Prospect: information for the user

Bendamustine Aurovitas 2.5 mg/ml powder 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 questions, consult your doctor, pharmacist, or nurse.

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

-If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospect. See section 4.

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

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

3.How to use Bendamustine Aurovitas

4.Possible adverse effects

5.Storage of Bendamustine Aurovitas

6.Contents of the package and additional information

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

Bendamustinais 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 talidomide or bortezomib are not suitable for you.

No use Bendamustina Aurovitas

•if you are allergic to hydrochloride bendamustine or any of the other components of this medication (listed in section 6).

•during breastfeeding; if you need treatment with hydrochloride bendamustine during breastfeeding, you must suspend it (see section Pregnancy, breastfeeding and fertility).

•if you have severe liver dysfunction (liver cell functional damage).

•if you have yellowish skin or white eye discoloration 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 an infection, especially if it has been 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 beforestarting to usebendamustine.

•in case your bone marrow has reduced ability to replace blood cells. You must measure the number of white blood cells and platelets in the blood before starting treatment with hydrochloride bendamustine, before each treatment cycle and between cycles.

•in case of infections. If you have signs of infection, such as fever or respiratory symptoms, you must contact your doctor.

•if you have skin reactions during treatment with hydrochloride bendamustine. Skin reactions can increase in intensity.

•in case of widespread painful red or purple rashes and blisters and/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 disease (e.g., heart attack, chest pain, severe heart rhythm disorders).

•if you experience side pain or if you notice blood in your urine or if you urinate less. If your disease is very severe, it is possible that your body cannot 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 hydrochloride bendamustine. 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. You must pay attention to reactions after your first treatment cycle.

•at any time during or after treatment, inform your doctor immediately if you notice or someone notices in you: memory loss, cognitive difficulties, difficulty walking or vision loss. These symptoms may be due to a rare but severe 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 developing certain types of skin cancer (non-melanoma skin cancer).

Other medications and Bendamustina Aurovitas

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

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

Cytostatics can 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

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

If you are a fertile woman, you must use effective contraceptive methods before and during treatment with hydrochloride bendamustine. If you become pregnant during treatment with hydrochloride bendamustine, you must inform your doctor immediately and seek genetic counseling.

Breastfeeding

This medication should not be administered during breastfeeding. If you need treatment with hydrochloride bendamustine during breastfeeding, you must suspend it.

Consult your doctor or pharmacist before using any medication.

Fertility

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

Driving and operating machinery

Hydrochloride bendamustine has a significant influence on your ability to drive and operate machinery. Do not drive or operate machinery if you experience side effects such as dizziness or lack of coordination.

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

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

You will not be able to start treatment if your white blood cell count (leukocytes) and/or platelet count is below the determined levels.

Your doctor will measure these values periodically.

Chronic Lymphocytic Leukemia

Non-Hodgkin Lymphomas

Multiple Myeloma

Treatment will end if the white blood cell count (leukocytes) and/or platelet count falls below the determined levels. Treatment may be resumed when the leukocyte and platelet count has increased.

Renal or Hepatic Insufficiency

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

Bendamustine hydrochloride can only be administered by experienced doctors in tumor treatment. Your doctor will administer the exact dose of bendamustine hydrochloride and take necessary precautions.

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

Treatment Duration

The exact duration of treatment with bendamustine hydrochloride 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 bendamustine hydrochloride, talk to your doctor or nurse.

If You Miss a Dose of Bendamustina Aurovitas

If you forget a dose of bendamustine hydrochloride, your doctor will usually proceed with the normal dosing schedule.

If You Interrupt Treatment with Bendamustina Aurovitas

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

If you have any other doubts 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 findings listed below may be found after tests performed by your doctor.

To evaluate side effects, the following definitions are used, based on frequency:

In very rare cases, tissue degradation (necrosis) has been observed after the extravasation of hydrochloride bendamustine into the tissue surrounding blood vessels (extravascular). If the product leaks out of a vein, there may be a burning sensation at the site of the needle insertion. The consequences may be pain and skin healing problems.

