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

Bendamustine hydrochloride

Read this 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, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people,

even if they have the same symptoms as you, because it may harm them.

• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

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

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

Bendamustina Hikma 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 high-dose chemotherapy and autologous progenitor cell transplantation or treatments containing thalidomide or bortezomib are not suitable for you

2. What you need to know before using Bendamustina Hikma

Do not use Bendamustina Hikma

• 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, breastfeeding must be discontinued (see section on pregnancy, breastfeeding, and fertility).

• If you have severe hepatic dysfunction (damage to the liver's functional 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 major surgery within the previous 30 days before starting treatment.

• If you have had any infection, especially if accompanied by a reduced number of white blood cells (leucopenia).

• In combination with yellow fever vaccines.

Warnings and precautions

Talk to your doctor 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 show signs of infection, such as fever or respiratory symptoms, contact your doctor.

• 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).

• If you experience skin reactions during treatment with bendamustine. Skin reactions may increase in intensity.

• Contact your doctor if you notice any suspicious changes in the skin, as use of this medicine may increase the risk of certain types of non-melanoma skin cancer.

• If you develop widespread, painful red or purple rashes and blisters and/or other lesions starting in the mucous membranes (e.g., mouth and lips), particularly if you have previously had light sensitivity, respiratory 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.

Use of Bendamustina Hikma with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

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 are planning 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 must 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 treatment on your unborn child, and genetic counseling is recommended.

If you are a woman of childbearing potential, you must use effective contraception before and during treatment with this medicine. If you become pregnant during treatment with this medicine, you must inform your doctor immediately and seek genetic counseling.

Breastfeeding

This medicine must not be administered during breastfeeding. If you require treatment with bendamustine during breastfeeding, you must discontinue breastfeeding.

Consult your doctor before starting to use any medicine.

Fertility

Men treated with this medicine are advised not to father a child during treatment and for 6 months after treatment. Before starting treatment, you should seek advice on sperm preservation, as this medicine may cause permanent sterility.

If you are a man, you must not father a child during treatment with this medicine and for 6 months after treatment. There is a risk that treatment with this medicine may cause sterility; you may wish to seek advice on sperm preservation before starting treatment.

Driving and use of machines

The effect of this medicine on the ability to drive and operate machinery is significant. Do not drive or operate machinery if you experience adverse effects such as dizziness or lack of coordination.

3. How to use Bendamustina Hikma

Always use this medicine exactly as your doctor or pharmacist has explained to you. Check 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 cannot start treatment if your white blood cell (leukocyte) count and/or platelet count are 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) 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 (a 30% reduction in case of moderate liver impairment). Dosage adjustment is not required in case of impaired kidney function. 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 bendamustine and take the necessary precautions.

Your doctor will administer the infusion solution after it has been prepared as prescribed. 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 treatment.

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

If you forget to use Bendamustina Hikma

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

If you interrupt treatment with Bendamustina Hikma

Your doctor will decide whether treatment should be interrupted or if 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 will experience them. Some of the following results may be detected through tests performed by your doctor:

The following frequencies are used to assess 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 available data

In very rare cases, tissue damage (necrosis) has been observed following unintentional injection into the tissue surrounding blood vessels (extravascular). A burning sensation at the injection site may indicate administration outside the vessel. Consequences of such administration may include pain and skin defects with poor healing.

The dose-limiting adverse effect of this medicine is impairment of bone marrow function, which usually returns to normal after treatment ends. Suppression of bone marrow function may lead to low blood cell counts, which in turn may increase the risk of infection, anemia, or a higher risk of bleeding.

Very common adverse effects:

• Decrease in white blood cell count (cells that fight disease in your blood)
• 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
• Headache
• Increased blood creatinine concentration (a waste chemical produced by your muscles)
• Increased blood urea concentration (a waste chemical)
• Fever
• Fatigue

Common adverse effects:

• Bleeding (hemorrhage)
• Metabolic disturbances caused by the release of contents from dying cancer cells into the bloodstream
• Reduction in red blood cells, which may cause pale skin, weakness, or difficulty breathing (anemia)
• Reduction in neutrophil count (a type of white blood cell important for fighting infections)
• Hypersensitivity reactions, such as allergic skin inflammation (dermatitis) or hives (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 the 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 (dysfunctional) cardiac function
• 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 skin rash (urticaria)

Uncommon adverse effects:

• Fluid accumulation in the sac surrounding the heart (fluid leakage into the pericardial space)
• Ineffective production of all blood cells by the bone marrow (the spongy tissue inside bones where blood cells are produced)
• Acute leukemia
• Heart attack, chest pain (myocardial infarction)
• Heart failure

Rare adverse effects:

• Blood infection (sepsis)
• Severe allergic and hypersensitivity reactions (anaphylactic reactions)
• Decreased bone marrow function, which may make you feel unwell or show up in blood tests
• Symptoms similar to anaphylactic reactions (severe allergy) (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 toxin removal)
• Skin redness (erythema)
• Skin inflammation (dermatitis)
• Itching (pruritus)
• Skin rash (maculopapular exanthem)
• Excessive sweating (hyperhidrosis)

Very rare adverse effects:

