermeable liquid-proof sheet. Contaminated items are cytostatic waste. Please follow national guidelines for the disposal of cytostatic material. Female personnel who are pregnant should not work with cytotoxics.

The vials are for single use.

The ready-to-use solution must be prepared by dissolving the contents of a Bendamustina Kabi vial exclusively in water for injection preparations, as indicated below:

1. Concentrate preparation

• First, dissolve a Bendamustina Kabi vial containing 25 mg of bendamustina hydrochloride in 10 ml, agitating it.
• First, dissolve a Bendamustina Kabi vial containing 100 mg of bendamustina hydrochloride 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 Bendamustina Kabi in 9 mg/ml (0.9%) saline solution (isotonic) to obtain a final volume of approximately 500 ml. Bendamustina Kabi should not be dissolved with other perfusion or injection solutions. Bendamustina Kabi should not be mixed with other substances in perfusion.

3. Administration

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

The vials are for single use.

Any remaining medication or waste must be disposed of in accordance with local regulations.If the product is accidentally injected into the tissue surrounding the blood vessels (extravasal injection), the perfusion will be stopped immediately. The needle will be removed 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).