Bendamustine Accord 25 mg/ml concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Bendamustina Accord 25 mg/ml concentrate for solution for infusion

Bendamustine, hydrochloride

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only and must not be given to others, even if they have the same symptoms as you. It could harm them.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

1. What Bendamustina Accord is and what it is used for
2. What you need to know before using Bendamustina Accord
3. How to use Bendamustina Accord
4. Possible side effects
5. How to store Bendamustina Accord
6. Contents of the pack and other information

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

Bendamustina Accord is a medicine used to treat certain types of cancer (it is a cytotoxic medicine).

This medicine is used alone (monotherapy) or in combination with other medicines to treat the following types of cancer:

• Chronic lymphocytic leukemia, if combination chemotherapy with fludarabine is not suitable for you.
• Non-Hodgkin's lymphomas that have not responded, or have responded only for a short period of time, following previous treatment with rituximab.
• Multiple myeloma, if treatments containing thalidomide or bortezomib are not suitable for you.

2. What you need to know before using Bendamustina Accord

Do not use Bendamustina Accord

• if you are allergic to bendamustine hydrochloride or to any of the other ingredients of this medicine (listed in section 6)
• during breastfeeding, if treatment with this medicine is necessary during breastfeeding you must stop breastfeeding (see section Pregnancy, breastfeeding and fertility)
• if you have severe liver dysfunction (damage to the functional liver cells)
• if you have yellowing of the skin or whites of the eyes caused by liver or blood problems (jaundice)
• if you have severe bone marrow dysfunction (bone marrow suppression) and severe abnormalities in the number of white blood cells and platelets in the blood
• if you have undergone major surgery within the previous 30 days before starting treatment
• if you have had any infection, especially if accompanied by a reduction in the number of white blood cells (leucopenia)
• in combination with yellow fever vaccines

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use this medicine

• if your bone marrow's ability to replace blood cells is reduced. The number of white blood cells and platelets in the blood should be measured before starting treatment with this medicine, before each treatment cycle, and at intervals between cycles.
• if you have infections. If you experience signs of infection, such as fever or respiratory symptoms, you should contact your doctor.
• if you develop skin reactions during treatment with this medicine. Skin reactions may increase in intensity.
• if red or purplish painful rashes or blisters appear on mucous membranes (e.g., mouth or lips), particularly if you have previously had light sensitivity, respiratory tract infections (e.g., bronchitis), and/or fever.
• if you have a heart condition (e.g., heart attack, chest pain, serious heart rhythm disorders).
• if you experience pain in one side or notice blood in your urine or reduced urination. If your condition is very severe, your body may be unable to eliminate all waste products from dying cancer cells. This is known as tumor lysis syndrome and may lead to kidney failure and heart problems within 48 hours after administration of the first dose of this medicine. Your doctor will ensure you are adequately hydrated and will give you other medications to prevent this from occurring.
• in case of severe allergic or hypersensitivity reactions, you should be alert for infusion reactions after your first treatment cycle.

At any time during or after treatment, inform your doctor immediately if you or someone else notices: 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 the skin, as there may be an increased risk of certain types of skin cancer (non-melanoma skin cancer) with the use of this medicine.

Other medicines and Bendamustina Accord

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including those obtained without a prescription.

If this medicine is used in combination with medicines that suppress bone marrow blood cell formation, the effect on the bone marrow may be intensified.

If this medicine is used in combination with medicines that affect your immune response, this effect may be intensified.

Cytostatic agents may reduce the effectiveness of live virus vaccines. In addition, cytostatic agents increase the risk of infection following vaccination with live virus vaccines (e.g., viral vaccination).

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy

This medicine may cause genetic damage and has caused birth defects in animal studies. It should not be used during pregnancy unless clearly necessary as determined by your doctor. If you receive this treatment, you should ask your doctor to explain the risk of possible adverse effects of the treatment on your unborn child. Genetic counseling is recommended.

If you are a woman of childbearing age, you must use effective contraceptive measures before and during treatment with this medicine. You must not become pregnant during treatment with this medicine and for at least 6 months after the last dose. If you become pregnant during treatment with this medicine, you must inform your doctor immediately and seek genetic counseling.

Breastfeeding

Bendamustine must not be administered during breastfeeding. If treatment with this medicine is required during breastfeeding, you must discontinue breastfeeding.

Consult your doctor or pharmacist before using any medicine.

Contraception in men and women

If you are a woman, you must not become pregnant during treatment with this medicine and for at least 6 months after the last dose.

If you are a man, you must take appropriate precautions to ensure your partner does not become pregnant during treatment with this medicine and for at least 3 months after the last dose.

Fertility

Men treated with this medicine are advised not to father a child during treatment and for 3 months after the last dose. Before starting treatment, you should seek advice on sperm preservation, as this medicine may cause permanent sterility.

