Bendamustine Kabi

Package Leaflet: Information for the User

Bendamustine Kabi, 2.5 mg/mL, Powder for Concentrate for Solution for Infusion

Bendamustine Hydrochloride

Read the Package Leaflet Carefully Before Using the Medication, as it Contains Important Information for the Patient.

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Keep this package leaflet, so you can read it again if you need to.
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In case of any doubts, consult a doctor or pharmacist.
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This medication has been prescribed specifically for you. Do not pass it on to others. The medication may harm another person, even if their symptoms are the same as yours.
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If the patient experiences any side effects, including those not listed in this package leaflet, they should inform their doctor, pharmacist, or nurse. See section 4.

Package Leaflet Contents

• 1. What is Bendamustine Kabi and What is it Used For
• 2. Important Information Before Using Bendamustine Kabi
• 3. How to Use Bendamustine Kabi
• 4. Possible Side Effects
• 5. How to Store Bendamustine Kabi
• 6. Package Contents and Other Information

1. What is Bendamustine Kabi and What is it Used For

Bendamustine Kabi is a medication used to treat certain types of cancer (cytostatic medication).
Bendamustine Kabi is used as a single medication (monotherapy) or in combination with other medications to treat the following types of cancer:

• Chronic lymphocytic leukemia when fludarabine-containing chemotherapy is not indicated;
• Non-Hodgkin's lymphoma that has not responded or has responded too briefly to previous rituximab treatment;
• Multiple myeloma when talidomide or bortezomib-containing chemotherapy is not indicated.

2. Important Information Before Using Bendamustine Kabi

When Not to Use Bendamustine Kabi:

• If the patient has been diagnosed with hypersensitivity (allergy) to bendamustine or any other component of the medication (listed in section 6);
• During breastfeeding, as bendamustine treatment requires cessation of breastfeeding (see section on Pregnancy, Breastfeeding, and Fertility);
• If the patient has severe liver damage (liver cell dysfunction);
• If the patient has jaundice (yellowing of the skin or whites of the eyes) due to liver or blood disorders;
• If the patient has severe bone marrow dysfunction (bone marrow suppression) and significant changes in white blood cell and platelet counts;
• If the patient has had major surgery within 30 days before starting treatment;
• If the patient has an infection, especially with accompanying low white blood cell count (leukopenia);
• If the patient has been vaccinated against yellow fever.

Warnings and Precautions

Before starting Bendamustine Kabi treatment, discuss the following with your doctor, pharmacist, or nurse:

• In cases of reduced bone marrow function. The white blood cell and platelet counts should be checked before starting Bendamustine Kabi treatment, before each subsequent treatment cycle, and during treatment intervals.
• In cases of infection. Contact your doctor if you experience infection symptoms, including fever and respiratory symptoms.
• If any of the following symptoms occur during or after treatment: memory loss, thinking problems, difficulty walking, or vision loss - these may be caused by a rare but serious brain infection (progressive multifocal leukoencephalopathy, PML), which can lead to death. Inform your doctor immediately.
• In cases of skin changes during Bendamustine Kabi treatment. Skin changes may worsen.
• If you notice any suspicious skin changes. Contact your doctor, as there is an increased risk of certain types of skin cancer (non-melanoma skin cancer) during treatment with this medication.
• If you experience a painful, red, or purple rash with blisters and (or) other mucosal changes (e.g., in the mouth and on the lips), especially if you have previously experienced hypersensitivity to light, respiratory infection (e.g., bronchitis), and (or) fever.
• In cases of pre-existing heart disease (e.g., heart attack, chest pain, severe heart rhythm disorders).
• If you experience any pain, blood in the urine, or decreased urine output. In advanced cancer stages, unnecessary products from dying tumor tissue may be removed from the body with delay. This phenomenon is called tumor lysis syndrome and may lead to kidney failure and heart problems within 48 hours of the first dose of Bendamustine Kabi. Your doctor should ensure you are properly hydrated and may administer other medications to prevent this phenomenon.
• In cases of severe allergic reactions or hypersensitivity reactions. The injection site should be monitored after the first treatment cycle.

