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

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Bendamustina Accord 2.5 mg/ml powder for concentrate for solution for infusion EFG

Bendamustine hydrochloride

The name of your medicine is Bendamustina Accord 2.5 mg/ml powder for concentrate for solution for infusion, but it will be referred to as Bendamustina Accord throughout the rest of this leaflet.

Read the entire leaflet carefully before you start using this 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 must not be given to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the 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).

Bendamustina Accord 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, to 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 Bendamustina Accord is necessary during breastfeeding, you must stop breastfeeding (see section Pregnancy, breastfeeding, and fertility)
• if you have severe hepatic 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 a severe disorder of bone marrow function (bone marrow suppression) and severe abnormalities in the number of white blood cells and platelets in the blood
• if you have undergone a major surgical procedure within the previous 30 days before starting treatment
• if you have had any infection, especially if it was accompanied by a reduction in the number of white blood cells (leucopenia)
• in combination with yellow fever vaccines

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using Bendamustina Accord

• 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 Bendamustina Accord, before each treatment cycle, and at intervals between cycles.
• if you have infections. If you experience signs of infection such as fever or pulmonary symptoms, contact your doctor immediately.
• if you develop skin reactions during treatment with Bendamustina Accord. Skin reactions may increase in intensity.
• if you develop red or purplish painful rashes or blisters spread over the 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 notice pain in one side of your body or observe blood in your urine or reduced urine output. 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 Bendamustina Accord. Your doctor will ensure you are adequately hydrated and may give you other medications to prevent this from occurring.
• in case of severe allergic or hypersensitivity reactions, you should be monitored 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 very rare but serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML).

Use of Bendamustina Accord with other medicines

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

If Bendamustina Accord 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

Bendamustina Accord may cause genetic damage and has caused birth defects in animal studies. It must not be used during pregnancy unless clearly considered necessary 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 counselling is recommended.

If you are a woman of childbearing potential, you must use effective contraception 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 counselling.

Breastfeeding

Bendamustina must not be administered during breastfeeding. If you require treatment with this medicine 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 regarding sperm preservation, as this medicine may cause permanent sterility.

Driving and use of machines

No studies have been conducted on the effects on the ability to drive and use machines. 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.

Bendamustina Accord is administered intravenously over 30 to 60 minutes at various doses, either alone (monotherapy) or in combination with other medicines.

You cannot start treatment if your white blood cell count (leukocytes) 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 once 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 case of kidney function impairment. Your doctor will decide whether dosage adjustment is necessary.

How this medicine is administered

Bendamustina Accord must only be administered by physicians experienced in the treatment of tumors. Your doctor will administer the exact dose of Bendamustina Accord 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

There is no defined duration for treatment with Bendamustina Accord. The duration of treatment depends on the disease and the response to therapy.

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

If you forget to use Bendamustina Accord

If you miss a dose of Bendamustina Accord, 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 an alternative 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 will experience them. Some of the reactions listed below may be detected by blood tests performed by your doctor.

The following frequency categories are used to classify adverse reactions:

Very common: may affect more than 1 in 10 people
Common: may affect up to 1 in 10 people
Uncommon: may affect up to 1 in 100 people
Rare: may affect up to 1 in 1,000 people
Very rare: may affect up to 1 in 10,000 people
Not known: frequency cannot be estimated from the available data

In very rare cases, 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, a burning sensation may occur at the injection site. Consequences of such administration may include pain and impaired skin healing.

The dose-limiting adverse effect of Bendamustina Accord is bone marrow dysfunction, which is usually reversible. Suppression of bone marrow function may lead to low blood cell counts, which in turn may increase the risk of infection, anemia, or bleeding.

Very common:

• Decrease in white blood cell count (blood defenses)
• Decrease in red blood pigment (hemoglobin: a protein in red blood cells that carries oxygen throughout the body)
• Decrease 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 muscles)
• Increased blood urea concentration (a waste chemical)
• Fever
• Fatigue
• Headache

Common:

• Bleeding (hemorrhage)
• Metabolic disturbances caused by dying cancer cells releasing their contents into the bloodstream
• Decrease in red blood cells, which may cause pale skin, weakness, or difficulty breathing (anemia)
• Decrease in neutrophil count (a common type of white blood cell needed to fight infections)
• Hypersensitivity reactions, such as allergic skin inflammation (dermatitis) or hives
• Increased 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)
• Changes in 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:

• Fluid accumulation in the sac surrounding the heart (pericardial effusion)
• Ineffective production of blood cells (in the spongy tissue inside the bones where blood cells are formed)
• Acute leukemia
• Heart attack, chest pain (myocardial infarction)
• Heart failure

