Bendamustine Accord

Package Leaflet: Information for the User

Bendamustine Accord, 25 mg/ml, Concentrate for Solution for Infusion

Bendamustine Hydrochloride

Read All of This Leaflet Carefully Before You Start Taking This Medicine.

• You should keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Pack

• 1. What is Bendamustine Accord and What is it Used For
• 2. Before You Take Bendamustine Accord
• 3. How to Take Bendamustine Accord
• 4. Possible Side Effects
• 5. How to Store Bendamustine Accord
• 6. Contents of the Pack and Other Information

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

Bendamustine Accord is a medicine used to treat certain types of cancer (cytotoxic medicine).
Bendamustine Accord is used alone (as monotherapy) or in combination with other medicines to treat the following types of cancer:

• Chronic lymphocytic leukemia when fludarabine-containing chemotherapy is not appropriate,
• Non-Hodgkin's lymphoma that has not responded or has responded inadequately to prior rituximab treatment,
• Multiple myeloma when treatment with a thalidomide- or bortezomib-containing chemotherapy regimen is not appropriate.

2. Before You Take Bendamustine Accord

When Not to Take Bendamustine Accord

• 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 Accord is necessary, you must stop breastfeeding (see "Warnings and Precautions" and "Pregnancy, Breastfeeding, and Fertility"),
• If you have severe liver damage (liver cell function impairment),
• If you have jaundice or yellowing of the skin and eyes due to liver or blood disorders (jaundice),
• If you have severe bone marrow disorders (bone marrow depression) and significant changes in white blood cell and platelet counts;
• If you have undergone major surgery within 30 days before starting treatment,
• If you have an infection, especially with a low white blood cell count (leukopenia),
• If you have been vaccinated against yellow fever.

Warnings and Precautions

Before starting treatment with Bendamustine Accord, discuss with your doctor, pharmacist, or nurse:

• if you have reduced bone marrow function. Your doctor will check your white blood cell and platelet counts before starting treatment with Bendamustine Accord, before each subsequent treatment cycle, and during treatment breaks.
• if you have infections. Contact your doctor if you experience symptoms of infection, including fever and respiratory symptoms.
• if you experience skin changes during treatment with Bendamustine Accord. These changes can worsen.
• if you experience a painful, red, or purple rash with blisters and/or other skin or mucous membrane changes (e.g., in the mouth and on the lips), especially if you have previously experienced sensitivity to light, respiratory infections (e.g., bronchitis), and/or fever.
• if you have pre-existing heart disease (e.g., heart attack, chest pain, severe arrhythmias).
• if you experience pain, blood in your urine, or decreased urine output. In advanced cancer, dying tumor tissue may be removed from the body slowly. This phenomenon is called tumor lysis syndrome and can lead to kidney failure and heart problems within 48 hours of the first dose of Bendamustine Accord. Your doctor should ensure that you are properly hydrated and can administer other medications to prevent this phenomenon.
• if you experience severe allergic reactions or hypersensitivity reactions. Monitor the injection site after the first treatment cycle.

Tell your doctor immediately if you experience any of the following symptoms during or after treatment: memory loss, thinking problems, difficulty walking, or vision loss - these may be signs of a rare but serious brain infection (progressive multifocal leukoencephalopathy, PML), which can be fatal.
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 medicine.

Bendamustine Accord and Other Medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take.
When using Bendamustine Accord in combination with other medicines that suppress bone marrow function, the effect on bone marrow function may be enhanced.
Bendamustine Accord used in combination with medicines that affect the immune response may increase this effect.
Cytostatic medicines may reduce the effectiveness of live virus vaccines. Cytostatic medicines also increase the risk of infection after live vaccinations (e.g., antiviral vaccines).

Pregnancy, Breastfeeding, and Fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

Bendamustine Accord may cause genetic damage and birth defects in animals. Do not take Bendamustine Accord during pregnancy unless your doctor considers it absolutely necessary. If treatment is necessary, discuss possible side effects with your doctor and undergo genetic testing if recommended.
Women of childbearing age must use effective contraception before, during, and for at least 6 months after treatment with Bendamustine Accord. Do not become pregnant during treatment with Bendamustine Accord and for at least 6 months after the last dose. If you become pregnant during treatment with Bendamustine Accord, inform your doctor immediately and undergo genetic testing.