Bendamustine Kabi and Other Medications

Inform your doctor or pharmacist about all medications you are currently taking or have recently taken, as well as any medications you plan to take.
In cases where bendamustine is used in combination with medications that suppress blood cell production in the bone marrow, the effect on bone marrow function may be enhanced.
Bendamustine used in combination with medications that affect the immune response may enhance this effect.
Cytostatic medications may reduce the effectiveness of vaccinations using live viruses.
Cytostatic medications also increase the risk of infection after vaccination with live vaccines (e.g., live viral vaccines).

Pregnancy, Breastfeeding, and Fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor or pharmacist before using this medication.
Pregnancy
Bendamustine may cause genetic damage and birth defects in animal studies. Bendamustine Kabi should not be used during pregnancy unless your doctor considers it absolutely necessary. If treatment is started, discuss possible side effects on the unborn child and undergo genetic testing.
If you become pregnant during Bendamustine Kabi treatment, inform your doctor immediately and undergo genetic testing.
Pregnancy Precautions for Women and Men
Men
Men should not father a child during Bendamustine Kabi treatment and for 3 months after treatment ends.
Women
Women of childbearing age must use effective contraception during treatment and for 6 months after the last dose of Bendamustine Kabi.
Breastfeeding
Bendamustine Kabi should not be used during breastfeeding. If treatment is necessary, breastfeeding should be stopped.
Fertility
Men
There is a risk that Bendamustine Kabi treatment may cause infertility. Men wishing to have children should consult about sperm preservation before starting treatment.
Women
Women wishing to have children after treatment should consult their doctor.

Driving and Operating Machinery

Bendamustine has a significant impact on the ability to drive and operate machinery.
Do not drive or operate machinery if you experience side effects such as dizziness or coordination problems.

3. How to Use Bendamustine Kabi

This medication should always be used as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Bendamustine Kabi is administered intravenously over 30-60 minutes, in different doses, either as a single medication (monotherapy) or in combination with other medications.
Treatment should not be started if the white blood cell count (leukocytes) and (or) platelet count decreases below the level established by your doctor. Your doctor will monitor these parameters at regular intervals.

Chronic Lymphocytic Leukemia

Non-Hodgkin's Lymphoma

Multiple Myeloma

Treatment should be discontinued if the white blood cell count (leukocytes) and (or) platelet count decreases below the level established by your doctor. Treatment can be continued when the white blood cell and platelet counts increase.
Liver or Kidney Dysfunction
Depending on the degree of liver dysfunction, the dose may need to be adjusted (by 30% in cases of moderate liver dysfunction). No dose adjustment is necessary if the patient has kidney dysfunction. The treating physician will decide whether a dose adjustment is necessary.
Administration Method
Bendamustine Kabi treatment should only be initiated by experienced oncologists. The doctor will administer the appropriate dose of Bendamustine Kabi and take necessary precautions.
The treating physician will administer the solution for infusion after preparation according to the instructions.
The solution is administered intravenously as a short-term infusion over 30-60 minutes.
Treatment Duration
No general time limit for Bendamustine Kabi treatment has been established. The duration of treatment depends on the disease and response to treatment.
In case of doubts or questions about using Bendamustine Kabi, consult your doctor or nurse.
Missing a Dose of Bendamustine Kabi
If a dose of Bendamustine Kabi is missed, the doctor will usually continue treatment according to the established dosing schedule.
Discontinuing Bendamustine Kabi Treatment
The treating physician will decide whether to discontinue treatment or switch to another medication.
In case of doubts about using the medication, consult your doctor or pharmacist.

4. Possible Side Effects

Like all medications, Bendamustine Kabi can cause side effects, although not everyone will experience them.
Some of the following side effects can be detected through tests performed by your doctor.
Very rarely, after Bendamustine Kabi leakage into tissue outside the blood vessel (extravasation), tissue necrosis (necrosis) has been observed. A symptom of medication leakage outside the blood vessel may be a burning sensation at the injection site. This can lead to pain and poor wound healing.
The dose-limiting side effect of Bendamustine Kabi is bone marrow dysfunction, which usually returns to normal after treatment. Bone marrow suppression can lead to a decrease in blood cell count, which can increase the risk of infection, anemia, or bleeding.
Very Common(may occur in more than 1 in 10 patients):

• low white blood cell count (immunocompromised state);
• decreased hemoglobin (protein in red blood cells responsible for oxygen transport);
• low platelet count (cells responsible for blood clotting);
• infections;
• nausea;
• vomiting;
• mucositis;
• increased creatinine levels (metabolic product in muscles) in serum;
• increased urea levels (metabolic product) in serum;
• fever;
• weakness;
• headache.