The dose-limiting side effect of hydrochloride bendamustine is bone marrow dysfunction, which usually normalizes. Bone marrow suppression can lead to a reduction in blood cell counts, which in turn may increase the risk of infection, anemia, or bleeding.

Very common:

•Low white blood cell counts (cells that fight diseases in your blood).

•Reduction of red blood cell pigment (hemoglobin: a protein in red blood cells that carries oxygen throughout the body).

•Low platelet counts (colorless blood cells that help blood clotting).

•Infections.

•Nausea.

•Vomiting.

•Mucous membrane inflammation.

•Headache.

•Increased blood creatinine concentration (a chemical waste product produced by your muscle).

•Increased blood urea concentration (a chemical waste product).

•Fever.

•Fatigue.

Common:

•Bleeding (hemorrhage).

•Metabolic disorder caused by cancer cells dying, which release their contents into the bloodstream.

•Decreased red blood cells, which can cause pale skin and cause weakness or difficulty breathing (anemia).

•Low neutrophil counts (a common type of white blood cell needed to fight infections).

•Allergic reactions, such as skin inflammation (dermatitis) or urticaria.

•Elevated liver enzymes AST/ALT (may indicate liver inflammation or damage).

•Increased alkaline phosphatase enzyme (an enzyme synthesized mainly in the liver and bones).

•Increased bilirubin pigment (a substance produced during the normal breakdown of red blood cells).

•Low potassium blood levels (a nutrient needed for nerve and muscle cell function, including heart cells).

•Cardiac dysfunction.

•Abnormal heart rhythm (arrhythmia).

•Increased or decreased blood pressure (hypotension or hypertension).

•Pulmonary function disorder.

•Diarrhea.

•Constipation.

•Mouth ulcers (stomatitis).

•Loss of appetite.

•Hair loss.

•Cutaneous alterations.

•Amenorrhea (absence of menstruation).

•Pain.

•Insomnia.

•Chills.

•Dehydration.

•Vertigo.

Uncommon:

•Accumulation of fluid in the sac that surrounds the heart (pericardial effusion).

•Ineffective production of all blood cells in the bone marrow (spongy tissue inside the bones where blood cells are generated).

•Acute leukemia.

•Myocardial infarction, chest pain (myocardial infarction).

•Heart failure.

Rare:

•Blood infection (sepsis).

•Severe allergic and hypersensitivity reactions (anaphylactic reactions).

•Bone marrow dysfunction, which may cause you to feel unwell or appear in your blood test results.

•Similar symptoms to anaphylactic reactions (anaphylactoid reactions).

•Drowsiness.

•Loss of voice (aphonia).

•Acute circulatory failure (circulatory failure primarily of cardiac origin with inability to maintain oxygen and nutrient supply to tissues and elimination of toxins).

•Redness of the skin (erythema).

•Skin inflammation (dermatitis).

•Itching (pruritus).

•Maculopapular rash.

•Excessive sweating (hyperhidrosis).

Very rare:

•Atypical primary pulmonary inflammation (pneumonia).

•Red blood cell destruction.

•Rapid drop in blood pressure, sometimes with skin reactions (anaphylactic shock).

•Alteration of taste.

•Alteration of sensitivity (paresthesias).

•Discomfort and pain in the extremities (peripheral neuropathy).

•Severe condition that causes the blockade 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 (esophagitis).

•Gastrointestinal or intestinal hemorrhage.

•Infertility.

•Multi-organ failure.

Frequencynot known

•Liver failure.

•Renal failure.

•Irregular and often rapid heartbeats (atrial fibrillation).

•Widespread painful 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).

•Exanthema medicamentosa in combination therapy with rituximab.

•Pneumonitis.

•Pulmonary hemorrhage.

•Excessive urination, even at night, and excessive thirst, even after drinking liquids (nephrogenic diabetes insipidus).

There have been reports of tumors (myelodysplastic syndromes, acute myeloid leukemia, bronchial carcinoma) after treatment withhydrochloride bendamustine. A clear relationship withhydrochloride bendamustinecould not be established.

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

Severe skin eruptions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. These may appear as red, target-like spots, or circular patches with central blisters on the torso, 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).