Driving and use of machines

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

3. How to use Bendamustina Accord

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

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

You must not 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 be discontinued if the white blood cell (leukocyte) count and/or platelet count falls below certain levels. Treatment may be resumed when the leukocyte and platelet counts have increased.

Renal or hepatic impairment

Dosage adjustment may be necessary depending on the degree of liver function impairment (approximately 30% in cases of moderate hepatic impairment). Dosage adjustment is not required in cases of renal function impairment. Your doctor will decide whether a dosage adjustment is necessary.

How this medicine is administered

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

Your doctor will administer the infusion solution after its proper preparation. The solution is given into a vein as a short infusion lasting 30 to 60 minutes.

Duration of treatment

A specific duration of treatment with this medicine has not been established. The duration of treatment depends on the disease and the response to therapy.

If you have any concerns or questions about treatment with this medicine, speak with your doctor or nurse.

If you forget to use Bendamustina Accord

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

If you interrupt treatment with Bendamustina Accord

Your doctor will decide whether treatment should be interrupted or whether another preparation should be used.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them. Some of the reactions listed below may be detected during blood tests performed by your doctor.

Very rarely, tissue damage (due to cellular injury leading to premature cell death) has been observed following unintentional injection into the tissue surrounding blood vessels (extravascular). If the product is administered outside a blood vessel, there may be a burning sensation at the injection site. Consequences of such administration may include pain and skin healing problems.

The dose-limiting adverse effect of this medicine is bone marrow dysfunction, which usually resolves. Suppression of bone marrow function may lead to low levels of blood cells, which in turn may increase the risk of infection, anemia, or increased 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 pigment (hemoglobin: a protein in red blood cells that carries oxygen throughout the body)
• Reduction in platelet count (colorless blood cells involved in blood clotting)
• Infections
• Nausea
• Vomiting
• Inflammation of mucous membranes
• Increased blood creatinine concentration (a waste chemical produced by your muscles)
• Increased blood urea concentration (a waste chemical)
• Fever
• Fatigue
• Headache

Common (may affect up to 1 in 10 people):

• Bleeding (hemorrhage)
• Metabolic disturbance caused by dying cancer cells releasing their contents into the bloodstream
• Reduction in red blood cells, which may cause paleness, weakness, or difficulty breathing (anemia)
• Reduction in neutrophil count (a common type of white blood cell needed to fight infections)
• Hypersensitivity reactions, such as allergic skin inflammation (dermatitis) or urticaria
• Elevated liver enzymes AST/ALT, which may indicate inflammation or damage to liver cells
• Increased alkaline phosphatase enzyme (an enzyme mainly produced in the liver and bones)
• Increased bile pigment (a substance generated during normal breakdown of red blood cells)
• Low blood potassium levels (a nutrient necessary for the function of nerve and muscle cells, including those of the heart)
• Impaired cardiac function (cardiac dysfunction)
• Irregular heart rhythm (arrhythmia)
• Increase or decrease in blood pressure (hypotension or hypertension)
• Impaired lung function
• Diarrhea
• Constipation
• Mouth ulcers (stomatitis)
• Loss of appetite
• Hair loss
• Skin disorders
• Absence of menstrual periods (amenorrhea)
• Pain
• Insomnia
• Chills
• Dehydration
• Dizziness
• Itchy rash (urticaria)

Uncommon (may affect up to 1 in 100 people):

• Fluid accumulation in the sac surrounding the heart (fluid leakage into the pericardial space)
• Ineffective production of all blood cells (the spongy material inside your bones where blood cells are produced)
• Acute leukemia
• Heart attack, 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)
• Symptoms similar to anaphylactic reactions (anaphylactoid reactions)
• Somnolence
• Loss of voice (aphonia)
• Acute circulatory failure (failure in blood circulation, primarily of cardiac origin, resulting in inability to maintain oxygen and nutrient supply to tissues and removal of toxins)
• Skin redness (erythema)
• Skin inflammation (dermatitis)
• Itching (pruritus)
• Skin rash (maculopapular exanthem)
• Excessive sweating (hyperhidrosis)
• Reduced bone marrow function, which may make you feel unwell or appear in blood tests

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

• Primary atypical lung inflammation (pneumonia)
• Destruction of red blood cells
• Rapid drop in blood pressure, sometimes with skin reactions or rashes (anaphylactic shock)
• Altered sense of taste
• Sensory disturbances (paresthesia)
• Discomfort and pain in the limbs (peripheral neuropathy)
• Anticholinergic syndrome (inhibition of the physiological action of acetylcholine, especially as a neurotransmitter)
• Neurological disorders (diseases of the brain, spinal cord, and connecting nerves)
• Lack of coordination (ataxia)
• Brain inflammation (encephalitis)
• Increased heart rate (tachycardia)
• Inflammation of veins (phlebitis)
• Formation of fibrous tissue in the lungs (pulmonary fibrosis)
• Hemorrhagic inflammation of the throat (hemorrhagic esophagitis)
• Gastric or intestinal bleeding
• Infertility
• Multi-organ failure