Common(may occur in up to 1 in 10 patients):

• bleeding (hemorrhage);
• metabolic disorders related to the release of tumor cell contents into the blood;
• decreased red blood cell count, which can cause pale skin and weakness or shortness of breath (anemia);
• decreased neutrophil count (type of white blood cell responsible for fighting infections);
• hypersensitivity reactions, such as allergic skin inflammation, hives;
• increased liver enzyme activity (ASAT/ALAT), which may indicate liver inflammation or damage;
• increased alkaline phosphatase activity (enzyme produced mainly in the liver and bones);
• increased bilirubin levels (substance produced during red blood cell breakdown);
• decreased potassium levels in the blood (necessary for proper nerve and muscle function, including heart muscle);
• heart disorders, such as palpitations, chest pain (angina pectoris);
• heart rhythm disorders (arrhythmia);
• low or high blood pressure;
• lung function disorders;
• diarrhea;
• constipation;
• mouth pain, mouth inflammation;
• loss of appetite;
• hair loss;
• skin changes;
• amenorrhea (absence of menstruation);
• pain;
• insomnia;
• chills;
• dehydration;
• dizziness;
• itching (pruritus).

Uncommon(may occur in up to 1 in 100 patients):

• fluid accumulation in the pericardial sac (pericardial effusion);
• ineffective blood cell production in the bone marrow (bone marrow failure);
• acute leukemia;
• heart attack, chest pain (myocardial infarction);
• heart failure.

Rare(may occur in up to 1 in 1000 patients):

• blood infection (sepsis);
• severe hypersensitivity reactions (anaphylactic reactions);
• bone marrow suppression that can cause poor health or be detected in blood test results;
• symptoms similar to anaphylactic reactions (pseudoanaphylactic reactions);
• drowsiness;
• loss of voice (aphonia);
• acute circulatory collapse (cardiac arrest, mainly of cardiac origin, leading to tissue hypoxia and hypercapnia);
• skin redness (erythema);
• skin inflammation;
• itching;
• skin rash (exanthema);
• excessive sweating.

Very Rare(may occur in up to 1 in 10,000 patients):

• primary atypical pneumonia;
• red blood cell breakdown;
• sudden drop in blood pressure, sometimes with skin reactions or rash (anaphylactic shock);
• taste disorders;
• numbness or tingling (paresthesia);
• poor overall health and limb pain (peripheral neuropathy);
• severe condition resulting from blockage of certain receptors in the nervous system;
• nervous system disorders;
• coordination disorders (ataxia);
• brain inflammation;
• rapid heart rate (tachycardia);
• vein inflammation;
• lung tissue formation (pulmonary fibrosis);
• bleeding esophagitis (bleeding inflammation of the esophagus);
• stomach or intestinal bleeding;
• infertility;
• multi-organ failure.

Frequency Not Known(frequency cannot be estimated from available data):

• liver failure;
• kidney failure;
• irregular or rapid heart rhythm (atrial fibrillation);
• boils, high fever, lymph node enlargement, and symptoms affecting various organs (drug reaction with eosinophilia and systemic symptoms, also known as DRESS syndrome or hypersensitivity syndrome);
• severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. These may appear as red or circular spots on the skin, often with central blisters on the torso, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes, and may be preceded by fever and flu-like symptoms.

There have been reports of the development of tumors (myelodysplastic syndrome, acute myeloid leukemia, lung cancer) in patients using bendamustine. However, the relationship between their occurrence and bendamustine use has not been conclusively established.
Immediately consult your doctor if you experience any of the following side effects (frequency not known):
Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Reporting Side Effects

If you experience any side effects, including those not listed in this package leaflet, inform your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocides
Al. Jerozolimskie 181C
02-222 Warsaw
tel.: +48 22 49 21 301
fax: +48 22 49 21 309
website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help gather more information on the safety of the medication.