Breastfeeding

Do not take Bendamustine Accord during breastfeeding. If treatment with Bendamustine Accord is necessary, stop breastfeeding.
Consult your doctor before taking any medicine.

Contraception in Men and Women

Women should not become pregnant during treatment and for at least 6 months after the last dose. Men should take appropriate precautions to avoid causing their partner to become pregnant during treatment with Bendamustine Accord and for at least 3 months after the last dose.

Fertility

Men taking Bendamustine Accord should not plan to conceive a child during treatment and for 3 months after the last dose. Before starting treatment, consult about the possibility of storing sperm due to the risk of permanent infertility.

Driving and Using Machines

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

3. How to Take Bendamustine Accord

Take this medicine exactly as your doctor or pharmacist has told you.
If you are not sure, ask your doctor or pharmacist.
Bendamustine Accord is given by infusion into a vein over 30-60 minutes, in different doses, either alone or in combination with other medicines.
Do not start treatment if your white blood cell and/or platelet count is below the level determined by your doctor.
Your doctor will check these parameters at regular intervals.

Chronic Lymphocytic Leukemia

Non-Hodgkin's Lymphoma

Multiple Myeloma

Treatment should be discontinued if your white blood cell and/or platelet count drops below the level determined by your doctor. Treatment can be continued when your white blood cell and platelet counts increase.
Liver or kidney function disorders
Depending on the degree of liver function disorders, dose adjustment may be necessary (by 30% in case of moderate liver function disorders). No dose adjustment is necessary if you have kidney failure. Your doctor will decide whether dose adjustment is necessary.
Administration
Bendamustine Accord therapy should only be initiated by doctors experienced in the treatment of cancer.
Your doctor will administer the appropriate dose of Bendamustine Accord and take necessary precautions.
Your doctor will administer the infusion solution prepared according to the recommendations.
Duration of Treatment
No overall time limit for treatment with Bendamustine Accord has been established.
The duration of treatment depends on the disease and how you respond to treatment.
If you have any doubts or questions about treatment with Bendamustine Accord, consult your doctor or nurse.

Missing a Dose of Bendamustine Accord

If you miss a dose of Bendamustine Accord, your doctor will usually continue treatment according to the prescribed dosing schedule.

Stopping Treatment with Bendamustine Accord

Your doctor will decide whether to stop treatment or change the medicine.
If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible Side Effects

Like all medicines, Bendamustine Accord can cause side effects, although not everybody gets them.
Some of the side effects listed below may only be recognized after blood tests or medical evaluations by your doctor.
Very rarely, after accidental injection of Bendamustine Accord outside the blood vessel (extravasation), tissue changes (necrosis) have been observed.
A symptom of extravasation may be a burning sensation at the injection site. Consequences of extravasation can include pain and poorly healing skin damage.
The dose-limiting side effect of Bendamustine Accord is bone marrow suppression, which usually returns to normal after treatment. Bone marrow suppression can lead to a decrease in blood cell counts, increasing the risk of infection, bleeding, or anemia.

Very Common (May Affect More Than 1 in 10 People):

• Decreased white blood cell count (leukopenia)
• Decreased hemoglobin (red blood cell protein responsible for transporting oxygen to cells)
• Decreased platelet count (thrombocytopenia)
• Infections
• Nausea (nausea)
• Vomiting
• Mucositis (inflammation of the mucous membranes)
• Increased creatinine levels in the blood (product of muscle metabolism)
• Increased urea levels in the blood (product of metabolism in the body)
• Fever
• Weakness
• Headache

Common (May Affect Up to 1 in 10 People):

