Prospecto: information for the user

Bendamustine Baxter2.5mg/mlpowder for concentrate for solution for infusion EFG

Bendamustine, hydrochloride

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.

-This medicine has been prescribed only for you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.

• If you experience adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section4.

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

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

3.How to use Bendamustine Baxter

1. Adverse effects
2. Storage of Bendamustine Baxter
3. Contents of the package and additional information

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

Bendamustina Baxteris 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 with thalidomide or bortezomib are not suitable for you.

No use Bendamustina Baxter

-if you are allergic to bendamustine hydrochloride or any of the other ingredients in this medication (listed in section6);

-if you are breastfeeding; if you need treatment with Bendamustina Baxter while breastfeeding, you should stop breastfeeding (see section “Warnings and precautions” about breastfeeding);

-if you have severe liver dysfunction (liver cell damage);

-if you have yellowing of the skin or the white part of the eyes caused by liver or blood problems (jaundice);

-if you have severe bone marrow dysfunction (bone marrow depression) and significant changes in the number of white blood cells and platelets in the blood;

-if you have had major surgery within 30days before starting treatment;

-if you have had any infections, especially if accompanied by a reduction in the number of white blood cells (leucopenia);

-in combination with yellow fever vaccines.

Warnings and precautions

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 detect any suspicious changes in the skin, as the use of this medication may increase the risk of certain types of skin cancer (non-melanoma skin cancer).

Consult your doctor, pharmacist, or nurse before starting to use Bendamustina Baxter:

• if your bone marrow has been reduced in its ability to replace blood cells. Your doctor should determine the number of white blood cells and platelets in your blood before starting treatment withbendamustine, before each treatment cycle, and between cycles;
• if you have infections. If you have symptoms of infection, such as fever or respiratory symptoms, you should contact your doctor;
• if you have skin reactions during treatment withbendamustine. Skin reactions may increase in intensity;
• if you have painful red or purple rashes that spread and blisters or other lesions that appear on mucous membranes (e.g., mouth and lips), especially if you have had previous sensitivity to light, respiratory infections (e.g., bronchitis), and/or fever;
• if you have a heart condition (e.g., heart attack, chest pain, severe heart rhythm disorders);
• if you experience pain in your 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 may cause kidney failure and heart problems within 48hours after the first dose ofbendamustine. Your doctor will ensure that you are well-hydrated and will give you other medications to prevent this from happening;
• in case of severe allergic reactions or hypersensitivity. You should pay attention to reactions to infusion after your first treatment cycle.

Use of Bendamustina Baxter with other medications

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

Ifbendamustinais used in combination with medications that inhibit blood cell formation in the bone marrow, the effect on the bone marrow may be intensified.

Ifbendamustinais 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).

Bendamustinashould not be used with fluvoxamine, ciprofloxacin, aciclovir, or cimetidine due to the possibility of interactions.

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

Bendamustinemay cause genetic damage and has caused malformations in animal studies. It should not be used during pregnancy unless your doctor advises you to do so. If you receive treatment, you should consult your doctor about the risk of possible adverse effects on the fetus. Genetic counseling is recommended.

If you are a fertile woman, you should use effective contraceptive methods before and during treatment withbendamustina. If you become pregnant during treatment withbendamustina, you should inform your doctor immediately and undergo genetic counseling.

Breastfeeding

Bendamustinashould not be administered during breastfeeding. If you need treatment withbendamustinawhile breastfeeding, you should stop breastfeeding.

Consult your doctor or pharmacist before using any medication.

Fertility

Men who receive treatment withbendamustinashould not have children during treatment or in the 6months following the end of treatment. Before starting treatment, you should be advised about sperm conservation due to the possibility of permanent sterility.

Driving and operating machines

The influence of bendamustinaon your ability to drive and operate machines is important. Do not drive or operate machines if you experience side effects such as drowsiness, lack of coordination, or peripheral nervous system disorders.

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Bendamustina Baxteris administered through a vein for 30 to 60minutes in various doses, either alone (monotherapy) or combined with other medications.

Do not start treatment if the number of white blood cells (leukocytes) and/or platelets falls below certain levels.

Your doctor will determine these values periodically.

