Leaflet: information for the user

Bendamustine Accord 25 mg/ml concentrate for solution for infusion

Bendamustine, hydrochloride

Read this leaflet carefully before you start using the 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 should not be given to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet.See section 4.

1. What is Bendamustine Accord and what it is used for

2. What you need to know before starting to use Bendamustine Accord

3. How to use Bendamustine Accord

4. Possible side effects

5. Storage of Bendamustine Accord

6. Contents of the pack and additional information

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

This medication 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 Accord

• If you are allergic to bendamustine hydrochloride or any of the other components of this medication (listed in section 6)
• During breastfeeding, if treatment with this medication is necessary during breastfeeding, stop breastfeeding (see Pregnancy, breastfeeding and fertility section)
• If you have severe liver dysfunction (liver cell functional damage)
• If you have a yellowish 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 this medication

• If your bone marrow has reduced ability to replace blood cells. Your doctor should measure the number of white blood cells and platelets in your blood before starting treatment with this medication, before each treatment cycle, and between cycles.
• In case of infections. If you experience signs of infection, such as fever or respiratory symptoms, contact your doctor.
• If you experience skin reactions during treatment with this medication. Skin reactions may increase in intensity.
• In case of rash or red or lilac painful blisters on the mucous membrane (e.g. mouth or lips), particularly if you have previously been sensitive 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 notice blood in your urine or if you urinate less. If your disease is very severe, your body may not be able to eliminate all the waste products of dying cancer cells. This is called tumor lysis syndrome and can cause kidney failure and heart problems within 48 hours of the first dose of this medication. Your doctor will ensure that you are adequately hydrated and will give you other medications to prevent this from happening.
• In case of severe allergic or hypersensitivity reactions, be aware of reactions to infusion after your first treatment cycle.

Inform your doctor immediately if you notice or someone notices in you: memory loss, cognitive difficulties, difficulty walking or loss of vision. These symptoms may be due to a rare but serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML).

Contact your doctor if you notice 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 medication.

Other medications and Bendamustina Accord

Inform your doctor or pharmacist if you are using, have used recently or may need to use any other medication, including over-the-counter medications.

If this medication 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 this medication is used in combination with medications that alter your immune response, this effect may be intensified.

Cytostatics may reduce the effectiveness of live virus vaccines. In addition, cytostatics 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

This medication may cause genetic damage and has caused malformations in studies conducted on animals. It should not be used during pregnancy unless the doctor considers it clearly necessary. If you receive this treatment, ask a doctor to explain the risk of possible adverse effects of the treatment for your child. Genetic counseling is recommended.

Fertility

If you are a woman of childbearing age, you must use effective contraceptive measures before and during treatment with this medication. If you become pregnant during treatment with this medication, inform your doctor immediately and seek genetic counseling.

If you are a man, you should not father children during treatment with this medication and for 6 months after treatment. There is a risk that treatment with bendamustina may cause sterility; you may want to seek advice on sperm preservation before starting treatment.

Men treated with this medication should not father children during treatment or for 6 months after treatment. Before starting treatment, you should seek advice on sperm preservation, as there is a possibility that it may cause permanent sterility.

Breastfeeding

Bendamustina should not be administered during breastfeeding. If you need treatment with this medication during breastfeeding, you should stop breastfeeding.

Consult your doctor or pharmacist before using any medication.

Driving and operating machinery

No studies have been conducted on the effects on the ability to drive and operate machinery. Do not drive or operate machinery if you experience adverse effects such as dizziness or lack of coordination.

Use this medicine exactly as your doctor or pharmacist has told you. Talk to your doctor or pharmacist if you are unsure.

This medicine is administered through a vein over 30 to 60 minutes in various doses, either alone (monotherapy) or combined with other medicines.

You will not be able to start treatment if your white blood cell (leukocyte) 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 your white blood cell (leukocyte) and/or platelet count is below certain levels. Treatment may be resumed when your leukocyte and platelet counts have increased.

Renal or Hepatic Insufficiency

Dose adjustment may be necessary based on the degree of liver function deterioration (up to 30% in case of moderate liver function 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

This medicine can only be administered by experienced oncologists. Your doctor will administer the exact dose of this medicine and take necessary precautions.

Your doctor will administer the prepared solution for infusion. The solution is administered through a vein as a brief infusion over 30 to 60 minutes.

Treatment Duration

The exact duration of treatment with this medicine has not been defined. Treatment duration depends on the disease and response to treatment.

If you are concerned or have any doubts about treatment with this medicine, talk to your doctor or pharmacist.

If You Miss a Dose of Bendamustine Accord

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

If You Interrupt Treatment with Bendamustine Accord

Your doctor will decide if treatment should be interrupted or if a different preparation should be used.

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

Like all medicines, Bendamustine Accord can cause side effects, although not everyone will experience them. Some of the reactions mentioned below may occur after your doctor has performed some blood tests.