• Bleeding (hemorrhage)
• Metabolic disorders related to the release of tumor cell contents into the bloodstream
• Anemia (low red blood cell count, which can cause pale skin and weakness or shortness of breath)
• Low neutrophil count (type of white blood cell important for fighting infections)
• Hypersensitivity reactions, such as allergic skin inflammation, hives
• Increased liver enzyme activity (ASAT/ALAT, which may indicate liver inflammation or cell damage)
• Increased alkaline phosphatase activity (enzyme produced mainly in the liver and bones)
• Increased bilirubin levels in the blood (bile pigment produced during the breakdown of red blood cells)
• Decreased potassium levels in the blood (necessary for proper nerve and muscle function, including heart muscle)
• Heart function disorders
• Arrhythmias (irregular heart rhythm)
• Low or high blood pressure (hypotension or hypertension)
• Lung function disorders
• Diarrhea
• Constipation
• Herpes simplex mouth inflammation
• Loss of appetite
• Hair loss
• Skin changes
• Amenorrhea (absence of menstruation)
• Pain
• Insomnia
• Tremors
• Dehydration
• Dizziness
• Itchy rash (hives)

Uncommon (May Affect Up to 1 in 100 People):

• Fluid accumulation in the pericardial sac (pericardial effusion)
• Ineffective production of all types of blood cells in the bone marrow (bone marrow failure)
• Acute leukemia
• Heart attack, chest pain
• Heart failure

Rare (May Affect Up to 1 in 1000 People):

• Blood infection (sepsis)
• Severe hypersensitivity reactions (anaphylactic reactions)
• Symptoms similar to anaphylactic reactions (anaphylactoid reactions)
• Drowsiness
• Voice loss (aphonia)
• Acute circulatory collapse (cardiac arrest, mainly of cardiac origin, leading to hypoxia and malnutrition of cells and inability to eliminate toxins)
• Redness of the skin (erythema)
• Skin inflammation
• Itching (pruritus)
• Rash (exanthema)
• Excessive sweating
• Bone marrow suppression, which can worsen your condition or be visible in blood test results

Very Rare (May Affect Up to 1 in 10,000 People):

• Primary atypical pneumonia
• Red blood cell destruction
• Sudden drop in blood pressure, sometimes with skin reactions (anaphylactic shock)
• Taste disorders
• Numbness or tingling (paresthesia)
• Poor general condition and limb pain (peripheral neuropathy)
• Severe condition causing blockage of a specific receptor in the nervous system
• Nervous system disorders
• Lack of coordination (ataxia)
• Brain inflammation
• Fast heart rate (tachycardia)
• Vein inflammation
• Scarring in the lungs (pulmonary fibrosis)
• Bleeding esophagitis
• Bleeding from the stomach or esophagus
• Infertility
• Multi-organ failure

Frequency Not Known (Cannot be Estimated from Available Data):

• Kidney failure
• Liver failure
• Irregular or rapid heartbeat (atrial fibrillation)
• Painful red or purple spreading rash with blisters and/or other skin or mucous membrane changes (e.g., in the mouth and on the lips), especially if you have previously experienced sensitivity to light, respiratory infections (e.g., bronchitis), and/or fever.
• Drug rash in combination therapy with rituximab
• Pneumonia
• Bleeding from the lungs
• Excessive urination, also at night, and excessive thirst even after drinking fluids (nephrogenic diabetes insipidus)

There have been reports of the development of tumors (myelodysplastic syndrome, acute myeloid leukemia, lung cancer) in patients taking Bendamustine Accord. However, the relationship between their occurrence and the use of Bendamustine Accord has not been definitively established.
If you experience any of the following side effects (frequency not known), contact your doctor immediately: Severe skin rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis. These can appear as red or circular spots on the skin, often with central blisters on the torso, peeling skin, ulcers in the mouth, throat, nose, genitals, and eyes, and may be preceded by fever and flu-like symptoms.
Widespread rash, high body temperature, swollen lymph nodes, and symptoms affecting various organs (drug rash with eosinophilia and systemic symptoms, also known as DRESS or hypersensitivity syndrome).
If any of your side effects worsen or if you experience any side effects not listed in this leaflet, tell your doctor.

