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

Bendamustine, hydrochloride

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, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

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

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

Bendamustine 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 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 Aurovitas

Do not use Bendamustina Aurovitas

• if you are allergic to bendamustine hydrochloride or to any of the other ingredients of this medicine (listed in section 6).
• during breastfeeding; if you require treatment with bendamustine hydrochloride while 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 a severe bone marrow disorder (bone marrow suppression) and serious 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, pharmacist, or nurse before starting treatment with bendamustine.

• if your bone marrow’s ability to replace blood cells is reduced. The number of white blood cells and platelets in your blood should be measured before starting treatment with bendamustine hydrochloride, before each treatment cycle, and between cycles.
• if you have infections. If you develop signs of infection, such as fever or respiratory symptoms, contact your doctor.
• if you develop skin reactions during treatment with bendamustine hydrochloride. Skin reactions may increase in severity.
• if you develop widespread, painful red or purple rashes, blisters, and/or other lesions starting in the mucous membranes (e.g., mouth and lips), especially if you have previously had light sensitivity, respiratory infections (e.g., bronchitis), and/or fever.
• if you have heart disease (e.g., heart attack, chest pain, serious heart rhythm disorders).
• if you experience pain in your side or notice blood in your urine or reduced urine output. If your condition is severe, your body may be unable to eliminate waste products from dying cancer cells. This is called tumor lysis syndrome and may lead to kidney failure and heart problems within 48 hours after the first dose of bendamustine hydrochloride. 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-related 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 vision loss. These symptoms may be due to a very rare but serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML).
• contact your doctor if you notice any suspicious changes in your skin, as use of this medicine may increase the risk of certain types of skin cancer (non-melanoma skin cancer).

Other medicines and Bendamustina Aurovitas

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

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

If bendamustine hydrochloride 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

Bendamustine hydrochloride can cause genetic damage and has caused birth defects in animal studies. This medicine 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 bendamustine hydrochloride. If you become pregnant during treatment with bendamustine hydrochloride, inform your doctor immediately and seek genetic counselling.

Breastfeeding

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

Consult your doctor or pharmacist before using any medicine.

Fertility

If you are a man, you must not father a child during treatment with bendamustine hydrochloride and for up to 6 months after treatment. There is a risk that treatment with bendamustine hydrochloride may cause infertility; you may wish to seek advice about sperm preservation before starting treatment.

Driving and using machines

Bendamustine hydrochloride has a major influence 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 Bendamustine Aurovitas

Follow exactly the instructions for administration of this medicine given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

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 (leucocyte) and/or platelet count is below the determined levels.

Your doctor will measure these values periodically.

Chronic lymphocytic leukaemia

Non-Hodgkin lymphomas

Multiple myeloma

Treatment will be discontinued if the white blood cell (leucocyte) count and/or platelet count falls below the predetermined levels. Treatment may be resumed when the leucocyte and platelet counts have increased.

Renal or hepatic impairment

Dosage adjustment may be necessary depending on the degree of liver function impairment (initial reduction by 30% in case of moderate liver impairment). No dosage adjustment is required in case of impaired kidney function. Your doctor will decide whether dosage adjustment is necessary.

How it is administered

Bendamustine hydrochloride can only be administered by physicians experienced in the treatment of tumours. Your doctor will administer the exact dose of bendamustine hydrochloride 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 bendamustine hydrochloride 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 bendamustine hydrochloride, speak with your doctor or nurse.

If you forget to use Bendamustina Aurovitas

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

If you interrupt treatment with Bendamustina Aurovitas

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 may produce adverse effects, although not everyone experiences them. Some of the findings listed below may be detected following tests performed by your doctor.

The following definitions are used to evaluate adverse effects, based on their frequency:

In very rare cases, tissue degradation (necrosis) has been observed following extravasation of bendamustine hydrochloride into the tissue surrounding blood vessels (extravascular). If the product leaks outside a blood vessel, a burning sensation may occur at the needle insertion site. Consequences may include pain and impaired skin healing.

The dose-limiting adverse effect of bendamustine hydrochloride is bone marrow function impairment, which is usually reversible. Suppression of bone marrow function may lead to reduced blood cell counts, thereby increasing the risk of infection, anemia, or increased risk of bleeding.

Very common:

• Low white blood cell counts (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).
• Low platelet counts (colorless blood cells that help blood clotting).
• Infections.
• Nausea.
• Vomiting.
• Mucosal 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 disturbances caused by dying cancer cells releasing their contents into the bloodstream.
• Decrease in red blood cells, which may cause pale skin and lead to weakness or difficulty breathing (anemia).
• Low neutrophil counts (a common type of white blood cell needed to fight infections).
• Hypersensitivity reactions, such as allergic skin inflammation (dermatitis) or hives.
• Elevation of liver enzymes AST/ALT (may indicate inflammation or damage to liver cells).
• Increased alkaline phosphatase enzyme (an enzyme mainly produced in the liver and bones).
• Increase in bile pigment (a substance produced during normal breakdown of red blood cells).
• Decreased blood potassium levels (a nutrient necessary for nerve and muscle cell function, 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 (fluid leakage into the pericardial space).
• Ineffective production of all blood cells in the bone marrow (spongy tissue inside bones where blood cells are generated).
• Acute leukemia.
• Heart attack, chest pain (myocardial infarction).
• Heart failure.

Rare:

• 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 resembling anaphylactic reactions (anaphylactoid reactions).
• Drowsiness.
• Loss of voice (aphonia).
• Acute circulatory failure (failure of blood circulation primarily of cardiac origin, with inability to maintain oxygen and other nutrients supply to tissues and toxin elimination).
• Skin redness (erythema).
• Skin inflammation (dermatitis).
• Itching (pruritus).
• Skin rash (maculopapular exanthema).
• Excessive sweating (hyperhidrosis).

