Bendamustine Accord

Package Leaflet: Information for the User

Bendamustine Accord, 2.5 mg/ml, powder for concentrate for solution for infusion

Bendamustine hydrochloride
The name of the medicine is "Bendamustine Accord 2.5 mg/ml, powder for concentrate for solution for infusion", but in the rest of the leaflet, the shorter name "Bendamustine Accord" is used.

Read all of this leaflet carefully before you start taking this medicine.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• 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, pharmacist, or nurse. 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 (monotherapy) or in combination with other medicines to treat the following types of cancer:

• Chronic lymphocytic leukemia when fludarabine-containing chemotherapy is not recommended,
• 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 recommended.

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 during this period, you must stop breastfeeding your baby (see "Warnings and precautions" and "Pregnancy, breastfeeding, and fertility");
• If you have severe liver damage (liver cell function impairment);
• If you have jaundice (yellowing of the skin or whites of the eyes) due to liver function disorders or blood disorders;
• 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 decrease in 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 cycle of treatment, and during breaks between treatments.
• if you have an infection. 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 may worsen.
• if you experience a painful, red, or purple rash with blisters and/or other changes in the mucous membranes (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 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 Accord. Your doctor should ensure that you are properly hydrated and may administer other medicines to prevent this phenomenon.
• if you experience severe allergic reactions or hypersensitivity reactions. The injection site should be monitored after the first treatment cycle.
• you should immediately tell your doctor if you experience any of the following symptoms at any time during or after treatment: memory loss, thinking problems, difficulty walking, or vision loss - these may be caused by a very rare but serious brain infection (progressive multifocal leukoencephalopathy, PML), which can be fatal.
• if you notice any suspicious skin changes, you should 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 enhance this effect.
Cytotoxic medicines may reduce the effectiveness of live virus vaccines. Cytotoxic 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. Do not become pregnant during treatment with Bendamustine Accord and for at least 6 months after the last dose. If treatment is necessary, discuss with your doctor the possible harmful effects on the unborn child and undergo genetic testing if recommended.
Women of childbearing potential should use effective contraception both before and during treatment with Bendamustine Accord. If you become pregnant during treatment with Bendamustine Accord, tell your doctor immediately and undergo genetic testing.

Breastfeeding

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

Contraception in women and men

Women should not become pregnant during treatment with Bendamustine Accord and for at least 6 months after the last dose.
Men should take appropriate precautions to avoid their partner becoming 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 father a child during treatment and for 3 months after the last dose. Before starting treatment, consult your doctor about the possibility of storing sperm due to the risk of permanent infertility.

Driving and using machines

Bendamustine Accord has a major influence on the ability to drive and use machines.
Do not drive or operate machinery if you experience side effects such as dizziness or coordination problems.

3. How to take Bendamustine Accord

Always 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 (monotherapy) or in combination with other medicines.

Chronic lymphocytic leukemia

Non-Hodgkin's lymphoma

Multiple myeloma

Treatment should be discontinued if the white blood cell count (leukocytes) and/or platelet count decrease below the level determined by your doctor. Treatment can be continued when the white blood cell and platelet counts increase.
Liver or kidney function disorders
Depending on the degree of liver function disorders, it may be necessary to adjust the dose (by 30% in the case of moderate liver function disorders).
No dose adjustment is necessary if you have kidney failure.
Your doctor will decide whether a dose adjustment is necessary.
Administration method
Treatment with Bendamustine Accord should only be initiated by doctors experienced in the treatment of cancer. Your doctor will give you the appropriate dose of Bendamustine Accord and take the necessary precautions.
Your doctor will administer the infusion solution after preparing it according to the instructions.

Missed 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 to another one.
If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine 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 examinations by your doctor.
Very rarely, after accidental injection of Bendamustine Accord into tissue outside a blood vessel (extravasation), tissue changes (necrosis) have been observed.
A symptom of extravasation may be a burning sensation at the injection site. A consequence of extravasation may be pain and poor wound healing.
The side effect of Bendamustine Accord that limits the dose is bone marrow disorders, which usually return to normal after treatment. Bone marrow suppression can lead to a decrease in blood cell count, which can increase the risk of infection, bleeding, or anemia.