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

• Kidney failure
• Liver failure
• Irregular and usually rapid heart rhythm (atrial fibrillation)
• Painful red or purplish rash or blisters spreading across mucous membranes (e.g., mouth or lips), particularly if you have previously experienced light sensitivity, respiratory infections (e.g., bronchitis), and/or fever
• Drug rash during combination treatment with rituximab
• Pneumonitis
• Bleeding from the lungs
• Excessive urination, even at night, and excessive thirst despite drinking fluids (nephrogenic diabetes insipidus)

There have been reports of tumors (myelodysplastic syndromes, AML, bronchial carcinoma) following treatment with bendamustine. A clear relationship with bendamustine could not be established.

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

Severe skin rashes including Stevens-Johnson syndrome and toxic epidermal necrolysis. These may appear as red, target-like spots or circular lesions, often with central blisters on the trunk, skin peeling, mouth ulcers, and sores in the 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 involvement (Drug Reaction with Eosinophilia and Systemic Symptoms, also known as DRESS or drug hypersensitivity syndrome).

If any of the adverse effects worsen, or if you notice any adverse effects not listed in this leaflet, please inform your doctor.

Reporting of adverse effects

If you experience any adverse effects, talk to your doctor, hospital pharmacist, or nurse, even if they are adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of 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 label and packaging after EXP or CAD. The expiry date refers to the last day of the month indicated.

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

Do not use this medicine if visible particles are observed in the solution or if the solution is not clear and colourless to yellowish.

After opening the vial

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

Once the vial has been opened, the product should 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 for 2 days at 2-8°C in polyethylene bags.

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

Minimizing the risk of contamination of the multidose vial during 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 injections or any other diluent, and return the multidose vial to the recommended storage condition of 2-8°C.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of medicines and packaging no longer required. This will help protect the environment.

6. Contents of the pack and other information

Composition of Bendamustine Accord

The active substance is bendamustine hydrochloride.

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

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

Each 4 ml vial contains 100 mg of bendamustine hydrochloride (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 1 ml and 4 ml amber glass vial with a chlorobutyl rubber stopper. The 1 ml vial is supplied with a red removable plastic cap and an aluminium seal, and the 4 ml vial is supplied with a red aluminium seal and 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

Manufacturer

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

Ul Lutomierska, 50

95-200 Pabianice

Poland

or

Accord Healthcare single member S.A.

64th Km National Road Athens, Lamia,

Schimatari, 32009, Greece

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

Date of the most recent review of this summary: June 2024

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es

This information is intended for healthcare professionals only:

As with all similar cytotoxic agents, nursing staff and physicians must take extreme safety precautions due to the potential genotoxic and carcinogenic properties of this preparation. Avoid inhalation (inspiration) and contact with skin and mucous membranes when handling Bendamustina Accord (wear gloves, protective clothing, and, if possible, a mask!). If any part of the body becomes contaminated, clean it carefully with water and soap, and rinse the eyes with 0.9% saline (isotonic) solution. If possible, it is recommended to work on a special safety cabinet (laminar flow hood) using a disposable, liquid-impermeable absorbent pad. Contaminated materials are cytotoxic waste. Please follow national regulations regarding the disposal of cytotoxic materials. Pregnant female staff should not handle cytotoxic agents.

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

1. Dilution

Aseptically withdraw the required volume from the 25 mg/ml vial of Bendamustina Accord. Dilute the recommended total dose of Bendamustina Accord 25 mg/ml with 0.9% sodium chloride solution to achieve a final volume of approximately 500 ml.

When diluting the product, it should be noted that the concentration (25 mg/ml) of bendamustine in Bendamustina Accord is higher than in the usual bendamustine concentrates obtained by reconstituting powdered bendamustine-containing medicines.

Bendamustina Accord 25 mg/ml must be diluted with 0.9% NaCl solution and not with any other injectable solution.

Dilution as recommended results in a clear, colorless to slightly yellow solution, practically free from visible particles.

1. Administration

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

The vials are for multiple use.

The product should be inspected before use. Visible particles in the solution or discoloration are signs of degradation. Degraded product must not be used.

Any unused medicine or waste material must be disposed of in accordance with local requirements.

Inadvertent injection into tissue outside blood vessels (extravasation) must be stopped immediately. The needle should be removed after brief aspiration. The affected tissue area should then be cooled. The arm should be elevated. Additional treatments such as corticosteroids do not provide a clear benefit.