BENDAMUSTINA 2.5 mg/ml Powder for concentrate and solution for infusion

Зміст інструкції

1. Bendamustina Dr. Reddy’s 2.5 mg/ml powder for concentrate for solution for infusion
   1. How to store Bendamustina Dr. Reddy’s

Bendamustina Dr. Reddy’s 2.5 mg/ml powder for concentrate for solution for infusion

Equivalen medicine
Read this leaflet carefully before you use this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1What is Bendamustina Dr. Reddy’sand what it is used for
Bendamustina is a medicine used for the treatment of certain types of cancer (cytotoxic
medicine).
Bendamustina is used alone (monotherapy) or in combination with other medicines for the
treatment of the following forms of cancer:

• chronic lymphocytic leukemia in cases where chemotherapeutic combination with fludarabine is not appropriate for you,
• Non-Hodgkin lymphomas, which have not responded, or have responded only briefly to previous treatment with rituximab,
• multiple myeloma, in cases where high-dose chemotherapy treatment integrated with autologous stem cell transplantation or a therapeutic regimen based on thalidomide or bortezomib are not appropriate for you.

2What you need to know before you use Bendamustina Dr. Reddy’s
Do not use Bendamustina Dr. Reddy’s:

• 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 bendamustine is necessary during breastfeeding, you must stop breastfeeding (see section warnings and precautions regarding breastfeeding);
• if you have severe hepatic insufficiency (damage to the functional cells of the liver);

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• if your skin or the whites of your eyes are yellow due to liver or blood problems (jaundice);
• if you have severe impairment of bone marrow function (bone marrow depression) and significant changes in the number of white blood cells and platelets in the blood;
• if you have undergone major surgery less than thirty days before the start of treatment;
• if you have an infection, especially if it is accompanied by a decrease in white blood cells (leukopenia);
• in combination with the yellow fever vaccine.

Warnings and precautions
Talk to your doctor or nurse before using Bendamustina Dr. Reddy’s.

• in case of reduced ability of the bone marrow to regenerate blood cells. You must check your white blood cell and platelet count before starting treatment with Bendamustina Dr. Reddy’s, before each subsequent treatment cycle and in the intervals between the various treatment cycles;
• in case of infection. You should contact your doctor if you show symptoms of infection, including fever or lung symptoms;
• in case of pre-existing heart disease(e.g. heart attack, chest pain, severely disturbed heart rhythm).

Talk to your doctor or nurse during the use of Bendamustina Dr. Reddy’s

• if you notice any type of flank pain, blood in your urine or a reduced amount ofurine. When your illness is very serious, your body may not be able to eliminate all the waste products resulting from the death of cancer cells. This is called "tumor lysis syndrome" and can cause kidney failure and heart problems within 48 hours of the first dose of Bendamustina Dr. Reddy’s. Your doctor will be able to ensure that you are adequately hydrated and may give you other medicines to try to prevent it;
• in case of skin reactionsduring treatment with Bendamustina Dr. Reddy’s. The severity of the reactions may increase;
• in case of painful red or purple rash that spreads and forms blisters and/or other lesions that begin to appear on the mucous membrane (e.g. the mouth and lips), especially if you have previously had sensitivity to light, respiratory infections (e.g. bronchitis) and/or fever
• in case of severe allergic reaction or hypersensitivity reactions. You should pay attention to infusion reactions that have occurred after your first cycle of therapy.

Children and adolescents
There is no experience of the use of bendamustine hydrochloride in children and adolescents.

Other medicines and Bendamustina Dr. Reddy’s
Tell your doctor or pharmacistif you are taking, have recently taken or might take
any other medicines.
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If Bendamustina Dr. Reddy’s is taken in combination with medicines that inhibit the formation
of blood cells in the bone marrow, the effect on the bone marrow may be intensified.
If Bendamustina Dr. Reddy’s is taken in combination with medicines that alter your
immune response, this effect may be intensified.
Cytostatic medicines can decrease the effectiveness of vaccination with live viruses. Additional
cytostatic medicines increase the risk of infection after vaccination with live vaccines (e.g.
antiviral vaccination).