• 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
• Altered sensation (paresthesia)
• Weakness and pain in limbs (peripheral neuropathy)
• Serious condition causing blockade of specific receptors in the nervous system (anticholinergic syndrome)
• Disorders of the nervous system
• Lack of coordination (ataxia)
• Brain inflammation (encephalitis)
• Increased heart rate (tachycardia)
• Vein inflammation (phlebitis)
• Formation of fibrous tissue in the lungs (pulmonary fibrosis)
• Hemorrhagic inflammation of the esophagus (hemorrhagic esophagitis)
• Gastric or intestinal bleeding
• Infertility
• Multi-organ failure

Adverse effects with unknown frequency:

• Liver failure
• Kidney failure
• Irregular and often rapid heartbeats (atrial fibrillation)
• Painful widespread red or purple rashes and blisters and/or other lesions beginning on mucous membranes (e.g., mouth and lips), particularly if there has been prior light sensitivity, respiratory tract infections (e.g., bronchitis), and/or fever
• Drug rash during combination therapy with rituximab
• 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 secondary tumors (myelodysplastic syndromes, AML, bronchial carcinoma) following treatment with this medicine. A clear relationship with this medicine 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 macules or circular red spots resembling targets, 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, enlarged lymph nodes, and other organ abnormalities (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 other type of adverse effect, consult your doctor or nurse, even if they are possible adverse effects not listed in this leaflet. You may also report them directly via www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Bendamustine Hikma

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 the carton following EXP. The expiry date refers to the last day of the month indicated.

Store below 25 °C. Keep the vial in the outer packaging to protect the contents from light.

Note on the shelf life after opening or preparation of the solution.

Infusion solution

After reconstitution and dilution, chemical and physical in-use stability has been demonstrated for 3.5 hours at 25°C / 60% RH and for 2 days at 2°C – 8°C in polyethylene bags.

From a microbiological standpoint, the solution should be used immediately. Otherwise, the storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2°C – 8°C, unless reconstitution/dilution takes place under validated and controlled aseptic conditions.

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 containers you no longer need. These measures will help protect the environment.

6. Package Contents and Additional Information

Composition of Bendamustina Hikma

The active substance is bendamustine hydrochloride.

One vial contains 25 mg or 100 mg of bendamustine hydrochloride (as monohydrate bendamustine hydrochloride).

After reconstitution, 1 ml of concentrate contains 2.5 mg of bendamustine hydrochloride.

The other component is mannitol.

Appearance of the Product and Contents of the Container

Amber glass vials with a rubber stopper and flip-off aluminium cap.

White, crystalline powder.

This medicinal product is available in pack sizes containing 1 or 5 vials.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Hikma Farmacêutica (Portugal), S.A.
Estrada do Rio da Mó, 8 - Terrugem
2705-906 Sintra
Portugal

Manufacturer

Thymoorgan GmbH Pharmazie
Schiffgraben, 23
38690 Goslar
Germany

For further information regarding this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Hikma España, S.L.U.
Calle Anabel Segura nº11, Edificio A, planta 1ª, oficina 2
28108 - Alcobendas, Madrid
Spain

This medicinal product is authorized in the European Economic Area member states under the following names:

Germany: Bendamustin Hikma 2,5mg/ml Pulver für ein Konzentrat zur Herstellung einer Infusionslösung
Austria: Bendamustin Hikma 2,5mg/ml Pulver für ein Konzentrat zur Herstellung einer Infusionslösung
Spain: Bendamustina Hikma 2,5mg/ml Polvo para concentrado para solución para perfusión EFG
France: BENDAMUSTINE HIKMA 2,5mg/mL, poudre pour solution à diluer pour perfusion
Italy: Bendamustina Hikma
Portugal: Bendamustina Hikma
United Kingdom (Northern Ireland): Bendamustine 2.5mg/ml Powder for concentrate for solution for infusion

Date of the most recent review of this leaflet: October 2025

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) at 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 and contact with skin and mucous membranes when handling this medicinal product (wear gloves, protective clothing, and, if possible, a mask!). If any part of the body becomes contaminated, wash carefully with water and soap, and rinse eyes with 0.9% saline (isotonic) solution. Whenever possible, it is recommended to work on a special safety cabinet (laminar flow hood) using a disposable, liquid-impermeable absorbent pad. Contaminated materials are cytostatic waste. Please follow national regulations regarding the disposal of cytostatic materials! Pregnant female staff should not handle cytostatics.

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

1. Preparation of the concentrate

   • First, dissolve the contents of a vial containing 25 mg of bendamustine hydrochloride in 10 ml, by agitation.
   • First, dissolve the contents of a vial containing 100 mg of bendamustine hydrochloride in 40 ml, by agitation.

2. Preparation of the infusion solution

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

3. Administration

The solution should be administered by intravenous infusion over 30–60 minutes.

Vials are for single use only.

Any unused portion remaining in the vial or materials must be discarded according to local regulations.

In case of extravasation, infusion must be stopped immediately. The needle should be withdrawn after brief aspiration. The affected tissue area should then be cooled. The arm should be elevated. It is unclear whether additional treatment, such as the use of corticosteroids, is beneficial (see section 4).