In rare cases, tissue alterations (due to cellular damage resulting in premature cell death) have been observed after unintentional injection into the tissue surrounding blood vessels (extravascular). If the product is administered outside a vein, there may be a burning sensation at the injection site. The consequences of this administration may be pain and skin healing problems.

The dose-limiting side effect of this medication is a bone marrow function alteration, which usually normalizes. Bone marrow function suppression may lead to low blood cell levels, which in turn may increase the risk of infection, anemia, or intensify the risk of bleeding.

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

• Reduction in white blood cell count (blood defenses)
• Reduction in red blood cell pigment (hemoglobin: a protein in red blood cells that transports oxygen throughout the body)
• Reduction in platelet count (colorless blood cells that collaborate in blood coagulation)
• Infections
• Nausea
• Vomiting
• Mucous membrane inflammation
• Increased blood creatinine concentration (a waste product produced by muscles)
• Increased blood urea concentration (a waste product)
• Fever
• Fatigue
• Headache

Common (may affect up to 1 in 10 people)

• Bleeding (hemorrhage)
• Metabolic alteration caused by dying cancer cells, which release their contents into the circulatory system
• Decreased red blood cells, which may cause pale skin and cause weakness or difficulty breathing (anemia)
• Abnormally low neutrophil count (a type of white blood cell) in the blood, which may result in increased sensitivity to infections (neutropenia)
• Hypersensitivity reactions, such as skin inflammation (dermatitis) or urticaria
• Elevation of liver enzymes AST/ALT, which may indicate liver inflammation or damage
• Increased alkaline phosphatase enzyme (an enzyme primarily produced in the liver and bones)
• Increased bilirubin pigment (a substance generated during normal red blood cell degradation)
• Low potassium blood level (a nutrient necessary for nerve and muscle cell function, including heart cells)
• Cardiac function alteration (dysfunction)
• Cardiac rhythm alteration (arrhythmia)
• Elevated or decreased blood pressure (hypotension or hypertension)
• Pulmonary function alteration
• Dyspepsia
• Constipation
• Mouth ulcers (stomatitis)
• Loss of appetite
• Hair loss
• Skin alterations
• Amenorrhea (absence of menstruation)
• Pain
• Insomnia
• Chills
• Dehydration
• Dizziness
• Excessive sweating (hyperhidrosis)
• Reduction in bone marrow function, which may cause you to feel unwell or appear in your blood test results

• Accumulation of fluid in the sac surrounding the heart (pericardial effusion)
• Ineffective production of all blood cells (the spongy material inside your 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 people)

• Blood infection (sepsis)
• Severe allergic and hypersensitivity reactions (anaphylactic reactions)
• Reactions similar to anaphylactic reactions (anaphylactoid reactions)
• Somnolence
• Loss of voice (aphonia)
• Acute circulatory failure (failure in blood circulation primarily of cardiac origin with failure to maintain oxygen and nutrient supply to tissues and toxin removal)
• Skin redness (erythema)
• Skin inflammation (dermatitis)
• Itching (pruritus)
• Maculopapular exanthema (skin rash)
• Excessive sweating (hyperhidrosis)
• Reduction in bone marrow function, which may cause you to feel unwell or appear in your blood test results

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

• Atypical primary lung inflammation (pneumonia)
• Red blood cell destruction
• Rapid decrease in blood pressure, sometimes with skin reactions (anaphylactic shock)
• Alteration of taste
• Alteration of sensitivity (paresthesias)
• Discomfort and pain in the extremities (peripheral neuropathy)
• Anticholinergic syndrome (inhibition of the physiological action of acetylcholine, especially as a neurotransmitter)
• Neurological disorders (diseases of the brain, spinal cord, and nerves that connect them)
• Ataxia (lack of coordination)
• Encephalitis (inflammation of the brain)
• Increased heart rate (tachycardia)
• Vein inflammation (phlebitis)
• Pulmonary fibrosis (formation of tissue in the lungs)
• Esophageal inflammation with hemorrhage (esophagitis hemorrhagica)
• Gastric or intestinal hemorrhage
• Infertility
• Multi-organ failure

Frequency not known (cannot be estimated from available data)

• Renal failure
• Liver failure
• Irregular and usually rapid heart rhythm (atrial fibrillation)
• Red rash or purple blisters and painful on mucous membranes (e.g., mouth or lips), particularly if you have previously had sensitivity to light, respiratory system infections (e.g., bronchitis), or fever.
• Drug rash in combination with rituximab treatment
• Pneumonitis
• Bleeding from the lungs

There have been reports of tumors (myelodysplastic syndromes, LMA, bronchial carcinoma) after treatment with bendamustine. A clear relationship with bendamustine could not be determined.