Reporting Side Effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the Department of Drug Safety, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products,
Jerozolimskie Avenue 181C,
02-222 Warsaw,
tel: +48 22 49 21 301,
fax: +48 22 49 21 309,
website: https://smz.ezdrowie.gov.pl
You can also report side effects to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to Store Bendamustine Accord

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after EXP.
The expiry date refers to the last day of the month.
Store and transport at 2-8°C. Do not freeze.
Do not use this medicine if you notice particles or if the solution is not clear and colorless to yellow.
After Opening the Vial
Chemical, physical, and microbiological stability has been demonstrated for 28 days at 2-8°C.
After opening, the product can be stored for a maximum of 28 days at 2-8°C.
Infusion Solution
After dilution, chemical and physical stability has been demonstrated for 3.5 hours at 25°C and 2 days at 2-8°C in polyethylene bags.
From a microbiological point of view, the solution should be used immediately. If not used immediately, the user is responsible for the storage conditions and storage time.
The user is responsible for minimizing the risk of contamination of the multidose vial during each dose withdrawal. Record the date and time of the first dose withdrawal on the vial label.
Between uses, do not refill the solution with water for injections or any diluent, and store the multidose vial in the recommended storage conditions at 2-8°C.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the Pack and Other Information

What Bendamustine Accord Contains

The active substance is bendamustine hydrochloride.
Each milliliter of the concentrate for solution for infusion contains 25 mg of bendamustine hydrochloride (as bendamustine hydrochloride monohydrate).
Each 4 ml vial contains 100 mg of bendamustine hydrochloride (as bendamustine hydrochloride monohydrate).
Each 1 ml vial contains 25 mg of bendamustine hydrochloride (as bendamustine hydrochloride monohydrate).
The other ingredients are butylhydroxytoluene and macrogol 300.

What Bendamustine Accord Looks Like and Contents of the Pack

Clear, colorless to yellow solution in a brown glass vial, closed with a rubber stopper and sealed with an aluminum cap with a red or white plastic flip-off cap.
The vial is protected with a sleeve.
Bendamustine Accord is available in packs containing 1 or 5 vials.
Not all pack sizes may be marketed.

Marketing Authorization Holder

Accord Healthcare Polska Sp. z o.o.
Taśmowa 7 Street
02-677 Warsaw
tel: +48 22 577 28 00

Manufacturer

Accord Healthcare Polska Sp. z o.o.
Lutomierska 50 Street
95-200 Pabianice

This Medicinal Product is Authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) Under the Following Names:

Date of Last Revision of the Leaflet: June 2024

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Information Intended for Healthcare Professionals Only:
As with all similar cytotoxic substances, due to the potential for genetic damage and the development of cancer, nursing staff and doctors should take more stringent precautions than usual. When handling Bendamustine Accord, avoid inhalation (inhalation) of the medicine and its contact with the skin and mucous membranes (wear gloves, protective clothing, and, if possible, a face mask!). In case of contamination of any part of the body with the product, wash it thoroughly with soap and water and rinse the eyes with 0.9% (isotonic) sodium chloride solution. It is recommended to work on special, protected workstations (under a laminar flow) with a covered work surface with a single-use, fluid-impermeable absorbent sheet. Contaminated items are cytostatic waste. Please follow national guidelines for the disposal of cytostatic materials. Pregnant women should not be allowed to work with cytostatic products.
The concentrate for solution for infusion should be diluted with 9 mg/ml (0.9%) sodium chloride solution for injection, and then administered by intravenous infusion. Aseptic technique should be used.

• 1. Dilution Using aseptic technique, withdraw the required volume of Bendamustine Accord from the vial. The total recommended dose of Bendamustine Accord should be diluted in 0.9% sodium chloride solution to a final volume of approximately 500 ml.

During Dilution, Note that the Concentration (25 mg/ml) of Bendamustine in Bendamustine Accord is Higher than in Conventional Bendamustine Formulations Obtained by Reconstituting Powder for Solution for Infusion.

Bendamustine Accord 25 mg/ml should be diluted with 0.9% sodium chloride solution, not with any other injection solution.
Dilution performed according to the recommendations gives a clear, colorless to yellow solution, practically free from visible particles.

• 2. Administration The solution should be administered by intravenous infusion over 30-60 minutes.

The vials are for multiple use.

Check the product before use. If you notice particles or a change in color, it is a sign of spoilage. Do not use the product if it shows signs of spoilage.
Any unused product or waste material should be disposed of in accordance with local regulations.
Accidental injection of Bendamustine Accord 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. The patient's arm should be elevated. It has not been established whether the administration of additional medications such as corticosteroids may have a positive effect.