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant or are planning to become pregnant, or if you are
breastfeeding, ask your doctor or pharmacist for advice before using this medicine.
Pregnancy
Bendamustina Dr. Reddy’s may cause genetic damage and has caused malformations in studies on
animals. You must not use Bendamustina Dr. Reddy’s during pregnancy unless clearly prescribed by
your doctor. In case of treatment, you should consult a doctor about the potential risk of adverse effects
on the unborn child, and genetic counseling is recommended.
If you are a woman of childbearing potential, you should use effective contraception
both before and during treatment with Bendamustina Dr. Reddy’s. If pregnancy occurs
during treatment with Bendamustina Dr. Reddy’s, you should immediately inform your doctor and
have genetic counseling.
If you are a man, you should avoid fathering a child during treatment with Bendamustina Dr. Reddy’s
and for up to 6 months after the end of treatment. There is a risk that treatment with Bendamustina
Dr. Reddy’s may lead to infertility, and you may benefit from counseling on sperm preservation
before treatment begins.
Breastfeeding
Bendamustina Dr. Reddy’s must not be administered during breastfeeding. If treatment with
Bendamustina Dr. Reddy’s is necessary during breastfeeding, you must stop
breastfeeding. Ask your doctor or pharmacist for advice before taking any
medicine.
Fertility
Men undergoing treatment with Bendamustina Dr. Reddy’s are advised not to father children
during treatment and for 6 months after treatment. Before starting treatment, you may
ask for advice on sperm preservation because there is a possibility of permanent infertility.

Driving and using machines
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Studies have not been conducted on the ability to drive and use machines. Do not drive or operate
machinery if you experience side effects such as dizziness or lack of coordination.

3How to use Bendamustina Dr. Reddy’s
Bendamustina Dr. Reddy’s is administered intravenously over 30 – 60 minutes at various dosages, alone
(monotherapy) or in combination with other medicines.
Treatment should not be started if your white blood cell count (leukocytes) has fallen below
certain levels.
The doctor will check these values at regular intervals
Chronic lymphocytic leukemia
Non-Hodgkin lymphoma
Multiple myeloma
Treatment should be stopped if the values of white blood cells (leukocytes) and/or platelets
fall to certain values.
Renal or hepatic impairment
Depending on the degree of impairment of your liver function, your
dose may need to be adjusted (by 30% in case of moderate hepatic dysfunction). No dose adjustment is
necessary in case of renal impairment.
The doctor will decide whether a dosage adjustment is necessary.

How it is administered
Treatment with Bendamustina Dr. Reddy’s must only be carried out by doctors experienced in cancer
therapy. The doctor will give you the exact dose of Bendamustina Dr. Reddy’s, using the necessary
precautions.

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The doctor will administer the solution for infusion after preparation as prescribed. The solution
is administered intravenously with a brief infusion lasting 30 – 60 minutes.

Duration of therapy
There is no time limit foreseen as a general rule for treatment with Bendamustina Dr.
Reddy’s. The duration of treatment depends on the disease and the response to treatment.
If you are worried or have any questions about treatment with Bendamustina Dr. Reddy’s, talk
to your doctor or nurse.

If you forget to use Bendamustina Dr. Reddy’s.
If a dose of Bendamustina Dr. Reddy’s has been forgotten, the doctor will usually maintain the normal
dosing schedule

If you stop using Bendamustina Dr. Reddy’s.
The doctor will decide whether to stop treatment or switch to a different preparation.
If you have any doubts about using this medicine, talk to your doctor or pharmacist.