Chronic Lymphocytic Leukemia

Bendamustina Baxter100mg per square meter of body surface area (calculated based on weight and height) on days1 and 2.

This cycle will be repeated every 4weeks and up to 6times.

Non-Hodgkin Lymphomas

Bendamustina Baxter120mg per square meter of body surface area (calculated based on weight and height) on days1 and 2.

This cycle will be repeated every 3weeks at least 6times.

Multiple Myeloma

Bendamustina Baxter120-150mg per square meter of body surface area (calculated based on weight and height) on days1 and 2.

Prednisone 60mg per square meter of body surface area (calculated based on weight and height) on days1 and 2 administered intravenously or orally on days1 to 4.

This cycle will be repeated every 4weeks at least 3times.

Treatment should be interrupted if the number of white blood cells (leukocytes) and/or platelets falls below certain levels. Treatment may be resumed when the number of white blood cells and platelets has increased.

Renal or Hepatic Insufficiency

Depending on the degree of hepatic insufficiency, it may be necessary to adjust the dose (a 30% reduction in case of moderate hepatic insufficiency). No dose adjustment is necessary in case of renal insufficiency. Your doctor will decide if a dose adjustment is necessary.

How to Administer

Only experienced doctors in the treatment of tumorsshould administer Bendamustina Baxter. Your doctor will administer the exact dose ofBendamustina Baxterand take the necessary precautions.

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

Treatment Duration

No specific duration of treatment withBendamustina Baxterhas been defined. Treatment duration depends on the disease and response to treatment.

If you are concerned about anything or have any doubts about treatment withBendamustina Baxter, speak with your doctor or nurse.

Use in Children and Adolescents

The safety and efficacy of bendamustine hydrochloride in children have not yet been established. Currently available data are insufficient to make a dosage recommendation.

If You Miss a Dose of Bendamustina Baxter

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

If You Interrupt Treatment with Bendamustina Baxter

Your treating doctor will decide whether to interrupt treatment or switch to a different preparation.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Some of the manifestations listed below may be observed after tests performed by your doctor.

In rare cases, tissue deterioration (necrosis) has been observed after extravasation ofbendamustineinto the tissue surrounding blood vessels (extravascular). If the medicine leaks out of a vein, you may feel a burning sensation at the site of the needle insertion. Consequences may include pain and poorly healed skin lesions.

The dose-limiting side effect ofbendamustineis bone marrow insufficiency, which usually normalizes after treatment. Suppression of bone marrow function may lead to a decrease in the number of blood cells, which in turn may increase the risk of infection, anemia, or bleeding.

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

• Infections.
• Decrease in the number of white blood cells (blood cells that fight diseases).
• Decrease in the number of platelets (colorless blood cells that help blood coagulation).
• Nausea.
• Vomiting.
• Mucous membrane inflammation.
• Fatigue.
• Fever.
• Decrease in red blood cell pigment (hemoglobin: a protein in red blood cells that transports oxygen throughout the body).
• Increased creatinine levels (a chemical waste product produced by muscle) in the blood.
• Increased urea levels (a chemical waste product) in the blood.
• Headache.

Common (may affect up to 1 in 10 people)

• Metabolic disorder caused by dying cancer cells, which release their contents into the bloodstream (tumor lysis syndrome).
• Bleeding (hemorrhage).
• Decrease in red blood cells, which may cause pale skin and weakness or difficulty breathing (anemia).
• Decrease in neutrophils (a common type of white blood cell necessary to fight infections).
• Hypersensitivity reactions, such as skin inflammation (dermatitis) or urticaria.
• Insomnia.
• Cardiac function disorder (such as angina pectoris).
• Arrhythmia.
• Low or high blood pressure (hypotension or hypertension).
• Pulmonary function disorder.
• Diarrhea.
• Constipation.
• Mouth ulcers (stomatitis).
• Hair loss.
• Skin changes.
• Amenorrhea (absence of menstruation).
• Pain.
• Chills.
• Dehydration.
• Dizziness.
• Itching (pruritus).
• Loss of appetite.
• Increased AST/ALT liver enzymes (may indicate liver cell inflammation or damage).
• Increased alkaline phosphatase enzyme (a liver enzyme produced mainly in the liver and bones).
• Increased bilirubin levels (a substance produced during normal red blood cell breakdown).
• Low potassium levels (a nutrient necessary for nerve and muscle cell function, including heart cells) in the blood.