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

• Decreased white blood cell count (leukocytes)
• Decreased hemoglobin (red blood cell protein responsible for transporting oxygen to cells)
• Decreased platelet count (blood cells responsible for blood clotting)
• Infections
• Nausea (nausea)
• Vomiting
• Mucositis (inflammation of the mucous membranes)
• Increased creatinine levels in the blood (waste product in muscles)
• Increased urea levels in the blood (waste product 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
• Decreased red blood cell count, which can cause pale skin and weakness or shortness of breath (anemia, anemia)
• 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 cell inflammation or damage)
• Increased alkaline phosphatase activity (enzyme produced mainly in the liver and bones)
• Increased bilirubin levels (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
• Lack 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)
• Failure of blood cell production in the bone marrow (bone marrow failure)
• Acute leukemia
• Heart attack, chest pain
• Heart failure

Rare (may affect up to 1 in 1,000 people):

• Blood infection (sepsis)
• Severe allergic reactions (anaphylactic reactions)
• Symptoms similar to anaphylactic reactions (anaphylactoid reactions)
• Drowsiness
• Voice loss (aphonia)
• Acute circulatory failure (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 cause poor general health or be visible in blood test results

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

• Primary atypical pneumonia
• Red blood cell breakdown
• Sudden drop in blood pressure, sometimes with skin reactions (anaphylactic shock)
• Taste disorders
• Numbness or tingling (paresthesia)
• Poor general health 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, arrhythmia)
• Vein inflammation
• Tissue growth in the lungs (pulmonary fibrosis)
• Bleeding esophagitis
• Bleeding from the stomach or esophagus
• Infertility
• Multi-organ failure

Frequency not known (cannot be estimated from the available data):

• Kidney failure
• Liver failure
• Irregular or rapid heartbeat (atrial fibrillation)
• Painful red or purple spreading rash with blisters and/or other changes in the mucous membranes (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
• Lung inflammation
• Bleeding from the lungs
• Excessive urination, including 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 established.
If you experience any of the following side effects, tell your doctor immediately (frequency not known): Severe skin rashes, 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, peeling of the skin, ulcers in the mouth, throat, nose, genitals, and eyes, and may be preceded by fever and flu-like symptoms.

Reporting side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
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.
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.
There are no special storage instructions for the medicinal product.
Store the vial in its original packaging to protect it from light.

Special precautions for storage after opening the packaging or preparing the infusion solution

The infusion solution prepared according to the instructions is stable in polyethylene bags for 3.5 hours at 25°C and for 2 days at 2-8°C. Bendamustine Accord does not contain preservatives.
From a microbiological point of view, the solution should be used immediately. If the product is not used immediately, the user is responsible for the storage conditions and storage time.
The user is responsible for maintaining aseptic conditions.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Bendamustine Accord contains

The active substance is bendamustine hydrochloride.
1 vial contains 25 mg of bendamustine hydrochloride (as bendamustine hydrochloride monohydrate).
1 vial contains 100 mg of bendamustine hydrochloride (as bendamustine hydrochloride monohydrate).
After reconstitution, 1 ml of concentrate contains 2.5 mg of bendamustine hydrochloride (as bendamustine hydrochloride monohydrate).
The other ingredients are: mannitol.

What Bendamustine Accord looks like and contents of the pack

Vial made of orange type I glass, closed with a bromobutyl rubber stopper, with an aluminum flip-off seal.
Bendamustine Accord is available in packs containing 5, 10, or 20 vials of 25 mg bendamustine hydrochloride and 1 or 5 vials of 100 mg bendamustine hydrochloride.
Not all pack sizes may be marketed.

Marketing authorization holder

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

Manufacturer/Importer

Accord Healthcare Polska Sp. z o.o.
ul. Lutomierska 50
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 cancer, nursing staff and doctors are required to take more stringent precautions than usual. When handling Bendamustine Accord, avoid inhaling the medicine and contact with the skin and mucous membranes (wear gloves, protective clothing, and, if possible, a face mask!). In case of contamination with the product, wash the affected area 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 hood) 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 materials with cytostatic properties. Pregnant women should not be allowed to work with cytostatic products.
The infusion solution should be prepared by dissolving the contents of the Bendamustine Accord vial in water for injections only, as follows:

• 1. Preparation of the concentrate
• Dissolve one vial of Bendamustine Accord containing 25 mg of bendamustine hydrochloride in 10 ml of water for injections by shaking
• Dissolve one vial of Bendamustine Accord containing 100 mg of bendamustine hydrochloride in 40 ml of water for injections by shaking
• 2. Preparation of the infusion solution
  As soon as a clear solution is obtained (usually after 5-10 minutes), the entire dose of Bendamustine Accord should be dissolved immediately in 0.9% (isotonic) sodium chloride solution to obtain a final volume of approximately 500 ml. Bendamustine Accord should not be dissolved in other infusion or injection solutions. Bendamustine Accord should not be mixed with other substances in the infusion.
• 3. Administration
  The solution should be administered as an intravenous infusion over 30-60 minutes. The vials are for single use. Any unused medicinal product or waste materials should be disposed of in accordance with local regulations.

In case of accidental injection of Bendamustine Accord into tissue outside a blood vessel (extravasation), the injection should be stopped immediately. After brief aspiration of the injected fluid, the needle should be withdrawn. The doctor should cool the extravasation site and ask you to elevate your arm. It has not been established whether the administration of additional medicines such as corticosteroids may have a positive effect (see section 4).