Very rare:

• Primary atypical lung inflammation (pneumonia).
• Destruction of red blood cells in the blood.
• Rapid drop in blood pressure, sometimes with skin reactions or rashes (anaphylactic shock).
• Altered sense of taste.
• Altered sensation (paresthesia).
• Discomfort and pain in limbs (peripheral neuropathy).
• Serious condition causing blockade of specific receptors in the nervous system.
• Disorders of the nervous system.
• Lack of coordination (ataxia).
• Brain inflammation (encephalitis).
• Increased heart rate (tachycardia).
• Vein inflammation (phlebitis).
• Tissue formation in the lungs (pulmonary fibrosis).
• Hemorrhagic inflammation of the throat (hemorrhagic esophagitis).
• Gastric or intestinal bleeding.
• Infertility.
• Multi-organ failure.

Frequency not known:

• Liver failure.
• Kidney failure.
• Irregular and often rapid heartbeats (atrial fibrillation).
• Painful, widespread red or purple rashes and blisters and/or other lesions beginning to appear on mucous membranes (e.g., mouth and lips), especially 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 tumors (myelodysplastic syndromes, acute myeloid leukemia, bronchial carcinoma) after treatment with bendamustine hydrochloride. A clear relationship with bendamustine hydrochloride 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 reddish spots resembling targets, or circular lesions often with central blisters on the trunk, skin peeling, mouth, throat, nose, genital or 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 adverse reactions

If you experience any adverse reaction, consult your doctor or pharmacist, even if it is a possible adverse reaction 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 reactions, you can help provide more information on the safety of this medicine.

5. Storage of Bendamustine Aurovitas

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

Vials may be packaged with or without a protective plastic overwrap.

Check the expiry date before opening or preparing the solution.

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

From a microbiological standpoint, the medicine should be used immediately. If not used immediately, the storage times and conditions prior to 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 under controlled and validated 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. This will help protect the environment.

6. Contents of the pack and other information

Composition of Bendamustine Aurovitas

• The active substance is bendamustine hydrochloride.

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

Presentation of the product and pack sizes

Powder for concentrate for solution for infusion.

White or almost white lyophilized powder or paste.

Type I amber glass vials of 20 ml with 20 mm neck, closed with a grey bromobutyl rubber stopper of 20 mm and sealed with an aluminum cap with a polypropylene disc.

Type I amber glass vials of 50 ml with 20 mm neck, closed with a grey bromobutyl rubber stopper of 20 mm and sealed with an aluminum cap with a polypropylene disc.

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

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Eugia Pharma (Malta) Limited
Vault 14, Level 2, Valletta Waterfront
Floriana, FRN 1914
Malta

Manufacturer

APL Swift Services (Malta) Limited
HF26, Hal Far Industrial Estate, Hal Far
Birzebbugia, BBG 3000
Malta

Or

Generis Farmacêutica, S.A.
Rua João de Deus, nº 19, Venda Nova
2700-487 Amadora
Portugal

Or

Arrow Génériques
26 Avenue Tony Garnier
69007 Lyon
France

Further information on this medicinal product is available from the local representative of the Marketing Authorization Holder:

Aurovitas Spain, S.A.U.
Avda. de Burgos, 16-D
28036 Madrid
Spain

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

Germany: Bendamustin PUREN 2,5 mg/ml Pulver zur Herstellung eines Konzentrates zur Herstellung einer Infusionslösung

Belgium: Bendamustine Eugia 2,5 mg/ml poeder voor concentraat voor oplossing voor infusie / poudre pour solution à diluer pour perfusion / Pulver für ein Konzentrat zur Herstellung einer Infusionslösung

Spain: Bendamustina Aurovitas 2,5 mg/ml polvo para concentrado para solución para perfusión EFG

France: BENDAMUSTINE ARROW 2,5 mg/ml, poudre pour solution à diluer pour perfusion

Italy: Bendamustina Aurobindo

Portugal: Bendamustina Generis

Poland: Bendamustine Eugia

Date of the most recent revision of this leaflet: March 2024

Detailed information on this medicinal product 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 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% isotonic saline solution. If possible, it is recommended to work on a specialized safety cabinet (laminar flow hood) using a liquid-proof disposable absorbent pad. Contaminated materials are cytostatic waste. Follow national regulations regarding the disposal of cytostatic material. Pregnant healthcare workers should not handle cytostatics.

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

1. Preparation of the concentrate

   • First, dissolve the contents of one vial of Bendamustine Aurovitas containing 25 mg of bendamustine hydrochloride in 10 ml, with agitation.
   • First, dissolve the contents of one vial of Bendamustine Aurovitas containing 100 mg of bendamustine hydrochloride in 40 ml, with agitation.

2. Preparation of the infusion solution

Immediately after obtaining a clear solution (usually within 5 to 10 minutes), dilute the recommended total dose of bendamustine in 0.9% isotonic saline solution to achieve a final volume of approximately 500 ml. Bendamustine Aurovitas must not be dissolved in other infusion or injection solutions. Bendamustine Aurovitas 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.

Disposal of unused medicinal product and of all materials that have been in contact with it must be carried out in accordance with local regulations.

If extravasation (accidental injection into the tissue surrounding blood vessels) occurs, the infusion must be stopped immediately. The needle should be withdrawn after brief aspiration. The affected tissue area should then be cooled and the arm elevated. It is unclear whether additional treatments (such as corticosteroids) are beneficial (see section 4).