Uncommon (may affect up to 1 in 100 people)

• Accumulation of fluid in the sac surrounding the heart (pericardial effusion).
• Ineffective production of blood cells in the bone marrow (spongy tissue inside bones where blood cells are generated).
• Acute leukemia.
• Myocardial infarction (heart attack), chest pain.
• Heart failure.

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

• Blood infection (sepsis).
• Severe allergic and hypersensitivity reactions (anaphylactic reactions).
• Similar reactions to anaphylactic reactions (anaphylactoid reactions).
• Decreased bone marrow function, which may cause malaise or abnormal blood test results.
• Somnolence.
• Loss of voice (aphonia).
• Acute circulatory failure (circulatory failure primarily of cardiac origin with inability to maintain oxygen and nutrient supply to tissues and removal of toxins).
• Redness of the skin (erythema).
• Skin inflammation (dermatitis).
• Itching (pruritus).
• Macular exanthema (skin rash).
• Excessive sweating (hyperhidrosis).

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

• Atypical primary inflammation of the lungs (pneumonia).
• Red blood cell breakdown.
• Rapid drop in blood pressure, sometimes with skin reactions or rashes (anaphylactic shock).
• Alteration of taste.
• Alteration of sensitivity (paresthesia).
• Discomfort and pain in the extremities (peripheral neuropathy).
• Severe condition causing blockage of specific receptors in the nervous system.
• Nervous system disorders.
• Coordination disorder (ataxia).
• Encephalitis (inflammation of the brain).
• Increased heart rate (tachycardia).
• Phlebitis (inflammation of the veins).
• Pulmonary fibrosis (formation of tissue in the lungs).
• Esophageal inflammation with bleeding (esophagitis hemorrágica).
• Gastrointestinal or intestinal bleeding.
• Infertility.
• Multi-organ failure.

Frequency unknown (cannot be estimated from available data)

• Liver insufficiency.
• Renal insufficiency.
• Irregular and often rapid heart rate (atrial fibrillation).
• Red or purple painful eruptions that spread and blisters or other lesions that appear on mucous membranes (p.e.g., mouth and lips), particularly if you have had previous sensitivity to light, respiratory tract infections (p.e.g., bronchitis) and/or fever.
• Medication rash in combination therapy with rituximab.
• Pneumonitis.
• Pulmonary bleeding.

Cases of tumors (myelodysplastic syndromes, acute myeloid leukemia, bronchial carcinoma) have been described after treatment withbendamustine. A clear relationship withbendamustinecould not be established.

Consult your doctor or seek immediate medical attention if you observe any of the following side effects (frequency unknown):

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

Widespread rash, high body temperature, swollen lymph nodes, and involvement of other body organs (drug reaction with eosinophilia and systemic symptoms, also known as DRESS or drug hypersensitivity syndrome).

If you consider any of the side effects you are experiencing to be severe or if you observe any side effect not mentioned in this prospectus, inform your doctor.

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor, pharmacist, or nurse, even if it is a possible adverse reaction not listed in this prospectus. You can also report them directly through thenational notification systemSistema Español de Farmacovigilancia de Medicamentos de Uso Humano:www.notificaRAM.es

By reporting adverse reactions, 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 the box after CAD. The expiration date is the last day of the month indicated.

No special storage conditions are required.

Note on the validity period after opening or preparation of the solution

Solutions for infusion prepared according to the guidelines mentioned above are stable in Viaflo bags composed of polypropylene, polyamide, and polyethylene for 3.5 hours at room temperature and for 2 days if stored in the refrigerator.Bendamustina Baxter does not contain preservatives. From a microbiological point of view, the medication should be used immediately. Otherwise, the previous storage times and conditions before use are the responsibility of the user and should normally not exceed 24 hours at a temperature between 2 and 8°C, unless reconstitution/dilution (etc.) has taken place in controlled and validated aseptic conditions.Once these times have elapsed, the solutions should not be used.