4Possible side effects
Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Some of these effects listed below may be detected after tests performed by your doctor.
Necrotic tissues (necrosis) have been observed very rarely following leakage of bendamustine
into the tissue outside the blood vessels (extravasation). A burning sensation where the
infusion needle was inserted may be a sign of leakage from the blood vessels. Consequently, pain and
skin defects due to poor healing may occur.
The side effect of Bendamustina Dr. Reddy’s that limits its dosage is impairment
of bone marrow function, which generally returns to normal after treatment. Suppression
of bone marrow function can lead to a reduction in blood cells, which in turn
may lead to an increased risk of infection, anemia, or an increased risk of
bleeding.
Very common side effects (which can affect more than 1 in 10 people)
Low number of white blood cells (cells in your blood that fight disease) • decrease in
red blood pigment (hemoglobin: a protein in red blood cells that carries oxygen
in the body) • low number of platelets (cells in the blood that help blood clotting)
• infections • feeling unwell (nausea) • vomiting • inflammation of the mucous membranes • headache • increased creatinine levels in the blood (a waste substance produced by muscles) •
increased urea levels in the blood (a waste chemical) • fever • fatigue
Common side effects (which can affect up to 1 in 10 people)
Bleeding (hemorrhage) • metabolic disorders caused by the death of cancer cells that
release their contents into the bloodstream • reduction of red blood cells, which can determine
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paleness of the skin and cause weakness or shortness of breath (anemia) • low number of neutrophils (a type of
white blood cells important for fighting infections) • hypersensitivity reactions such as
allergic skin inflammation (dermatitis) and rash (urticaria)• increased liver enzymes
AST/ALT (indicating inflammation or damage to liver cells) • increased alkaline phosphatase enzyme (an enzyme produced mainly by the liver and bones) • increased bile pigment
(a substance produced during the normal breakdown of red blood cells) • low potassium levels in
the blood (a nutrient necessary for the function of nerve and muscle cells, including those of the
heart) • altered cardiac function (palpitations, angina pectoris) • heart rhythm disturbances (arrhythmia) • low or high blood pressure (hypotension or hypertension) • altered
lung function • diarrhea • constipation • ulceration of the mouth (stomatitis) • loss of appetite •
hair loss • skin changes • cessation of menstruation (amenorrhea) • pain •
insomnia • chills • dehydration • dizziness• itching (urticaria)
Uncommon side effects (can affect up to 1 in 100 people)
Fluid accumulation in the pericardial sac (pericardial effusion) • deficiency
in the production of all blood cells (myelodysplastic syndrome) • acute leukemia •heart attack, chest pain (myocardial infarction) • heart failure
Rare side effects (can affect up to 1 in 1000 people)
Blood infections (sepsis) • severe allergic hypersensitivity reactions (anaphylactic reactions) •
reduction in bone marrow function, which can make you feel unwell or appear in
blood tests • signs similar to anaphylactic reactions (anaphylactoid reactions) • drowsiness • loss of
voice (aphonia) • acute circulatory collapse (circulatory deficiency primarily of cardiac origin
with inability to supply oxygen or other nutrients to tissues and removal of toxins) • redness of
the skin (erythema) • skin inflammation (dermatitis) • itching • rash (macular rash)

• excessive sweating (hyperhidrosis)

Very rare side effects (can affect up to 1 in 10,000 people)
Primary atypical inflammation of the lungs (pneumonia) • rupture of red blood cells • rapid
decrease in blood pressure sometimes with reaction and rash (anaphylactic shock) •
altered sense of taste • altered sensations (paresthesia) • discomfort and pain in the limbs
(peripheral neuropathy) • severe condition resulting from the blockage of specific receptors in the
nervous system • nervous system disorders • lack of coordination (ataxia) • inflammation of the
brain (encephalitis) • increased heart rate (tachycardia) • inflammation of the veins (phlebitis) •
formation of tissue in the lungs (pulmonary fibrosis) • inflammation of the esophagus associated with
bleeding (hemorrhagic esophagitis) • bleeding from the stomach or intestines • infertility •
multiple organ failure
Side effects with unknown frequency(frequency cannot be estimated based on available data)
Liver failure • kidney failure • irregular and often rapid heart rate (atrial fibrillation) • painful red or purple rash that spreads and forms blisters and/or other lesions
that begin to appear on the mucous membrane (e.g. mouth and lips), especially
if previously sensitive to light, respiratory system infections (e.g. bronchitis)
and/or fever • pneumonia • bleeding from the lungs
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Cases of tumors (myelodysplastic syndrome, acute myeloid leukemia, bronchial carcinoma) have been reported following treatment with Bendamustina Dr. Reddy’s. A clear relationship with Bendamustina Dr. Reddy’s has not been determined.

Contact your doctor or seek immediate medical attentionif you notice any of the
following side effects:

• Severe skin rashes including Stevens-Johnson syndrome and toxic epidermal necrolysis. These can manifest as reddish macules or circular spots often with central blisters on the trunk, skin peeling, ulcers of the mouth, throat, nose, genitals and eyes and may be preceded by fever and flu-like symptoms.
• Widespread rash, high body temperature, enlarged lymph nodes and involvement of other organs (Drug Reaction with Eosinophilia and Systemic Symptoms also known as DRESS or drug hypersensitivity syndrome).

Reporting of side effects
If you get any side effect, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through
the national reporting system at www.agenziafarmaco.gov.it/content/come-segnalare-
una-sospetta-reazione-avversa. By reporting side effects you can help provide more
information on the safety of this medicine.

5. How to store Bendamustina Dr. Reddy’s

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and the label after
“Exp.”. The first two digits indicate the month and the last four digits indicate the year. The date of
expiry refers to the last day of that month.
Keep the container in the box to protect the medicine from light.