5. How to Store Bendamustine Kabi

Store the medication out of sight and reach of children.
Do not use this medication after the expiration date stated on the vial and outer packaging after: EXP. The expiration date refers to the last day of the specified month.
No special storage instructions are provided for the medication.

Shelf Life After Opening and Preparation of the Solution

The solution for infusion prepared according to the instructions at the end of the package leaflet and stored in polyethylene bags remains stable for 3.5 hours at 25°C and 60% relative humidity and for 2 days when refrigerated. Bendamustine Kabi does not contain preservatives, so solutions should not be used after the specified times.
From a microbiological point of view, the medication should be used immediately. If not used immediately, the user is responsible for the storage time and conditions before use. The storage time should not exceed 24 hours at 2°C - 8°C if reconstitution and dilution were performed under controlled, validated aseptic conditions.
Do not use this medication if visible signs of deterioration are observed.
Medications should not be disposed of in wastewater or household waste. Ask your pharmacist how to dispose of unused medications. This will help protect the environment.

6. Package Contents and Other Information

What Bendamustine Kabi Contains

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The active substance of the medication is bendamustine hydrochloride.
One vial contains 25 mg of bendamustine hydrochloride.
One vial contains 100 mg of bendamustine hydrochloride.
After reconstitution, 1 mL of the concentrate contains 2.5 mg of bendamustine hydrochloride.
­ The other ingredient is mannitol.

What Bendamustine Kabi Looks Like and Package Contents

Vials made of orange type I glass with a chlorobutyl rubber stopper and a flip-off aluminum cap (green or blue).
White to off-white lyophilized powder.
Bendamustine Kabi is available in packages of 1, 5, 10, and 20 vials containing 25 mg of bendamustine hydrochloride and 1 and 5 vials containing 100 mg of bendamustine hydrochloride.

Marketing Authorization Holder

Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warsaw

Importer

Fresenius Kabi Deutschland GmbH
Pfingstweide 53
61169 Friedberg
Germany
To obtain more detailed information, contact the marketing authorization holder:
Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warsaw
tel.: +48 22 345 67 89

This Medication is Authorized for Use in European Economic Area Member States Under the Following Names:

Date of Last Revision of the Package Leaflet:23.05.2024
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Information Intended for Healthcare Professionals Only:

As with all cytotoxic substances, due to the potential for genetic damage and cancer, nursing staff and doctors should take more stringent precautions than usual.
When handling Bendamustine Kabi, avoid inhalation (inhalation) and skin or mucous membrane contact (wear gloves, protective clothing, and a face mask if possible).
In case of medication spillage on any part of the body, wash the area thoroughly with soap and water and rinse the eyes with 9 mg/mL (0.9%) isotonic sodium chloride solution.
It is recommended to work on a specially secured bench (under a laminar flow) with a non-permeable, single-use absorbent film.
Contaminated items are cytostatic waste.
Follow national guidelines for disposing of materials with cytostatic properties.
Pregnant women should not prepare cytostatics.
For single use only.

• 1. Preparation of the Concentrate The concentrate should be prepared by dissolving the contents of the Bendamustine Kabi vial in water for injection only, as follows: ­ The contents of one vial of Bendamustine Kabi, containing 25 mg of bendamustine hydrochloride, should be dissolved in 10 mL of water for injection by shaking. ­ The contents of one vial of Bendamustine Kabi, containing 100 mg of bendamustine hydrochloride, should be dissolved in 40 mL of water for injection by shaking.
• 2. Preparation of the Solution for Infusion Immediately after obtaining a clear solution (usually within 5-10 minutes), the recommended dose of Bendamustine Kabi should be diluted in 0.9 mg/mL (0.9%) isotonic sodium chloride solution to a final volume of approximately 500 mL. Bendamustine Kabi should not be diluted with any other injection solution. Bendamustine Kabi should not be mixed with other substances during infusion.
• 3. Administration The solution should be administered as an intravenous infusion over 30-60 minutes. For single use only. Any unused medication or waste should be disposed of according to local regulations. Accidental injection of the medication into tissue outside the blood vessel (extravasation) should be stopped immediately. After brief aspiration of the injected fluid, the needle should be withdrawn. The injection site should be cooled and the arm elevated. It is not established whether the administration of additional medications, such as corticosteroids, may have a positive effect (see section 4).