It is the user's responsibility to maintain aseptic conditions.

Medications should not be disposed of through the drains or trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Bendamustine Baxter

• The active ingredient is bendamustine hydrochloride.

Cada vial contains 25mg of bendamustine hydrochloride.

Cada vial contains 100mg of bendamustinehydrochloride.

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

• The other component is mannitol.

Appearance of the product and contents of the package

Amber-colored glass vials with a dark gray bromobutyl rubber stopper and an aluminum cap.

The powder is white to off-white and lyophilized.

Bendamustine Baxteris marketed in packages containing

1, 5, 10, and 20vials of 20ml with 25mg of bendamustine hydrochloride and 1 and 5vials of 50ml with 100mg of bendamustine hydrochloride.

Only some package sizes may be marketed.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Baxter, S.L.

Pouet de Camilo, 2

46394 Ribarroja del Turia (Valencia)

Spain

Responsible for manufacturing

Baxter Oncology GmbH

Kantstrasse 2

33790 Halle/Westfalen

Germany

This medicinal product is authorized in the member states of theEuropean Economic Areawith the following names:

GermanyBendamustin Baxter 2.5 mg/ml Powder for a concentrate for the preparation of an infusion solution

SpainBendamustine Baxter 2.5mg/ml powder for concentrate for solution for infusion EFG

FranceBendamustine Baxter 2.5 mg/ml powder for solution to be diluted for infusion

NetherlandsBendamustine Baxter 2.5 mg/ml powder for concentrate for solution for infusion

United KingdomBendamustine hydrochloride 2.5 mg/ml Powder for concentrate for solution for infusion

Last review date of this leaflet:December 2020

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This information is intended solely for healthcare professionals:

As with all similar cytotoxics, nursing and medical staff must exercise extreme caution due to the potential genotoxicity and carcinogenicity of the preparation. Avoid inhalation (breathing) and contact with the skin and mucous membranes when handlingBendamustine Baxter(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 flush the eyes with 9mg/ml sodium chloride (0.9%) (isotonic) injectable solution. If possible, it is recommended to work on a special safety workbench (laminar flow) with a disposable impermeable to liquids.

Contaminated items are cytostatic waste. Please follow national regulations for the disposal of cytostatic material. Pregnant women should not work with cytotoxics.

The ready-to-use solution must be prepared by dissolving the contents of a vial ofBendamustine Baxterexclusively in water for injection, as indicated below:

1.Preparation of the concentrate

•First, dissolve a vial ofBendamustine Baxtercontaining 25mg of bendamustine hydrochloride in 10ml, shaking it.

•First, dissolve a vial ofBendamustine Baxtercontaining 100mg of bendamustine hydrochloride in 40ml, shaking it.

2.Preparation of the infusion solution

Once a transparent solution(usually within 5 to 10minutes) is obtained, immediately dilute the total recommended dose ofBendamustine Baxterwith 9mg/ml sodium chloride (0.9%) (isotonic) injectable solution to obtain a final volume of approximately 500ml.Bendamustine Baxtershould not be diluted with other infusion solutions or injectables.Bendamustine Baxtershould not be mixed with other substances in infusion.

3.Administration

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

The vials are for single use.

Disposal of unused medication and all materials that have come into contact with it, will be carried out in accordance with local regulations.

If, unintentionally, the product is injected into the tissue surrounding the blood vessels (extravasal injection), the infusion should 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. It is unclear whether the use of additional treatments (such as corticosteroids) is beneficial (see section4).

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

The infusion solutions prepared in accordance with the guidelines above are stable in Viaflo bags composed of polypropylene, polyamide, and polyethylene for 3.5hoursat room temperature and 60% relative humidity, andfor2daysif storedin the refrigerator.Bendamustine Baxterdoes not contain preservatives. From a microbiological point of view, the medicinal product should be used immediately. Otherwise, the times and conditions of storage prior to use are the responsibility of the user and should not normally exceed 24hours at a temperature between 2 and 8°C, unless reconstitution/dilution (etc.) has taken place in controlled and validated aseptic conditions.Once these times have elapsed, the solutions should not be used.