Notes on the period of validity after opening or preparation of the solution
Bendamustina Dr. Reddy’s does not contain preservatives.
After reconstitution and dilution, chemical and physical stability has been demonstrated for 3.5 hours at 25°C/60%
RH and for 2 days between 2°C and 8°C in polyethylene bags.
From a microbiological point of view, the diluted solution must be used immediately. If not
used immediately, the storage times during use and the conditions prior to use are
the responsibility of the user and should normally not be longer than 24 hours between 2°C and
8°C, unless the reconstitution/dilution has taken place under controlled and validated aseptic conditions.
Do not dispose of any medicine in the drain or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.
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6Contents of the pack and other information
What contains Bendamustina Dr. Reddy’s

• The active ingredient is bendamustine hydrochloride. 1 vial contains 25 mg of bendamustine hydrochloride 1 vial contains 100 mg of bendamustine hydrochloride After reconstitution 1 ml of concentrate contains 2.5 mg of bendamustine hydrochloride.
• The other ingredient is mannitol.

Description of the appearance of Bendamustina Dr. Reddy’s and contents of the pack
Lyophilized powder of white to off-white color in an amber glass vial closed with a
rubber stopper and aluminum crimp cap with a flip-top.
Bendamustina Dr. Reddy’s is available in packs of 1, 5, 10 and 20 vials of 25 ml with 25 mg
of bendamustine hydrochloride and 1 or 5 vials of 50 ml with 100 mg of bendamustine hydrochloride.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:
DR. REDDY'S S.R.L.
PIAZZA SANTA MARIA BELTRADE, 1, 20123 – MILAN (MI)

Manufacturer:
Synthon Hispania SL
C/Castelló no 1, Pol. Las Salinas, Sant Boi de Llobregat
Barcelona 08830 Spain
Synthon s.r.o.
Brnĕnská 32/čp. 597
Blansko 678 01 Czech Republic
Dr. Reddy’s Laboratories (UK) Ltd
6 Riverview Road, Beverley, East Yorkshire
United Kingdom
betapharm Arzneimittel GmbH
Kobelweg 95
86156 Augsburg
Germany
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This medicinal product is authorised in the Member States of the European Economic Area with the
following denominations:
France Bendamustine Dr. Reddy´s 2,5 mg/ml, poudre pour solution à diluer pour
perfusion
Germany Bendamustin HCl beta 2,5 mg/ml Pulver für ein Konzentrat zur Herstellung
einer Infusionslösung
Italy Bendamustina Dr. Reddy's
Spain Bendamustina, clorhidrato Dr. Reddy´s 2,5 mg/ml polvo para concentrado para
solución para perfusión EFG
United Kingdom Bendamustine hydrochloride 2.5 mg/ml Powder for concentrate for solution for
infusion

The following information is intended exclusively for physicians or healthcare professionals:
As with all similar cytotoxic substances, strict safety measures must be adopted
regarding nursing and medical personnel involved, due to the potential carcinogenic and genetic damage effects of the preparation.
Avoid inhalation (by aspiration) and contact with skin and mucous membranes when handling
bendamustine (wear gloves, protective clothing and possibly a mask!). If any
part of the body becomes contaminated, clean it thoroughly with water and soap, and rinse the eyes
with 0.9% (isotonic) saline solution. If possible, it is recommended to work on a suitable work
surface (laminar flow), with a disposable waterproof absorbent sheet.
Contaminated items must be considered cytotoxic waste. Please observe the national guidelines on the disposal of cytotoxic material!
Pregnant personnel must be excluded from working with cytostatic agents.
The ready-to-use solution must be prepared by dissolving the contents of one injection vial of
bendamustine exclusively in water for injections, as described below:

• 1. Preparation of the concentrate
• One vial of bendamustine containing 25 mg of bendamustine hydrochloride and first dissolved in 10 ml, shaking the solution;
• One vial of bendamustine containing 100 mg of bendamustine hydrochloride and first dissolved in 40 ml, shaking the solution.
• 2. Preparation of the infusion solution As soon as a clear solution is obtained (usually after 5 – 10 minutes), the recommended total dose of bendamustine is immediately diluted with 0.9% saline (isotonic) to obtain a final volume of approximately 500 ml. Bendamustine must not be diluted with other infusion or injection solutions. Bendamustine must not be mixed with infusions containing other substances.
• 3. Administration The solution is administered by intravenous infusion over 30-60 minutes.

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The vials are for single use only.
Unused medicine and waste material from this medicine must be disposed of in
accordance with local regulations.
Any involuntary injection into the tissue outside the blood vessels (extravasation) must be
immediately stopped. The needle must be removed after brief aspiration. After
this, the affected tissue area must be cooled. The arm must be elevated. Additional treatments such as the use of corticosteroids do not lead to clear benefits (see section 4).
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