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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 carton after CAD. The expiration date is the last day of the month indicated.

The vials may be packaged with or without a plastic protective wrapper.

Verify the expiration period before opening or preparing the solution.

Chemical and physical stability has been demonstrated for use during 3.5 hours at 25°C and up to 48 hours at 2-8°C in polyethylene bags.

From a microbiological standpoint, the medication should be used immediately. If not used immediately, storage times and conditions before use are the responsibility of the user and should normally not exceed 24 hours at 2°C-8°C, unless reconstitution and dilution have taken place in controlled and validated aseptic conditions.

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

Composition of Bendamustine Aurovitas

-The active ingredient is bendamustine hydrochloride.

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

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

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

-The other component is mannitol.

Appearance of the product and packaging size

Concentrate powder for solution for infusion.

White or off-white lyophilized powder.

Tube-shaped glass vials type I of topaz color of 20 ml with a 20 mm neck, closed with a grey bromobutyl rubber stopper of 20 mm and sealed with an aluminum cap with a polipropylene disc.

Tube-shaped glass vials type I of topaz color of 50 ml with a 20 mm neck, closed with a grey bromobutyl rubber stopper of 20 mm and sealed with an aluminum cap with a polipropylene disc.

Bendamustine Aurovitas is available in packaging containing 1, 5, 10 and 20 vials with 25 mg of bendamustine hydrochloride and 1, 5 and 10 vials with 100 mg of bendamustine hydrochloride.

Only some packaging sizes may be marketed.

Marketing Authorization Holder and Responsible for Manufacturing

Marketing Authorization Holder

Eugia Pharma (Malta) Limited

Vault 14, Level 2, Valletta Waterfront

Floriana, FRN 1914

Malta

Responsible for Manufacturing

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

O

Generis Farmacêutica, S.A.

Rua João de Deus, nº 19, Venda Nova

2700-487 Amadora

Portugal

O

Arrow Génériques

26 Avenue Tony Garnier

69007 Lyon

France

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

This medicine is authorized in the member states of the European Economic Area with the following names:

Germany:Bendamustin PUREN 2.5 mg/ml Powder for the preparation of a concentrate for the preparation of an infusion solution

Belgium:Bendamustine Eugia2.5 mg/ml powder for concentrate for solution for infusion / powder for solution to be diluted for perfusion / Pulver for a concentrate for the preparation of an infusion solution

Spain:Bendamustine Aurovitas 2.5 mg/mlpowder for concentrate for solution for infusion EFG

France:BENDAMUSTINE ARROW 2.5 mg/ml, powder for solution to be diluted for perfusion

Italy:BendamustineAurobindo

Portugal:BendamustineGeneris

Poland:Bendamustine Eugia

Last review date of this leaflet:March 2024

The detailed information about this medicine 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 healthcare professionals:

As with all similar cytotoxics, healthcare personnel and doctors must exercise extreme caution due to the potential genotoxicity and carcinogenicity of the preparation. Avoid inhalation (respiration) and contact with the skin and mucous membranes while handling this medicine (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. Contaminated items are cytostatic waste. Follow national regulations for the disposal of cytostatic material. Women personnel who are pregnant should not work with cytotoxics.

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

1.Preparation of the concentrate

•First, dissolve a vial of Bendamustine Aurovitas containing 25 mg of bendamustine hydrochloride in 10 ml, shaking it.

•First, dissolve a vial of Bendamustine Aurovitas containing 100 mg of bendamustine hydrochloride in 40 ml, shaking it.

2.Preparation of the infusion solution

Nothing more than a transparent solution (usually within 5 to 10 minutes) should be dissolved in isotonic saline solution (0.9%) to obtain a final volume of approximately 500 ml. Bendamustine Aurovitas should not be dissolved with other infusion or injection solutions. Bendamustine Aurovitas should not be mixed with other substances during perfusion.

3.Administration

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

The vials are for single use.

The elimination 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 (extravascular injection), the perfusion 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 raised. It is not clear that the use of additional treatments (such as corticosteroids) is beneficial (see section 4).