Rare:

• Blood infection (sepsis)
• Severe allergic and hypersensitivity reactions (anaphylactic reactions)
• Symptoms similar to anaphylactic reactions (anaphylactoid reactions)
• Drowsiness
• Loss of voice (aphonia)
• Acute circulatory failure (failure of blood circulation, primarily of cardiac origin, resulting in inadequate delivery of oxygen and nutrients to tissues and impaired removal of toxins)
• Skin redness (erythema)
• Skin inflammation (dermatitis)
• Itching (pruritus)
• Skin rash (macular exanthema)
• Excessive sweating (hyperhidrosis)
• Reduced bone marrow function that may make you feel unwell or show up in blood tests

Very rare:

• Primary atypical lung inflammation (pneumonia)
• Destruction of red blood cells
• Rapid drop in blood pressure, sometimes accompanied by skin reactions or rashes (anaphylactic shock)
• Altered sense of taste
• Altered sensation (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)
• Tissue formation in the lungs (pulmonary fibrosis)
• Hemorrhagic inflammation of the throat (hemorrhagic esophagitis)
• Gastric or intestinal bleeding
• Infertility
• Multi-organ failure

Not known:

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

There have been reports of tumors (myelodysplastic syndromes, acute myeloid leukemia, 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 reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis. These may appear as red, target-like spots or circular patches, often with central blisters on the trunk, skin peeling, and ulcers in the mouth, 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 Bendamustina 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. The expiry date refers to the last day of the month indicated.

This medicine does not require special storage temperature conditions.

Store in the original outer packaging to protect from light.

Check the expiry date before opening or preparing the solution.

Infusion solutions prepared correctly according to the instructions listed at the end of this leaflet are stable in polyethylene bags at 25°C for 3.5 hours and at 2°C – 8°C for 2 days. Bendamustina Accord does not contain preservatives. Therefore, the solution must not be used beyond these time limits.

The user is responsible for maintaining aseptic conditions.

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

6. Contents of the pack and other information

Composition of Bendamustine Accord

The active substance is bendamustine hydrochloride.

One vial contains 25 mg of bendamustine hydrochloride (as monohydrate bendamustine hydrochloride).

One vial contains 100 mg of bendamustine hydrochloride (as monohydrate bendamustine hydrochloride).

After reconstitution, 1 ml of concentrate contains 2.5 mg of bendamustine hydrochloride (as monohydrate bendamustine hydrochloride).

The other ingredient is mannitol.

Appearance of the product and contents of the pack

Amber glass vials with bromobutyl rubber stoppers and aluminium flip-off caps.

Bendamustine Accord is marketed in packs containing 5, 10 and 20 vials of 25 mg bendamustine hydrochloride and 1 and 5 vials of 100 mg bendamustine hydrochloride.

Not all pack sizes may be marketed.

Marketing Authorization 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 authorized in the Member States of the European Economic Area under the following names:

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

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Medical Devices (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 exercise extreme caution 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, carefully clean it with water and soap, and rinse eyes with 0.9% saline (isotonic) solution. When possible, it is recommended to work on a special safety cabinet (laminar flow hood) using an impermeable, absorbent disposable pad. Contaminated materials are cytostatic waste. Please follow national regulations regarding the disposal of cytostatic material! Pregnant female staff should not handle cytostatics.

The ready-to-use solution must be prepared by dissolving the contents of one vial of Bendamustina Accord exclusively in water for injection, as described below:

1. Preparation of the concentrate
   • First, dissolve one vial of Bendamustina Accord containing 25 mg of bendamustine hydrochloride in 10 ml by gently agitating.

• First, dissolve one vial of Bendamustina Accord containing 100 mg of bendamustine hydrochloride in 40 ml by gently agitating.

2. Preparation of the infusion solution

Immediately after obtaining a clear solution (usually within 5 to 10 minutes), dissolve the total recommended dose of Bendamustina Accord in 0.9% saline solution (isotonic) to achieve a final volume of approximately 500 ml. Bendamustina Accord must not be dissolved in other infusion or injection solutions. Bendamustina Accord must not be mixed in the same infusion with other substances.

3. Administration

The solution is administered by intravenous infusion over 30–60 minutes. The vials are for single use only. Any unused medicine and all materials that have come into contact with it must be disposed of in accordance with local regulations.

Inadvertent injection into tissues outside blood vessels (extravasation) must be stopped immediately. The needle should be removed after a brief aspiration. The affected tissue area should then be cooled. The arm should be elevated. The benefit of additional treatments such as corticosteroids is unclear (see section 4).