Contact your doctor or seek immediate medical attention if you experience any of the following side effects (frequency not known):

Severe skin eruptions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. These may appear as circular, red spots with central blisters on the trunk, peeling, mouth ulcers, throat, nose, genitals, and eyes, which may be preceded by fever and flu-like symptoms.

Widespread rash, high body temperature, swollen lymph nodes, and other organ changes (Drug Reaction with Eosinophilia and Systemic Symptoms, also known as DRESS or drug hypersensitivity syndrome).

If any side effect worsens, or if you notice any side effect not included 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 it is a side effect not listed in this prospectus. You can also report them directly through theSistema Español de Farmacovigilancia de Medicamentos de Uso Humano:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

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

Store and transport refrigerated (2-8°C). Do not freeze.

Do not use this medication if you detect visible particles in the solution or if the solution is not transparent or yellowish.

After opening the vial

Chemical, physical, and microbiological stability has been demonstrated for 28 days at 2-8°C.

Once opened, the product must be stored for a maximum of 28 days at 2-8°C.

Infusion solution

After dilution, physical and chemical stability has been demonstrated for 3.5 hours at 25°C and 2 days at 2-8°C in polyethylene bags.

From a microbiological standpoint, the solution should be used immediately. If not used immediately, the storage conditions and times before use are the responsibility of the user.

The minimization of the risk of contamination of the multidose vial during the withdrawal of each dose is the responsibility of the user. Record the date and time of the first dose withdrawn on the vial label. Between uses, do not equilibrate the product solution with water for injectable preparations or any diluent and return the multidose vial to the recommended storage condition of 2-8°C.

Medications should not be disposed of through the drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you do not need. This will help protect the environment.

Composition of Bendamustine Accord

The active ingredient ishydrochloride ofbendamustine.

Each ml of concentrate for solution for infusion contains 25 mg ofhydrochlorideof bendamustine (as monohydrate).

Each vial of 1 ml contains 25 mg ofhydrochlorideof bendamustine (as monohydrate).

Each vial of 4 ml contains 100 mg ofhydrochlorideof bendamustine (as monohydrate).

The other components are butylhydroxytoluene (E321) and macrogol.

Appearance of the product and contents of the container

Clear, colourless to yellowish solution in a topaz glass vial with a chlorobutyl rubber stopper containing 1 ml and 4 ml of concentrate for solution for infusion. The 1 ml vial is provided with an aluminium cap with a red removable plastic cap, and the 4 ml vial is provided with an aluminium cap of red colour with a white removable plastic cap.

Bendamustine Accord is marketed in packs containing 1 or 5 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Accord Healthcare, S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6th floor

08039 Barcelona

Spain

Responsible Person

Accord Healthcare, S.p.z.o.o

Ul Lutomierska, 50

95-200 Pabianice

Poland

This medicinal product is authorised in the Member States of the European Economic Area under the following names:

Last update of the summary of product characteristics:November 2023

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

This information is intended solely for medical professionals or healthcare professionals:

As with all similar cytotoxics, nursing staff and doctors must exercise extreme caution, due to the potential genotoxicity and carcinogenicity of the preparation. Avoid inhalation (inspiration) and contact with the skin and mucous membranes while handling Bendamustine Accord (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 isotonic saline solution (0.9%). If possible, it is recommended to work on a special safety workbench (laminar flow) with a disposable, impermeable to liquids, absorbent sheet. Contaminated items are cytotoxic waste. Please follow national guidelines for the disposal of cytotoxic material. Pregnant nursing staff should not work with cytotoxics.

The concentrate for solution for infusion must be diluted with a sodium chloride 9mg/ml (0.9%) injection solution and then administered by intravenous infusion. An aseptic technique will be used.

1. Dilution

Aspirate aseptically the required volume for the required dose from the 25 mg/ml vial of Bendamustine Accord. Dilute the total recommended dose of Bendamustine Accord 25 mg/ml with a 0.9% sodium chloride solution to produce a final volume of approximately 500 ml.

When diluting the product, it should be noted that the concentration (25 mg/ml) of bendamustine in Bendamustine Accord is higher than in the usual bendamustine concentrates resulting from the reconstitution of bendamustine-containing medicinal products in powder form.

Bendamustine Accord 25 mg/ml must be diluted with a 0.9% sodium chloride solution and not with any other injection solution.

Dilution, as recommended, results in a clear, colourless to yellowish solution, practically free of visible particles.

2. Administration

The solution is administered by intravenous infusion over 30 to 60 minutes.

The vials are for multiple use.

The product must be inspected before use. When inspected, visible particles in the solution or discoloration of the solution are signs of deterioration. The product should not be used if deteriorated.

Any unused medicinal product or waste must be disposed of in accordance with local requirements.

Unintentional injection into tissue outside the blood vessels (extravasation) must be stopped immediately. The needle must be withdrawn after a brief aspiration. The affected tissue area must then be cooled. The arm must be elevated. Additional treatments such as the use of corticosteroids do not offer clear benefits.